Trial Outcomes & Findings for Phase 2, Randomized, Double Blind, Placebo Controlled Multicenter Study of Autologous MSC-NTF Cells in Patients With ALS (NCT NCT02017912)

NCT ID: NCT02017912

Last Updated: 2024-06-06

Results Overview

Safety assessed based on the incidence of treatment-emergent adverse events (TEAEs) (including serious adverse events \[SAEs\]) including clinically relevant changes in vital signs, clinical laboratory assessments, physical and neurological examinations, and electrocardiogram (ECG) tests, during transplantation of expanded autologous MSC-NTF cells administered on a single occasion via combined intrathecal (IT) administration and intramuscular (IM) injections

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

48 participants

Primary outcome timeframe

Up to 24 weeks following the first intrathecal injection, or End of Study

Results posted on

2024-06-06

Participant Flow

The subject population was planned to include up to 48 treated adults, aged 18 to 75 years, with ALS who were randomly assigned (3:1) to the treatment group (36 patients) or placebo group (12 patients). 48 patients were randomized and all 48 patients underwent treatment.

Visit 1 was the Screening Visit. Visit 2 was the enrollment visit and the pre-transplantation follow-up period (Week 4-6). Visit 3 was the second visit of the pre-transplantation follow-up period (Week 8-10), and 1 week before BMA. Visit 3, patients were randomized into two arms at a 3:1 ratio. Any patient discontinuing the study prior to transplantation of cells (or placebo) injections was replaced with another subject to meet the target of 48 transplanted patients.

Participant milestones

Participant milestones
Measure	Nurown MSC-NTF Cells Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration Nurown MSC-NTF cells: Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration	Excipient Combined intramuscular and intrathecal placebo administration Placebo: Excipient administration by combined intramuscular and intrathecal administration
Overall Study STARTED	36	12
Overall Study COMPLETED	33	10
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Nurown MSC-NTF Cells Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration Nurown MSC-NTF cells: Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration	Excipient Combined intramuscular and intrathecal placebo administration Placebo: Excipient administration by combined intramuscular and intrathecal administration
Overall Study Withdrawal by Subject	2	1
Overall Study miscellaneous	1	1

Baseline Characteristics

Phase 2, Randomized, Double Blind, Placebo Controlled Multicenter Study of Autologous MSC-NTF Cells in Patients With ALS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nurown MSC-NTF Cells n=36 Participants Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration Nurown MSC-NTF cells: Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration	Excipient n=12 Participants Combined intramuscular and intrathecal placebo administration Placebo: Excipient administration by combined intramuscular and intrathecal administration	Total n=48 Participants Total of all reporting groups
Age, Continuous	50.3 years STANDARD_DEVIATION 11.90 • n=5 Participants	53.5 years STANDARD_DEVIATION 9.11 • n=7 Participants	51.1 years STANDARD_DEVIATION 11.27 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	2 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	10 Participants n=7 Participants	35 Participants n=5 Participants
Region of Enrollment United States	36 participants n=5 Participants	12 participants n=7 Participants	48 participants n=5 Participants
El Escorial Criteria Possible	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
El Escorial Criteria Laboratory-supported Probable	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
El Escorial Criteria Probable	16 Participants n=5 Participants	7 Participants n=7 Participants	23 Participants n=5 Participants
El Escorial Criteria Definite	12 Participants n=5 Participants	3 Participants n=7 Participants	15 Participants n=5 Participants
ALS Medical History since diagnosis	9.00 months STANDARD_DEVIATION 5.578 • n=5 Participants	9.01 months STANDARD_DEVIATION 4.637 • n=7 Participants	9.00 months STANDARD_DEVIATION 5.311 • n=5 Participants
ALS Medical History since first symptom	17.62 months STANDARD_DEVIATION 3.796 • n=5 Participants	16.75 months STANDARD_DEVIATION 3.104 • n=7 Participants	17.40 months STANDARD_DEVIATION 3.624 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 weeks following the first intrathecal injection, or End of Study

Population: The safety population includes all randomized participants who receive any study treatment (MSC-NTF or placebo) including those who do not complete the study. The safety population was analyzed based upon the treatment received.

Outcome measures

Outcome measures
Measure	Nurown MSC-NTF Cells n=36 Participants Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration Nurown MSC-NTF cells: Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration	Excipient n=12 Participants Combined intramuscular and intrathecal placebo administration Placebo: Excipient administration by combined intramuscular and intrathecal administration
Number of Patients With at Least One Treatment Emergent Adverse Events	36 Participants	12 Participants

SECONDARY outcome

Timeframe: Up to 24 weeks following the first intrathecal injection

Population: The Full Analysis Set (FAS) includes all participants who were randomized. The FAS was analyzed based upon treatment group subjects were randomized to.

