Amyotrophic Lateral Sclerosis
Conditions
Brief summary
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).
Interventions
DRUG40 mg glatiramer acetate
parenteral drug
DRUGPlacebo
Sponsors
Teva Pharmaceutical Industries, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of definite or probable ALS in accordance with the El-Escorial criteria. 2. Subject has experienced his/her first ALS symptoms within 3 years prior to the screening visit. 3. Slow VC test equal or greater than 70% of the predicted value. 4. The sum of the 3 respiratory items on the ALSFRS-R must total at least 10 points. 5. Stable dose of riluzole for at least 8 weeks prior to screening. 6. Age - 18-70 (inclusive).
Exclusion criteria
1. The use of invasive or non-invasive ventilation. 2. Subject having undergone gastrostomy. 3. Subject with any clinically significant or unstable medical condition. 4. Subjects participating in any other clinical trial (within 12 weeks prior to screening and thereafter). 5. Additional criteria per protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Slope of Change From Baseline in the ALS Functional Rating Scale (ALSFRS-R) | Baseline, Weeks 4, 8, 12, 17, 22, 26, 31, 36, 40, 44, 48, 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Event: Death, Tracheostomy, Permanent Assisted Ventilation | Baseline up to 52 weeks | 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. |
Countries
Belgium, France, Germany, Israel, Italy, United Kingdom
Participant flow
Pre-assignment details
366 participants were randomized in a 1:1 ratio to one of two treatment groups, Glatiramer Acetate 40 mg or matching placebo. The study duration was 52 weeks with a follow up period of up to 44 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Glatiramer Acetate 40mg Pre-filled syringe of 40 mg glatiramer acetate (GA) for injection, administered subcutaneously once a day | 184 |
| Placebo Pre-filled syringe of matching placebo, administered subcutaneously once a day | 182 |
| Total | 366 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 20 | 9 |
| Overall Study | Death | 18 | 16 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | prescheduled medical intervention | 0 | 1 |
| Overall Study | Withdrawal by Subject | 15 | 12 |
Baseline characteristics
| Characteristic | Placebo | Total | Glatiramer Acetate 40mg |
|---|---|---|---|
| Age, Continuous | 54.7 Years STANDARD_DEVIATION 9.6 | 55.2 Years STANDARD_DEVIATION 9.6 | 55.7 Years STANDARD_DEVIATION 9.6 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 182 Participants | 364 Participants | 182 Participants |
| Sex: Female, Male Female | 72 Participants | 141 Participants | 69 Participants |
| Sex: Female, Male Male | 110 Participants | 225 Participants | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 22 / 184 | 17 / 182 |
| other Total, other adverse events | 167 / 184 | 133 / 182 |
| serious Total, serious adverse events | 55 / 184 | 54 / 182 |
Outcome results
Primary
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.
Time frame: Baseline, Weeks 4, 8, 12, 17, 22, 26, 31, 36, 40, 44, 48, 52
Population: The intent-to-treat (ITT) analysis set consisted of all randomized participants who took at least one dose of the study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glatiramer Acetate 40mg | Slope of Change From Baseline in the ALS Functional Rating Scale (ALSFRS-R) | -1.05 Units on a Scale per Month | Standard Error 0.059 |
| Placebo | Slope of Change From Baseline in the ALS Functional Rating Scale (ALSFRS-R) | -1.00 Units on a Scale per Month | Standard Error 0.058 |
Comparison: Analysis compares the ALSFRS-R slopes of change from baseline between treatment groups. Analysis includes the following covariates: time from randomization, treatment group, time by treatment interaction, center, Riluzole use, age, site of ALS onset, time from ALS onset and baseline ALSFRS-R score.p-value: 0.480795% CI: [-0.22, 0.1]ANCOVA
Secondary
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.
Time frame: Baseline up to 52 weeks
Population: The intent-to-treat (ITT) analysis set consisted of all randomized participants who took at least one dose of the study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glatiramer Acetate 40mg | Time to Event: Death, Tracheostomy, Permanent Assisted Ventilation | NA Days |
| Placebo | Time to Event: Death, Tracheostomy, Permanent Assisted Ventilation | NA Days |
Comparison: Analysis covariates are center, riluzole use, site of ALS onset, time from ALS onset, baseline ALSFRS-R score, baseline slow vital capacity (VC) and baseline body mass index (BMI).p-value: 0.858395% CI: [0.56, 2.005]Regression, Cox