Trial Outcomes & Findings for Natalizumab High Titer Immunogenicity and Safety (NCT NCT00516893)
NCT ID: NCT00516893
Last Updated: 2014-05-15
Results Overview
Negative: no detectable antibody at all post-baseline visits. Persistent positive: antibody positive at 2 or more post-baseline visits at least 42 days apart, or positive at the last post-baseline visit. Transient positive: antibody positive at only 1 post-baseline visit prior to the last visit.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
113 participants
Primary outcome timeframe
Assessed every 12 weeks from Week 0 (Baseline) to Week 36
Results posted on
2014-05-15
Participant Flow
Participant milestones
| Measure |
Natalizumab High Titer
natalizumab high titer 300 mg administered as intravenous (IV) infusion over 60 minutes once every 4 weeks for up to 9 doses
|
|---|---|
|
Overall Study
STARTED
|
113
|
|
Overall Study
Received Study Treatment
|
112
|
|
Overall Study
COMPLETED
|
92
|
|
Overall Study
NOT COMPLETED
|
21
|
Reasons for withdrawal
| Measure |
Natalizumab High Titer
natalizumab high titer 300 mg administered as intravenous (IV) infusion over 60 minutes once every 4 weeks for up to 9 doses
|
|---|---|
|
Overall Study
Lost to Follow-up
|
4
|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Noncompliance
|
2
|
|
Overall Study
Death
|
1
|
|
Overall Study
Persistent Antibodies per Protocol
|
6
|
|
Overall Study
Relocated
|
1
|
|
Overall Study
Pregnancy
|
1
|
|
Overall Study
Received Medication From Another Study
|
1
|
Baseline Characteristics
Natalizumab High Titer Immunogenicity and Safety
Baseline characteristics by cohort
| Measure |
Natalizumab High Titer
n=113 Participants
natalizumab high titer 300 mg administered as intravenous (IV) infusion over 60 minutes once every 4 weeks for up to 9 doses
|
|---|---|
|
Age, Continuous
|
38.9 years
STANDARD_DEVIATION 8.64 • n=99 Participants
|
|
Age, Customized
≥ 18 to < 20 years
|
2 participants
n=99 Participants
|
|
Age, Customized
≥ 20 to < 30 years
|
15 participants
n=99 Participants
|
|
Age, Customized
≥ 30 to < 40 years
|
43 participants
n=99 Participants
|
|
Age, Customized
≥ 40 to < 50 years
|
41 participants
n=99 Participants
|
|
Age, Customized
≥ 50 to < 56 years
|
10 participants
n=99 Participants
|
|
Age, Customized
≥ 56 years
|
2 participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
91 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black
|
8 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
91 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
12 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=99 Participants
|
|
Region of Enrollment
United States
|
113 participants
n=99 Participants
|
|
Expanded Disability Status Score (EDSS) Score
|
3.66 scores on a scale
STANDARD_DEVIATION 1.817 • n=99 Participants
|
PRIMARY outcome
Timeframe: Assessed every 12 weeks from Week 0 (Baseline) to Week 36Population: Participants who received at least 1 dose of natalizumab, had a negative baseline antibody result, and had at least 1 antibody assessment after the first dose.
Negative: no detectable antibody at all post-baseline visits. Persistent positive: antibody positive at 2 or more post-baseline visits at least 42 days apart, or positive at the last post-baseline visit. Transient positive: antibody positive at only 1 post-baseline visit prior to the last visit.
Outcome measures
| Measure |
Natalizumab High Titer
n=108 Participants
natalizumab high titer 300 mg administered as intravenous (IV) infusion over 60 minutes once every 4 weeks for up to 9 doses
|
|---|---|
|
Number of Participants With Anti-Natalizumab Antibody Negative, Transient Positive, and Persistent Positive Status
Transient positive
|
3 participants
|
|
Number of Participants With Anti-Natalizumab Antibody Negative, Transient Positive, and Persistent Positive Status
Antibody negative
|
96 participants
|
|
Number of Participants With Anti-Natalizumab Antibody Negative, Transient Positive, and Persistent Positive Status
Persistent positive
|
9 participants
|
SECONDARY outcome
Timeframe: AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.Population: Participants who received at least 1 dose of study drug.
