Trial Outcomes & Findings for Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients (NCT NCT03280056)

Last Updated: 2024-02-29

Results Overview

The ALSFRS-R is a quickly administered (10 minutes) ordinal, validated rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, as measured by quantitative neuromuscular strength testing, and with quality of life measures, and predicted survival. The total score of ALSFRS-R ranges from 0-48, with higher score being better.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

196 participants

Primary outcome timeframe

28 weeks following the first intrathecal injection

Results posted on

2024-02-29

Participant Flow

The first participant in Study BCT-002-US signed informed consent on 28 August 2017 The last participant visit took place on 29 September 2020. The study was conducted at 6 clinical sites in the USA. A total of 263 participants were screened for the study, and 196 participants (74.5% of participants screened) were randomly assigned (1:1) to treatment with either NurOwn or placebo.

The most common reasons that participants did not meet inclusion criteria were failure to meet the SVC inclusion criterion at the Screening Visit or the required pre-treatment decline in ALSFRSR total score at the randomization visit. From the ITT population, 3 participants in the NurOwn group and 4 participants in the placebo group discontinued prior to treatment.

Participant milestones

Participant milestones
Measure	NurOwn® (MSC-NTF Cells) NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10'6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors Bone marrow aspiration	Placebo One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection Bone marrow aspiration
Overall Study STARTED	95	94
Overall Study COMPLETED	71	73
Overall Study NOT COMPLETED	24	21

Reasons for withdrawal

Reasons for withdrawal
Measure	NurOwn® (MSC-NTF Cells) NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10'6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors Bone marrow aspiration	Placebo One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection Bone marrow aspiration
Overall Study Withdrawal by Subject	12	14
Overall Study Death	9	2
Overall Study Adverse Event	1	3
Overall Study Lost to Follow-up	1	1
Overall Study Physician Decision	0	1
Overall Study Early Discontinuation	1	0

Baseline Characteristics

Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NurOwn® (MSC-NTF Cells) n=95 Participants NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10'6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors Bone marrow aspiration	Placebo n=94 Participants One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection Bone marrow aspiration	Total n=189 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	95 Participants n=99 Participants	94 Participants n=107 Participants	189 Participants n=206 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Continuous Mean	48.1 years STANDARD_DEVIATION 9.71 • n=99 Participants	49.1 years STANDARD_DEVIATION 8.38 • n=107 Participants	48.6 years STANDARD_DEVIATION 9.07 • n=206 Participants
Sex: Female, Male Female	27 Participants n=99 Participants	35 Participants n=107 Participants	62 Participants n=206 Participants
Sex: Female, Male Male	68 Participants n=99 Participants	59 Participants n=107 Participants	127 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=99 Participants	3 Participants n=107 Participants	8 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	90 Participants n=99 Participants	91 Participants n=107 Participants	181 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	5 Participants n=99 Participants	7 Participants n=107 Participants	12 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Black or African American	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) White	87 Participants n=99 Participants	81 Participants n=107 Participants	168 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Region of Enrollment United States	95 participants n=99 Participants	94 participants n=107 Participants	189 participants n=206 Participants
Baseline Amyotrophic Lateral Sclerosis Functional Rating ScaleScore	30.3 units on a scale STANDARD_DEVIATION 6.5 • n=99 Participants	31.4 units on a scale STANDARD_DEVIATION 6.1 • n=107 Participants	30.9 units on a scale STANDARD_DEVIATION 6.3 • n=206 Participants

PRIMARY outcome

Timeframe: 28 weeks following the first intrathecal injection

Population: The modified intent-to-treat (mITT) population was defined as all participants who were randomized, treated and had at least three ALSFRS-R assessments: one pre-treatment assessments of ALSFRS-R prior to the baseline assessment, a baseline assessment and one post-treatment assessment.

Outcome measures

Outcome measures
Measure	NurOwn® (MSC-NTF Cells) n=95 Participants NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10'6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors Bone marrow aspiration	Placebo n=94 Participants One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection Bone marrow aspiration
The Proportion of NurOwn® Treated Participants With a ≥1.25 Points/Month Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score at 28 Weeks Following the First Treatment as Compared to Placebo YES (%)	31 Participants	26 Participants
The Proportion of NurOwn® Treated Participants With a ≥1.25 Points/Month Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score at 28 Weeks Following the First Treatment as Compared to Placebo NO (%)	64 Participants	68 Participants

