Trial Outcomes & Findings for Ph1 T-Regulatory Cells in Amyotrophic Lateral Sclerosis (NCT NCT03241784)

Results Overview

Adverse events and serious adverse events related to Treg infusions were monitored throughout the study.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

3 participants

Primary outcome timeframe

Adverse events related to Treg infusions at Baseline to up to two years or study participation, whichever is occurs first.

Results posted on

2026-06-17

Participant Flow

Enrollment began 2/2016 and ended 9/1/2016, with the clinic identifying patients with a sporadic or familial amyotrophic lateral sclerosis (ALS) diagnosis.

Participant milestones

Participant milestones
Measure	Treatment Arm All subjects with ALS enrolled to one arm and received IV infusions of their autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg \& subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times per week.
Overall Study STARTED	3
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Arm All subjects with ALS enrolled to one arm and received IV infusions of their autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg \& subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times per week.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Ph1 T-Regulatory Cells in Amyotrophic Lateral Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Arm n=3 Participants All subjects are enrolled to an open study arm consisting of autologous T-regulatory lymphocytes IV infusions at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week.
Age, Categorical <=18 years	0 Participants n=9 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=9 Participants
Age, Categorical >=65 years	0 Participants n=9 Participants
Age, Continuous	50 Years STANDARD_DEVIATION 5.3 • n=9 Participants
Sex: Female, Male Female	1 Participants n=9 Participants
Sex: Female, Male Male	2 Participants n=9 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=9 Participants
Race (NIH/OMB) Asian	0 Participants n=9 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants
Race (NIH/OMB) Black or African American	0 Participants n=9 Participants
Race (NIH/OMB) White	3 Participants n=9 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants
Region of Enrollment United States	3 participants n=9 Participants

PRIMARY outcome

Timeframe: Adverse events related to Treg infusions at Baseline to up to two years or study participation, whichever is occurs first.

Adverse events and serious adverse events related to Treg infusions were monitored throughout the study.

Outcome measures

Outcome measures
Measure	Treatment Arm n=3 Participants All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week. Autologous T-regulatory lymphocytes: intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg. Interleukin-2: Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
Number of Participants With Treatment-related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0) & Medical Dictionary for Regulatory Activities (MedDRA).	0 Participants

SECONDARY outcome

Timeframe: Baseline and at week 15

The AALS is a published, validated instrument based on objective testing in five categories (bulbar, respiratory function, arm and leg function, and muscle strength) with scores ranging from 30 (normal) to 164 (maximally impaired).

Outcome measures

Outcome measures
Measure	Treatment Arm n=3 Participants All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week. Autologous T-regulatory lymphocytes: intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg. Interleukin-2: Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
Appel ALS (AALS) Scale/Grading Baseline Appel ALS Grading	50 units on a scale Standard Deviation 7.87
Appel ALS (AALS) Scale/Grading Week 15 Appel ALS Grading	68 units on a scale Standard Deviation 12.36
Appel ALS (AALS) Scale/Grading Change from Baseline to Week 15	10.4 units on a scale Standard Deviation 6.84

SECONDARY outcome

Timeframe: Baseline to week 15

The ALSFRS-R (ALS Functional Rating Scale-Revised) is an orally administered validated instrument using an ordinal rating scale used to determine the a person's assessment of their capability and independence in 12 functional activities based on 10 questions related to motor, bulbar and respiratory function. Participants are asked to rate his/her impression of function regarding writing, self care, climbing stairs, and breathing. Each task is rated on a five-point scale from 0 = can't do to 4 = normal ability resulting in an overall score of 0 (worst) to 48 (best).

Outcome measures

Outcome measures
Measure	Treatment Arm n=3 Participants All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week. Autologous T-regulatory lymphocytes: intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg. Interleukin-2: Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) Baseline ALS FRS-r	40.3 score on a scale Standard Deviation 3.3
ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) Week 15 ALS FRS-r	38 score on a scale Standard Deviation 4.2
ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) Change between Baselines & Week 15 ALS FRS-r	2.33 score on a scale Standard Deviation 1.7

SECONDARY outcome

Timeframe: Mean and standard deviation represent the average of baseline and 3-month assessments.

