PDF: CHAMPION-NMOSD
(2023)Objective
To evaluate the efficacy and safety of ravulizumab, a long-acting terminal complement (C5) inhibitor, in adult patients with AQP4-positive neuromyelitis optica spectrum disorder (NMOSD)
Study Summary
• Ravulizumab enables 8-week dosing interval vs 2 weeks for eculizumab
• Safety profile consistent with eculizumab; 2 meningococcal infections occurred, both recovered fully
Intervention
Ravulizumab IV weight-based loading dose (2,400-3,000mg) on day 1, maintenance dose (3,000-3,600mg) on day 15, then every 8 weeks vs external placebo control from PREVENT trial
Inclusion Criteria
Adults ≥18 years with AQP4+ NMOSD per 2015 criteria, ≥1 relapse in 12 months before screening, EDSS ≤7
Study Design
Arms: Ravulizumab vs External Placebo (PREVENT trial)
Patients per Arm: 58 vs 47
Outcome
• HAI worsening significantly lower: 3.4% vs 23.4% (p=0.0228)
• EDSS worsening numerically lower: 10.3% vs 23.4% (p=0.0588, NS due to hierarchical testing)
Bottom Line
Ravulizumab (long-acting C5 complement inhibitor, Ultomiris) significantly reduced risk of relapse in AQP4-IgG+ NMOSD: 0 relapses in ravulizumab group vs 20% relapse rate in placebo at prespecified interim analysis (P<0.001). Trial stopped early for overwhelming efficacy. Published Lancet Neurology 2023. 58 patients. Q8-week dosing (vs eculizumab Q2-week).
Major Points
- Zero relapses in ravulizumab group vs 20% placebo at interim analysis (P<0.001). Stopped early for efficacy.
- Time to first relapse: primary endpoint. HR not estimable (no events in treatment arm).
- 58 patients with AQP4-IgG+ NMOSD. Randomized 2:1 (ravulizumab 39 : placebo 19).
- Ravulizumab: long-acting anti-C5 complement antibody. Loading dose then Q8-week maintenance IV.
- Advantage over eculizumab: Q8-week dosing vs Q2-week — major convenience improvement.
- Complete complement suppression: terminal complement activity undetectable throughout treatment.
- AEs: headache, UTI, upper respiratory. Meningococcal vaccination required (same as eculizumab).
- Published Lancet Neurology 2023 (Pittock et al.). Alexion/AstraZeneca sponsored.
- FDA approved ravulizumab for NMOSD 2024 — third complement inhibitor for NMOSD after eculizumab.
- NMOSD is C5b-9/MAC-mediated astrocytopathy — complement inhibition targets core pathophysiology.
Study Design
Primary Outcome
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| - |