SECONDARY outcome

Timeframe: 28 weeks following the first intrathecal injection

Outcome measures

Outcome measures
Measure	NurOwn® (MSC-NTF Cells) n=95 Participants NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10'6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors Bone marrow aspiration	Placebo n=94 Participants One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection Bone marrow aspiration
Number of Participants Whose Disease Progression is Halted or Improved as Measured by a 100% or Greater Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score of NurOwn® Treatment vs. Placebo YES (%)	13 Participants	13 Participants
Number of Participants Whose Disease Progression is Halted or Improved as Measured by a 100% or Greater Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score of NurOwn® Treatment vs. Placebo NO (%)	82 Participants	81 Participants

SECONDARY outcome

Timeframe: 28 weeks following the first intrathecal injection

Outcome measures

Outcome measures
Measure	NurOwn® (MSC-NTF Cells) n=95 Participants NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10'6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors Bone marrow aspiration	Placebo n=94 Participants One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection Bone marrow aspiration
Score of NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by Change From Baseline in ALSFRS-R Score at Week 28	-5.52 score on a scale Standard Error 0.670	-5.88 score on a scale Standard Error 0.665

SECONDARY outcome

Timeframe: 28 weeks following the first intrathecal injection

The combined Assessment of Function and Survival (CAFS) is a composite endpoint based on (1) the change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) score and (2) time to death. On the ALSFRS-R, 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a total score range (minimum and maximum score) of 0-48 (sum of all 12 items). The higher the score the better functioning. For the survival endpoint, the longer time the better outcome. A patient's CAFS score represents a patient's rank in the study based on comparing the patient's outcome for both the change in ALSFRS-R and the time to death to all other patients in the study in a pairwise fashion. The ranked scores range from 001 to 189 (the number of subjects in the mITT population) with larger rank score numbers associated with a better outcome. The reported values are the mean rank scores in each group for the composite endpoint.

Outcome measures

Outcome measures
Measure	NurOwn® (MSC-NTF Cells) n=95 Participants NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10'6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors Bone marrow aspiration	Placebo n=94 Participants One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection Bone marrow aspiration
NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by the Combined Assessment of Function and Survival at 28 Weeks	73.74 score on a scale Standard Error 5.210	72.21 score on a scale Standard Error 4.890

Adverse Events

NurOwn® (MSC-NTF Cells)

Serious events: 23 serious events

Other events: 93 other events

Deaths: 10 deaths

Placebo

Serious events: 17 serious events

Other events: 92 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Brainstorm Cell Therapeutics

Phone: +1-201-488-0460

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	NurOwn® (MSC-NTF Cells) n=95 participants at risk NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10\^6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors Bone marrow aspiration	Placebo n=94 participants at risk One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection Bone marrow aspiration
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.3% 5/95 • Number of events 6 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	3.2% 3/94 • Number of events 3 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Respiratory, thoracic and mediastinal disorders Respiratory distress	2.1% 2/95 • Number of events 2 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Respiratory, thoracic and mediastinal disorders Respiratory muscle weakness	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Gastrointestinal disorders Dysphagia	3.2% 3/95 • Number of events 3 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	2.1% 2/94 • Number of events 2 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
General disorders Asthenia	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
General disorders Disease progression	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	2.1% 2/94 • Number of events 2 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
General disorders Euthanasia	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
General disorders Pain	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Infections and infestations Pneumonia	2.1% 2/95 • Number of events 2 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	2.1% 2/94 • Number of events 3 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Infections and infestations Intervertebral discitis	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Infections and infestations Clostridium difficile infection	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Infections and infestations Sepsis	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Fall	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Procedural complication	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Procedural pain	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Skull fracture	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Subdural haematoma	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Procedural headache	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Procedural nausea	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Nervous system disorders Dizziness	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Nervous system disorders Loss of consciousness	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Nervous system disorders Syncope	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Nervous system disorders Cerebral haemorrhage	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Nervous system disorders Cerebrospinal fluid leakage	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Cardiac disorders Palpitations	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Cardiac disorders Cardiac arrest	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Metabolism and nutrition disorders Malnutrition	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Metabolism and nutrition disorders Dehydration	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Renal and urinary disorders Urinary retention	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Renal and urinary disorders Renal colic	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Vascular disorders Haemorrhage	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	0.00% 0/94 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Vascular disorders Deep vein thrombosis	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Immune system disorders Anaphylactic reaction	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.