Population: Treg percentage (CD4+CD25+FOXP3+ cells) within the total CD4+ population will be assessed by multicolor flow cytometry resulting in a percent value.

Treg percentage (CD4+CD25+FOXP3+ cells) within the total CD4+ population will be assessed by multicolor flow cytometry. Cluster of differentiation 4 (CD4 ) cells are also known as T cells, the white blood cells, which fight infection and play an important role in the immune system.

Outcome measures

Outcome measures
Measure	Treatment Arm n=3 Participants All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week. Autologous T-regulatory lymphocytes: intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg. Interleukin-2: Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
T-Regulatory Cells	2.9 percentage of Tregs Standard Deviation 0.19

SECONDARY outcome

Timeframe: Baseline to 3 months post treatment for a total of two years from baseline

Treg suppressive function of T-effector (Teff) cells will be assessed by \[3H\]-thymidine incorporation. 3H-thymidine is a radioactive nucleoside that is incorporated into a commonly used assay to measure lymphocyte proliferation. Correlation between changes in the rate of disease progression and the Treg percentage and function will be determined by Spearman's correlation analysis.

Outcome measures

Outcome measures
Measure	Treatment Arm n=3 Participants All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week. Autologous T-regulatory lymphocytes: intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg. Interleukin-2: Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
Treg Suppression Baseline %Treg suppressive function of Teffectors	37.1 percentage of cells Standard Deviation 17.2
Treg Suppression Month 3 %Treg suppressive function of Teffectors	49 percentage of cells Standard Deviation 16.5

SECONDARY outcome

Timeframe: Baseline to 3 months post-treatment for a total of two years from baseline

The percentage of Tregs, Th1 lymphocytes, assessed by multicolor flow cytometry.

Outcome measures

Outcome measures
Measure	Treatment Arm n=3 Participants All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week. Autologous T-regulatory lymphocytes: intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg. Interleukin-2: Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
T Helper Cells Type 1 (Th1) Lymphocytes Baseline % of Th1 lymphocytes	85.1 percentage of cells Standard Deviation 3.4
T Helper Cells Type 1 (Th1) Lymphocytes Month 3 % of Th1 lymphocytes	81.3 percentage of cells Standard Deviation 0.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Mean and standard deviation of the values from baseline and 3 months.

FVC (Forced Vital Capacity). Reduction of pulmonary function is the primary source of morbidity and mortality in ALS. FVC testing will be used to monitor respiratory function. FVC measures the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. The intent is to report the percent of predicted FVC value.

Outcome measures

Outcome measures
Measure	Treatment Arm n=3 Participants All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week. Autologous T-regulatory lymphocytes: intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg. Interleukin-2: Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
Pulmonary FVC - Exploratory Measure - Percent of Predicted FVC Baseline FVC	75 percentage of predicted FVC Standard Deviation 14.8
Pulmonary FVC - Exploratory Measure - Percent of Predicted FVC Month 3 FVC	75.7 percentage of predicted FVC Standard Deviation 25.1
Pulmonary FVC - Exploratory Measure - Percent of Predicted FVC Change from Baseline to Month 3 FVC	9.33 percentage of predicted FVC Standard Deviation 4.49

OTHER_PRE_SPECIFIED outcome

Timeframe: At Baseline and at 3 months intervals, up to two years from baseline (or as long as participant is involved in the study).

MIP (Maximum Inspiratory Pressure) measures the strength of muscles used during inspiration and assessed due to decreased pulmonary function resulting in a primary source of ALS morbidity and mortality. MIP is the lowest pressure developed during a forceful inspiration against an occluded airway, measured with a device during maximal inspiration from 0 (worst) to 100 (best) and recorded as a number with the units, cm H2O (centimeters of water). Declining MIP indicates worsening of pulmonary function and maintenance of MIP over time indicates the goal of sufficient/stable respiratory strength.

