Vivacity-MG
Safety and Efficacy of Nipocalimab in Patients With Generalized Myasthenia Gravis: Results From the Randomized Phase 2 Vivacity-MG Study
Clinical Question
Does IV nipocalimab, an anti-FcRn monoclonal antibody, safely improve symptoms in adults with generalized myasthenia gravis who have inadequate response to standard-of-care therapy?
Bottom Line
In this phase 2 study, nipocalimab was generally safe, well-tolerated, and demonstrated a statistically significant dose-dependent reduction in MG-ADL at day 57 (p = 0.031) when added to standard-of-care therapy in gMG, supporting further evaluation in phase 3 trials.
Major Points
- Statistically significant dose response in MG-ADL change from baseline to day 57 (p = 0.031, linear trend test) across placebo, 5 mg/kg Q4W, 30 mg/kg Q4W, and 60 mg/kg Q2W arms
- No individual nipocalimab dose significantly improved MG-ADL vs placebo at day 57
- TEAE rates similar between combined nipocalimab (83.3%) and placebo (78.6%) groups
- Infection rates 33.3% (nipocalimab) vs 21.4% (placebo); no grade ≥3 infections or hypoalbuminemia
- No deaths and no discontinuations due to TEAEs with nipocalimab
- Supports phase 3 development of nipocalimab for gMG
Design
Study Type: Multicenter, randomized, double-blind, placebo-controlled, phase 2 study
Randomization: 1
Blinding: Double-blind (patients, investigators, sponsor, and site personnel blinded); permuted block randomization stratified by autoantibody type (anti-AChR vs anti-MuSK) and baseline MG-ADL score (≤10, >10) for anti-AChR positive patients
Allocation: 1:1:1:1:1 to placebo Q2W, nipocalimab 5 mg/kg Q4W, 30 mg/kg Q4W, 60 mg/kg single dose, or 60 mg/kg Q2W
Enrollment Period: First patient dosed April 10, 2019
Follow-up Duration: 8-week double-blind treatment period followed by 8-week posttreatment follow-up (4-week screening period preceding)
Centers: 38
Countries: United States, Canada, Germany, Italy, Poland, Spain, Belgium, United Kingdom
Sample Size: 68
Analyzed: 57
Analysis: Linear trend test over placebo, nipocalimab 5 mg/kg Q4W, 30 mg/kg Q4W, and 60 mg/kg Q2W groups for the primary efficacy endpoint; mixed-effects model for repeated measures (MMRM) referenced
Power Calculation: ≥80% power with 1-sided type 1 error of 5% to detect dose response in MG-ADL change at day 57; assumed change from baseline of −2 (placebo) and −6 (60 mg/kg Q2W) with common SD of 3; planned sample of 60 (12 per arm) assuming 10 evaluable patients per arm with 15% attrition
Registration: NCT03772587; EudraCT 2018-002247-28
Inclusion Criteria
- Adults aged ≥18 years
- History and clinical symptoms of generalized myasthenia gravis
- Diagnosis confirmed by positive serology for anti-AChR or anti-MuSK autoantibodies
- Insufficient symptom control defined as QMG score ≥12 AND MG-ADL score ≥4 despite stable SOC therapy
- MGFA Clinical Classification Class II, III, or IVa
- Women of childbearing potential: negative serum pregnancy test at screening, negative urine pregnancy test at baseline, and abstinence or effective contraception during the study and 30 days after last study treatment
Exclusion Criteria
- Receiving a systemic biologic antibody for any concurrent disease
- Rituximab or eculizumab use within 12 months before screening
- Plasmapheresis, immunoadsorption therapy, or IVIG within 6 weeks before randomization
- Clinically significant acute or chronic infection
- Unresected thymoma or history of malignant thymoma
- Thymectomy within 12 months before screening
