Clinical Trial of Glatiramer Acetate in Amyotrophic Lateral Sclerosis (ALS)

Study Overview
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Brief Summary
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Teva is developing 40 mg/ml Glatiramer Acetate (GA) Injection , administered once daily under the skin, for the treatment of ALS. The study drug is a higher dose formulation of Copaxone® (20 mg/ml GA), a marketed medication, approved for the treatment of relapsing-remitting multiple sclerosis. GA is an immunomodulating drug that has anti inflammatory and neuroprotective properties, which are believed to be of therapeutic value in ALS. The study treatment duration is 1 year (52 weeks).

Official Title
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A Multinational, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Tolerability and Safety of 40 mg Glatiramer Acetate Injection in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: 40 mg glatiramer acetate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of definite or probable ALS in accordance with the El-Escorial criteria. Subject has experienced his/her first ALS symptoms within 3 years prior to the screening visit. Slow VC test equal or greater than 70% of the predicted value. The sum of the 3 respiratory items on the ALSFRS-R must total at least 10 points. Stable dose of riluzole for at least 8 weeks prior to screening. Age - 18-70 (inclusive). Exclusion Criteria: The use of invasive or non-invasive ventilation. Subject having undergone gastrostomy. Subject with any clinically significant or unstable medical condition. Subjects participating in any other clinical trial (within 12 weeks prior to screening and thereafter). Additional criteria per protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 40 mg glatiramer acetate (GA)<br>Pre-filled syringe of 40 mg glatiramer acetate (GA) for injection, administered subcutaneously once a day. | Drug: 40 mg glatiramer acetate<br>* parenteral drug<br>|
| Placebo Comparator: Placebo<br>Pre-filled syringe of matching placebo, administered subcutaneously once a day. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Slope of Change From Baseline in the ALS Functional Rating Scale (ALSFRS-R) | The ALSFRS-R is a questionnaire-based scale for monitoring the progression of disability in patients with ALS. It is composed of 12 items, each scored between 0 and 4.The total score, calculated as the sum of these 12 items, ranges from 0 to 48. The higher the score, the less disabled the participant. Timepoints after baseline were included in calculation of slope of change in ALSFRS-R. Slope is derived from the time by treatment interaction term from the Repeated Measures Analysis of Covariance model. Descriptive statistics of the slope are reported. | Baseline, Weeks 4, 8, 12, 17, 22, 26, 31, 36, 40, 44, 48, 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Event: Death, Tracheostomy, Permanent Assisted Ventilation | Composite endpoint of time to death, tracheostomy, or permanent assisted ventilation analyzed using the Cox's proportional hazards model to compare the risk of death, tracheostomy, or permanent assisted ventilation between treatment groups. The model includes center country, Riluzole© use, site of ALS onset, time from ALS onset, and baseline ALSFRS-R score, baseline slow VC and baseline BMI as covariates. Because less than 50% of participants experienced the event, the median time to event (i.e. the descriptive statistic for the day for which 50% of participants experienced the event) could not be calculated. Hence the days are reported as not available. | Baseline up to 52 weeks |