Outcome measures

Outcome measures
Measure	Treatment Arm n=3 Participants All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week. Autologous T-regulatory lymphocytes: intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg. Interleukin-2: Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
Pulmonary MIP - Exploratory Measure Baseline MIP	90 cm H2O Standard Deviation 29.4
Pulmonary MIP - Exploratory Measure Post-3months from Baseline MIP	85 cm H2O Standard Deviation 36.3
Pulmonary MIP - Exploratory Measure Change from Baseline to 3Months	5 cm H2O Standard Deviation 7.07

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 3 months post-treatment

Number of patients requiring a tracheostomy. Patients undergoing an elective, prophylactic or required tracheostomy is performed when a patient may not maintain adequate ventilation with non-invasive ventilation \[such as bilevel positive airway pressure (BIPAP) or average volume-assured pressure support (AVAPS)\], or could not produce adequate cough with a cough assist device to manage their secretions.

Outcome measures

Outcome measures
Measure	Treatment Arm n=3 Participants All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week. Autologous T-regulatory lymphocytes: intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg. Interleukin-2: Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
Need for Tracheostomy- Exploratory Measure Baseline Tracheostomy	0 participants
Need for Tracheostomy- Exploratory Measure Tracheostomy placed after Treg infusions	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 3 months post-treatment for a total of two years from baseline

Population: ALS patients

FVC (Forced Vital Capacity). Reduction of pulmonary function is the primary source of morbidity and mortality in ALS. FVC testing will be used to monitor respiratory function. FVC measures the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible; values less than 75% are indicative of the need for intervention and/or monitoring and optimal FVC values are greater than 76%.

Outcome measures

Outcome measures
Measure	Treatment Arm n=3 Participants All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week. Autologous T-regulatory lymphocytes: intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg. Interleukin-2: Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
Pulmonary FVC - Exploratory Measure	75.35 percentage of predicted FVC value Standard Deviation 7.3

Adverse Events

Treatment Arm

Serious events: 0 serious events

Other events: 1 other events

Deaths: 3 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment Arm n=3 participants at risk All subjects with ALS enrolled to one arm and received IV infusions of their autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg \& subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times per week.
Gastrointestinal disorders gastroenteritis	33.3% 1/3 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline. AEs and SAEs does not differ from ClinicalTrials.gov definition.
Infections and infestations Suspected upper respiratory infection	33.3% 1/3 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline. AEs and SAEs does not differ from ClinicalTrials.gov definition.
Injury, poisoning and procedural complications Facial ecchymosis post fall	33.3% 1/3 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline. AEs and SAEs does not differ from ClinicalTrials.gov definition.
Musculoskeletal and connective tissue disorders Mandible Fracture	33.3% 1/3 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline. AEs and SAEs does not differ from ClinicalTrials.gov definition.
Infections and infestations Pharyngitis	33.3% 1/3 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline. AEs and SAEs does not differ from ClinicalTrials.gov definition.
Musculoskeletal and connective tissue disorders Nocturnal Muscle Cramping	33.3% 1/3 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline. AEs and SAEs does not differ from ClinicalTrials.gov definition.
Infections and infestations Urinary Tract Infection	33.3% 1/3 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline. AEs and SAEs does not differ from ClinicalTrials.gov definition.
Gastrointestinal disorders Dysphagia worsened during study	33.3% 1/3 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline. AEs and SAEs does not differ from ClinicalTrials.gov definition.
Renal and urinary disorders urinary retention following PEG placement	33.3% 1/3 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline. AEs and SAEs does not differ from ClinicalTrials.gov definition.
Respiratory, thoracic and mediastinal disorders aspiration pneumonia related to worsening bulbar ALS	33.3% 1/3 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline. AEs and SAEs does not differ from ClinicalTrials.gov definition.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline. AEs and SAEs does not differ from ClinicalTrials.gov definition.

Additional Information

Stanley Appel, MD, Principal Investigator and Director of ALS Clinic

Houston Methodist Neurological Institute

Phone: 713-441-3760

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place