- Serum IgG (unless attributed to immunomodulators), albumin, or calcium levels outside the normal range
Arms
| Field | Control | Nipocalimab 5 mg/kg Q4W | Nipocalimab 30 mg/kg Q4W | Nipocalimab 60 mg/kg single dose | Nipocalimab 60 mg/kg Q2W | Combined Nipocalimab |
|---|---|---|---|---|---|---|
| N | 14 | 0 | 0 | 0 | 0 | 54 |
| Intervention | IV placebo (5% dextrose in water) every 2 weeks, 5 infusions over 8 weeks, plus background standard-of-care therapy | IV nipocalimab 5 mg/kg every 4 weeks (placebo on alternate visits to maintain blinding), plus background SOC therapy | IV nipocalimab 30 mg/kg every 4 weeks (placebo on alternate visits), plus background SOC therapy | IV nipocalimab 60 mg/kg single dose followed by placebo at subsequent visits, plus background SOC therapy | IV nipocalimab 60 mg/kg every 2 weeks, 5 infusions over 8 weeks, plus background SOC therapy | All nipocalimab arms pooled |
| Duration | 8 weeks | 8 weeks | 8 weeks | 8 weeks | 8 weeks | 8 weeks |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Change from baseline to day 57 in MG-ADL total score; dose response assessed by linear trend test over placebo, 5 mg/kg Q4W, 30 mg/kg Q4W, and 60 mg/kg Q2W | Primary | Statistically significant dose response (no individual nipocalimab dose vs placebo was significant) | 0.031 (linear trend test) | ||
| Correlation between change in total MG-ADL score and total serum IgG reduction from baseline | Secondary | Not reported in source text | |||
| Change from baseline to day 57 in QMG score | Secondary | Not reported in source text | |||
| Change from baseline to day 57 in MG-QoL 15 score | Secondary | Not reported in source text | |||
| Shift in MGFA classification from baseline to day 57 | Secondary | Not reported in source text | |||
| Incidence of TEAEs (combined nipocalimab vs placebo) | Safety | 83.3% vs 78.6% | |||
| Infections (combined nipocalimab vs placebo) | Safety | 33.3% vs 21.4% | |||
| Grade ≥3 infections (AESI) | Safety | None with nipocalimab | |||
| Grade ≥3 hypoalbuminemia (albumin <2 g/dL; AESI) | Safety | None with nipocalimab | |||
| Deaths | Safety | None | |||
| Discontinuations due to TEAEs | Safety | None | |||
| Combined Nipocalimab TEAEs | Adverse | 83.3% | |||
| Placebo TEAEs | Adverse | 78.6% | |||
| Combined Nipocalimab Infections | Adverse | 33.3% | |||
| Placebo Infections | Adverse | 21.4% | |||
| Deaths | Adverse | 0 | |||
| Discontinuations due to TEAEs | Adverse | 0 | |||
| AESIs (grade ≥3 infection or hypoalbuminemia) | Adverse | 0 | |||
Subgroup Analysis
Exploratory PD and autoantibody analyses planned (anti-AChR vs anti-MuSK strata); specific subgroup efficacy results not detailed in source text
Criticisms
- Small sample size (N=68 randomized; 14 in placebo) limits power for individual dose comparisons
- Short 8-week treatment period may not capture long-term efficacy or safety signals
- No individual nipocalimab dose significantly improved MG-ADL vs placebo — only the linear dose-response trend was significant
- Only 4 anti-MuSK positive patients enrolled, limiting inference in this subgroup
- Class I evidence designation notes nipocalimab did not significantly improve MG-ADL at any individual dose
Funding
Janssen Research & Development, LLC (multiple authors are Janssen employees); Article Processing Charge funded by the authors
Based on: Vivacity-MG (Neurology, 2024)
Authors: Antozzi C, Guptill J, Bril V, ..., for the Vivacity-MG Phase 2 Study Group
Citation: Neurology 2024;102:e207937. doi:10.1212/WNL.0000000000207937
Content summarized and formatted by NeuroTrials.ai.