Copolymer 1 pivotal trial
Glatiramer acetate
This trial showed that daily subcutaneous copolymer 1—later named glatiramer acetate—reduced relapses in relapsing-remitting multiple sclerosis.
- Phase
- Phase III
- Population
- Relapsing-remitting multiple sclerosis (RRMS)
- Controlled period
- Oct 23, 1991 — May 25, 1994
What was compared
Intervention
Copolymer 1
20 mg subcutaneously once daily
n=125Comparator
Placebo
Matching subcutaneous injection once daily
n=126251 randomized2 years controlled phase
Primary endpoint
Prespecified outcome
Annualized relapse rate
2 years
Outcome figure
Primary endpoint results
Intervention Comparator or reference
Annualized relapse rate
Relapses per participant-year
29% lower relapse rate with copolymer 1 (P=0.007).
Selected secondary outcomes
EDSS change
The distribution of patients who improved, remained unchanged, or worsened favored copolymer 1 (P=0.037).
Withdrawals
15.2% with copolymer 1 and 13.5% with placebo.
Study population
- Randomized
- 251 randomized
- Age
- 18–45 years eligible
- Disability
- EDSS 0–5.0
- Disease definition
- Relapsing-remitting multiple sclerosis
Who entered the trial
Key inclusion criteria
- Definite relapsing-remitting multiple sclerosis
- At least two relapses during the previous 2 years
- Ambulatory disability range, EDSS 0–5.0
Key exclusion criteria
- Progressive disease without a relapsing course
- Recent immunosuppressive treatment
- Clinically important comorbidity that could confound evaluation
Safety signal
- Injection-site reaction was the most common adverse experience.
- A transient self-limited post-injection systemic reaction occurred in 15.2% with copolymer 1 and 3.2% with placebo.
Why it mattered
The study established a non-interferon immunomodulatory option and introduced one of the longest-used platform therapies in relapsing MS.
Important limitation
The modest sample and 2-year follow-up were suited to relapse detection but not uncommon safety events or long-term disability effects.