Other adverse events
Measure	NurOwn® (MSC-NTF Cells) n=95 participants at risk NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10\^6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors Bone marrow aspiration	Placebo n=94 participants at risk One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection Bone marrow aspiration
Injury, poisoning and procedural complications Procedural pain	52.6% 50/95 • Number of events 145 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	36.2% 34/94 • Number of events 52 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Procedural headache	32.6% 31/95 • Number of events 58 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	31.9% 30/94 • Number of events 51 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Fall	29.5% 28/95 • Number of events 61 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	36.2% 34/94 • Number of events 76 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Post lumbar puncture syndrome	23.2% 22/95 • Number of events 36 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	30.9% 29/94 • Number of events 48 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Post procedural complication	16.8% 16/95 • Number of events 22 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	7.4% 7/94 • Number of events 10 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Contusion	9.5% 9/95 • Number of events 9 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	9.6% 9/94 • Number of events 16 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Laceration	7.4% 7/95 • Number of events 7 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	11.7% 11/94 • Number of events 12 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Postoperative fever	7.4% 7/95 • Number of events 7 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 2 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Limb injury	6.3% 6/95 • Number of events 7 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 2 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Procedural anxiety	5.3% 5/95 • Number of events 7 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Injury, poisoning and procedural complications Skin abrasion	3.2% 3/95 • Number of events 3 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	5.3% 5/94 • Number of events 8 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Musculoskeletal and connective tissue disorders Back pain	44.2% 42/95 • Number of events 78 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	25.5% 24/94 • Number of events 33 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Musculoskeletal and connective tissue disorders Pain in extremity	16.8% 16/95 • Number of events 29 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	11.7% 11/94 • Number of events 15 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	15.8% 15/95 • Number of events 16 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	8.5% 8/94 • Number of events 9 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Musculoskeletal and connective tissue disorders Coccydynia	11.6% 11/95 • Number of events 14 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Musculoskeletal and connective tissue disorders Muscular weakness	11.6% 11/95 • Number of events 15 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	12.8% 12/94 • Number of events 16 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Musculoskeletal and connective tissue disorders Arthralgia	10.5% 10/95 • Number of events 11 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	7.4% 7/94 • Number of events 7 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Musculoskeletal and connective tissue disorders Muscle spasms	9.5% 9/95 • Number of events 14 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	6.4% 6/94 • Number of events 6 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Musculoskeletal and connective tissue disorders Muscle tightness	7.4% 7/95 • Number of events 7 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	1.1% 1/94 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Musculoskeletal and connective tissue disorders Myalgia	7.4% 7/95 • Number of events 8 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	2.1% 2/94 • Number of events 2 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Musculoskeletal and connective tissue disorders Neck pain	7.4% 7/95 • Number of events 9 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	8.5% 8/94 • Number of events 8 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	3.2% 3/95 • Number of events 4 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	5.3% 5/94 • Number of events 5 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Nervous system disorders Headache	47.4% 45/95 • Number of events 85 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	34.0% 32/94 • Number of events 57 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Nervous system disorders Dizziness	5.3% 5/95 • Number of events 6 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	5.3% 5/94 • Number of events 5 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Nervous system disorders Dysarthria	2.1% 2/95 • Number of events 3 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	5.3% 5/94 • Number of events 6 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Nervous system disorders Balance disorder	1.1% 1/95 • Number of events 1 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	5.3% 5/94 • Number of events 5 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Gastrointestinal disorders Nausea	16.8% 16/95 • Number of events 20 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	19.1% 18/94 • Number of events 22 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Gastrointestinal disorders Dysphagia	9.5% 9/95 • Number of events 9 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	5.3% 5/94 • Number of events 5 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Gastrointestinal disorders Constipation	7.4% 7/95 • Number of events 7 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	6.4% 6/94 • Number of events 6 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Gastrointestinal disorders Diarrhoea	5.3% 5/95 • Number of events 6 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	7.4% 7/94 • Number of events 9 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Gastrointestinal disorders Vomiting	3.2% 3/95 • Number of events 4 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	6.4% 6/94 • Number of events 6 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
General disorders Pyrexia	9.5% 9/95 • Number of events 10 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	9.6% 9/94 • Number of events 9 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
General disorders Injection site pain	8.4% 8/95 • Number of events 13 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	9.6% 9/94 • Number of events 10 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
General disorders Chills	2.1% 2/95 • Number of events 3 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	5.3% 5/94 • Number of events 5 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
General disorders Fatigue	0.00% 0/95 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	8.5% 8/94 • Number of events 8 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Infections and infestations Nasopharyngitis	8.4% 8/95 • Number of events 8 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	5.3% 5/94 • Number of events 6 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Infections and infestations Upper respiratory tract infection	6.3% 6/95 • Number of events 7 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	12.8% 12/94 • Number of events 12 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Respiratory, thoracic and mediastinal disorders Cough	4.2% 4/95 • Number of events 5 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	7.4% 7/94 • Number of events 7 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.2% 4/95 • Number of events 4 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	6.4% 6/94 • Number of events 8 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Psychiatric disorders Anxiety	5.3% 5/95 • Number of events 5 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	5.3% 5/94 • Number of events 5 • from the screening visit through the end of the study period (28 weeks after first treatment) AE means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.