AE: any sign, symptom, or diagnosis/disease that was unfavorable or unintended, new, or if pre-existing, worsened in a participant administered a study treatment and that did not necessarily have a causal relationship with this treatment. SAE: an event that resulted in death; an event that, in the view of the investigator, placed the participant at immediate risk of death (life-threatening event); an outcome that resulted in a congenital anomaly/birth defect diagnosed in a child of a participant in this study; an event that required or prolonged inpatient hospitalization; an event that resulted in persistent or significant disability/incapacity; any other medically important event that, in the opinion of the investigator, may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed above. Events were classified as 'related' or 'not related' to study drug, and categorized as 'mild' moderate' or 'severe' per protocol.
Outcome measures
| Measure |
Natalizumab High Titer
n=112 Participants
natalizumab high titer 300 mg administered as intravenous (IV) infusion over 60 minutes once every 4 weeks for up to 9 doses
|
|---|---|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
Adverse event (AE)
|
106 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
Moderate or severe AE
|
63 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
Severe AE
|
18 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
AE related to study drug
|
23 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
Serious adverse event (SAE)
|
7 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
SAE related to study drug
|
0 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
Treatment discontinuation due to AE
|
4 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
Withdrawal from study due to AE
|
3 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Participants with EDSS scores at Baseline and Week 36 (includes participants who withdrew from the study).
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. The change in EDSS at Month 36 was calculated as EDSS at Month 36 minus EDSS at baseline.
Outcome measures
| Measure |
Natalizumab High Titer
n=106 Participants
natalizumab high titer 300 mg administered as intravenous (IV) infusion over 60 minutes once every 4 weeks for up to 9 doses
|
|---|---|
|
Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 36
|
-0.19 scores on a scale
Standard Deviation 0.982
|
SECONDARY outcome
Timeframe: Through Week 36Population: Participants who received at least 1 dose of study drug.
Annualized relapse rate was calculated as the total number of relapses that occurred during the study divided by the total number of years the participant was followed in the study. The annualized relapse rate was based only on those relapses that were determined to meet the definition of relapse per the investigator's clinical judgment. New or recurrent symptoms that occurred less than 30 days following the onset of a protocol-defined relapse were considered part of the same relapse.
Outcome measures
| Measure |
Natalizumab High Titer
n=112 Participants
natalizumab high titer 300 mg administered as intravenous (IV) infusion over 60 minutes once every 4 weeks for up to 9 doses
|
|---|---|
|
Annualized Relapse Rate
|
0.13 relapses/participant-years
|
Adverse Events
Natalizumab High Titer
Serious events: 7 serious events
Other events: 79 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Natalizumab High Titer
n=112 participants at risk
natalizumab high titer 300 mg administered as intravenous (IV) infusion over 60 minutes once every 4 weeks for up to 9 doses
|
|---|---|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
1.8%
2/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
1.8%
2/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Multiple sclerosis relapse
|
1.8%
2/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.89%
1/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Vascular disorders
Chest pain
|
0.89%
1/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.89%
1/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Demyelination
|
0.89%
1/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Gastroenteritis
|
0.89%
1/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Natalizumab High Titer
n=112 participants at risk
natalizumab high titer 300 mg administered as intravenous (IV) infusion over 60 minutes once every 4 weeks for up to 9 doses
|
|---|---|
|
Nervous system disorders
Headache
|
19.6%
22/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
General disorders
Fatigue
|
17.9%
20/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
17.9%
20/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Urinary tract infection
|
10.7%
12/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Sinusitis
|
9.8%
11/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.9%
10/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Fall
|
8.9%
10/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Multiple sclerosis relapse
|
7.1%
8/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Hypoaesthesia
|
8.0%
9/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
8.0%
9/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.2%
7/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Contusion
|
6.2%
7/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Eye disorders
Visual acuity reduced
|
6.2%
7/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
General disorders
Gait disturbance
|
5.4%
6/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.4%
6/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
5.4%
6/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
|
Eye disorders
Vision blurred
|
5.4%
6/112 • AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Includes all participants who received at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
- Publication restrictions are in place
Restriction type: OTHER