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. The total score of ALSFRS-R ranges from 0-48, with higher score being better. The slope of ALSFRS-R for the pre- and post-treatment is obtained from a linear regression model using all available data points in the corresponding period, respectively. The change in slope is obtained from a fixed-effect linear model which is defined as the post-treatment slope minus the pre-treatment slope. The unit of the slope is score on a scale per month. A positive change in slope, means that the patient's decline in the ALSFRS-R score is slower than pre-treatment. A negative change in slope, means that the patient decline in the ALSFRS-R score is faster than pre-treatment.

Outcome measures

Outcome measures
Measure	Nurown MSC-NTF Cells n=36 Participants Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration Nurown MSC-NTF cells: Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration	Excipient n=12 Participants Combined intramuscular and intrathecal placebo administration Placebo: Excipient administration by combined intramuscular and intrathecal administration
Change in Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) Slopes From the Pre-transplantation Period to the Post-transplantation Period Between the Treatment and Placebo Groups Through 24 Weeks Post-transplantation.	-0.556 score on a scale per month Standard Error 0.2784	-0.356 score on a scale per month Standard Error 0.4821

SECONDARY outcome

Timeframe: Up to 24 weeks following the first intrathecal injection

Population: The Full Analysis Set (FAS) includes all randomized participants who were randomized. The FAS will be analyzed based upon treatment group subjects were randomized to.

SVC measures the maximum amount of air exhaled in a single breath, this lung function is influenced by gender, height, and age, in a complex, non-linear, way. The SVC reported is a normalized value obtained from a non-linear prediction model that accounts for the influence of participant's gender, height and age. SVC was done 3 times at each visit, in order to capture and report the maximal, effort-dependent, lung function that a participant can deliver. The slope of SVC is obtained from a linear regression model using all available data points in the corresponding period, respectively. The change in slope is from a fixed-effect linear model which is defined as the post-treatment slope minus the pre-treatment slope. The unit of the slope is score on a scale per month. Positive change in slope, means that the patient's decline in the SVC score is slower than pre-treatment. Negative change in slope, means that the patient decline in the SVC score is faster than pre-treatment.

Outcome measures

Outcome measures
Measure	Nurown MSC-NTF Cells n=36 Participants Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration Nurown MSC-NTF cells: Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration	Excipient n=11 Participants Combined intramuscular and intrathecal placebo administration Placebo: Excipient administration by combined intramuscular and intrathecal administration
Change in SVC Slopes From the Pre-transplantation Period to the Post-transplantation Period Between the Treatment and Placebo Groups Through 24 Weeks Post-transplantation	-0.73 score on a scale per month. Standard Error 0.430	-0.31 score on a scale per month. Standard Error 0.769

Adverse Events

Nurown MSC-NTF Cells

Serious events: 8 serious events

Other events: 36 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Nurown MSC-NTF Cells n=36 participants at risk Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration Nurown MSC-NTF cells: Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration	Placebo n=12 participants at risk Combined intramuscular and intrathecal placebo administration Placebo: Excipient administration by combined intramuscular and intrathecal administration
Gastrointestinal disorders Dysphagia	16.7% 6/36 • Number of events 6 • From the screening visit through the end of the study period (24 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.	8.3% 1/12 • Number of events 1 • From the screening visit through the end of the study period (24 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	5.6% 2/36 • Number of events 2 • From the screening visit through the end of the study period (24 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% 0/12 • From the screening visit through the end of the study period (24 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	2.8% 1/36 • Number of events 1 • From the screening visit through the end of the study period (24 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% 0/12 • From the screening visit through the end of the study period (24 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 fatigue	2.8% 1/36 • Number of events 1 • From the screening visit through the end of the study period (24 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% 0/12 • From the screening visit through the end of the study period (24 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 Stoma site pain	2.8% 1/36 • Number of events 1 • From the screening visit through the end of the study period (24 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% 0/12 • From the screening visit through the end of the study period (24 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 Hypophagia	2.8% 1/36 • Number of events 1 • From the screening visit through the end of the study period (24 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% 0/12 • From the screening visit through the end of the study period (24 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.
Reproductive system and breast disorders Breast hyperplasia	9.1% 1/11 • Number of events 1 • From the screening visit through the end of the study period (24 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% 0/2 • From the screening visit through the end of the study period (24 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

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