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CHAMPION-NMOSD

Year of Publication: 2023

Link: https://www.neurology.org/doi/10.1212/WNL.0000000000202922

PDF: https://www.jns-journal.com/action/showP...%2823%2900518-X

Clinical Question

In adults with AQP4-IgG-positive neuromyelitis optica spectrum disorder, does ravulizumab (a long-acting terminal complement C5 inhibitor) reduce the risk of relapse compared with external placebo control from the PREVENT trial?

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.

      

Design

Arms

Field	Ravulizumab	Control
Intervention	Ravulizumab IV — weight-based loading dose (2,400–3,000 mg) on day 1, maintenance (3,000–3,600 mg) on day 15, then every 8 weeks	External placebo control from the PREVENT trial (matched patient-level data)
Duration	Open-label treatment period	Matched follow-up

Outcomes

Outcome	Type	Control	Intervention
Time to first adjudicated on-trial relapse in AQP4-IgG-positive NMOSD.	Primary
Any treatment-emergent AE (total)	Adverse	328 TEAEs in 47 patients (PREVENT placebo)	328 TEAEs in 58 patients (ravulizumab)
Treatment-emergent serious adverse events	Adverse		8 TESAEs in ravulizumab arm
COVID-19	Adverse		14 (24.1%)
Headache	Adverse	10 (21.3%)	14 (24.1%)
Back pain	Adverse	6 (12.8%)	7 (12.1%)
Arthralgia	Adverse		6 (10.3%)
Urinary tract infection	Adverse	9 (19.1%)	6 (10.3%)
Meningococcal infection	Adverse	0	2 (3.4%) - both recovered with treatment

Based on: CHAMPION-NMOSD (2023)

Reviewed by: Ahmed Koriesh, MD

Content summarized and formatted by NeuroTrials.ai.

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

• No patients on ravulizumab had adjudicated relapses vs 20/47 (43%) on placebo, representing 98.6% relapse risk reduction (p<0.0001)
• 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

• Primary: 0% vs 43% adjudicated relapses (HR 0.014, 95% CI 0.000-0.103, p<0.0001)
• 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

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

Definition: Time to first adjudicated on-trial relapse in AQP4-IgG-positive NMOSD.

Control	Intervention	HR/OR	P-value
-	-	-	-

Citation

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CHAMPION-NMOSD

Clinical Question

Bottom Line

Major Points

Design

Arms

Outcomes

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