REGAIN
Clinical Question
To assess the safety and efficacy of eculizumab, a terminal complement inhibitor, in patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis
Bottom Line
Eculizumab (anti-C5 complement inhibitor) did not meet primary endpoint in refractory generalized AChR-positive MG: MG-ADL responder rate 55.7% vs 41.2% placebo (P=0.0698 worst-rank ANCOVA). However, sensitivity analyses and secondary endpoints showed significant improvement. 125 patients, 26 weeks. Published Lancet Neurology 2017. Led to FDA approval via totality of evidence.
Major Points
- Primary endpoint missed: MG-ADL change by worst-rank ANCOVA P=0.0698 (NS). Predefined sensitivity analysis P=0.0058.
- MG-ADL responder rate: 55.7% vs 41.2% (descriptive). QMG responder rate: 45.9% vs 30.2%.
- All secondary endpoints favored eculizumab: QMG, MG-QoL15, MGC — significant by prespecified sensitivity analyses.
- 125 patients with refractory generalized AChR-Ab+ MG (failed ≥2 ISTs or 1 IST + IVIG/PLEX dependent).
- Eculizumab 900mg IV weekly ×4, then 1200mg every 2 weeks. 26-week randomized, then open-label extension.
- Complement C5 inhibition: blocks MAC formation. Meningococcal vaccination required.
- AEs: headache (24%), nasopharyngitis (18%), nausea (13%). 1 meningococcal infection (treated successfully).
- Published Lancet Neurology 2017 (Howard et al.). Alexion sponsored.
- FDA approved eculizumab for generalized MG 2017 based on totality of evidence despite missed primary.
- Landmark: first complement inhibitor approved for MG. Opened complement pathway as MG therapeutic target.
Design
Study Type: Phase 3, randomized, double-blind, placebo-controlled trial
Randomization:
Blinding: Double-blind
Follow-up Duration: 26 weeks
Centers: 0
Countries:
Sample Size: 125
Inclusion Criteria
- Age ≥18 years
- AChR antibody-positive generalized MG
- MG-ADL score ≥6
- MGFA class II-IV
- vaccinated against N. meningitidis
- failed ≥2 immunosuppressive therapies or ≥1 IST plus chronic IVIg/PLEX for 12 months without symptom control
Arms
| Field | Eculizumab | Control |
|---|---|---|
| Intervention | Eculizumab | Placebo (1:1) |
| Duration |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| • Primary: MG-ADL worst-rank ANCOVA: LS mean rank 56.6 vs 68.3, difference -11.7 (95% CI -24.3 to 0.96), p=0.0698 • QMG worst-rank ANCOVA: difference -16.0, p=0.0129 • MG-ADL responders (≥3-point improvement): 60% eculizumab vs 40% placebo | Primary | p=0.0698 | |||
| Not reported | Adverse | No adverse event data extracted for this trial |
Based on: REGAIN (2017)
Content summarized and formatted by NeuroTrials.ai.