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
Copolymer 1
20 mg subcutaneously once daily
n=125Placebo
Matching subcutaneous injection once daily
n=126Primary endpoint
Annualized relapse rate
2 years
Primary endpoint results
Annualized relapse rate
Relapses per participant-year
29% lower relapse rate with copolymer 1 (P=0.007).
Selected secondary outcomes
The distribution of patients who improved, remained unchanged, or worsened favored copolymer 1 (P=0.037).
15.2% with copolymer 1 and 13.5% with placebo.
Who was studied
Key inclusion criteria
- Age 18–45 years
- RRMS diagnosis: clinically definite or laboratory-supported definite MS (Poser criteria)
- Baseline EDSS 0–5.0; ambulatory
- At least 2 documented relapses in the previous 2 years; first relapse at least 1 year before entry
- Neurologically stable for at least 30 days
Key exclusion criteria
- Previous copolymer 1, cytotoxic treatment, or lymphoid irradiation
- Pregnancy or breastfeeding
- Insulin-dependent diabetes, HIV/HTLV-1 infection, or Lyme disease
- Required aspirin or chronic NSAID treatment
Participants at baseline
| Characteristic | Copolymer 1N=125 | PlaceboN=126 |
|---|---|---|
| Age, years — mean ± SD | 34.6 ± 6.0 | 34.3 ± 6.5 |
| Female sex — n (%) | 88 (70.4%) | 96 (76.2%) |
| MS duration, years — mean ± SD | 7.3 ± 4.9 | 6.6 ± 5.1 |
| EDSS — mean ± SD | 2.8 ± 1.2 | 2.4 ± 1.3 |
| Relapses in previous 2 years — mean ± SD | 2.9 ± 1.3 | 2.9 ± 1.1 |
| Ambulation index — mean ± SD | 1.2 ± 1.0 | 1.1 ± 0.9 |
SD: standard deviation; EDSS: Expanded Disability Status Scale.
Source: Johnson et al., Neurology 1995, Table 2
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.
Later safety context
Later FDA warning (2025): a boxed warning was added for rare, potentially fatal anaphylaxis with glatiramer acetate. Anaphylaxis is distinct from the transient post-injection reaction described in the controlled trial.
FDA, Glatiramer acetate safety communication, January 22, 2025 ↗Why it mattered
Copolymer 1 established a non-interferon approach to reducing relapses in RRMS. Its pivotal result broadened treatment options beyond the earliest interferon therapies, while the nonsignificant sustained-disability progression comparison limited conclusions for that endpoint.
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.