Nipocalimab for Myasthenia Gravis

Not currently recruiting at 163 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Immunodeficiency, MGFA Class I/V, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 24

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called nipocalimab, an anti-FcRn monoclonal antibody, for individuals with generalized myasthenia gravis (gMG), a condition that causes muscle weakness. The study aims to evaluate the effectiveness and safety of nipocalimab compared to a placebo, which is a harmless substance resembling the drug. It will also compare the drug's effects when injected under the skin versus through a vein. Participants with noticeable muscle weakness due to gMG, who struggle with everyday activities, might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that nipocalimab, administered either as an injection under the skin or directly into a vein, is generally well-tolerated by patients with generalized myasthenia gravis (gMG). Previous tests indicate that most patients did not experience serious side effects. Common side effects were mild, including headaches and reactions at the injection site. This suggests the treatment is usually safe for most people, though individual experiences may vary. Always discuss potential risks with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myasthenia gravis?

Unlike the standard of care for myasthenia gravis, which typically includes treatments like acetylcholinesterase inhibitors, corticosteroids, and immunosuppressants, nipocalimab offers a unique approach. Nipocalimab is designed to block the neonatal Fc receptor (FcRn), potentially reducing the levels of harmful antibodies that attack the neuromuscular junctions in myasthenia gravis. Researchers are excited about nipocalimab because it represents a targeted therapy that could offer faster and more sustained relief by addressing the underlying antibody-related mechanisms of the disease. Moreover, it offers both intravenous and subcutaneous delivery options, providing flexibility and convenience in administration.

What evidence suggests that nipocalimab might be an effective treatment for myasthenia gravis?

Research has shown that nipocalimab can greatly improve symptoms for people with generalized myasthenia gravis (gMG). Studies have found that it quickly and consistently lowers certain antibodies in the body, which helps control symptoms more effectively. In this trial, participants will receive either nipocalimab or a placebo. One study found that after 10 weeks, patients taking nipocalimab showed significant improvement in their ability to perform daily activities, with better symptom scores compared to other treatments. These improvements lasted for up to six months, indicating that nipocalimab can help keep symptoms under control over time. This evidence suggests that nipocalimab is a promising option for managing gMG. ^{6 7 8 9 10}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

Adults with generalized myasthenia gravis (MG) who have a certain level of muscle weakness and can undergo infusions and blood sampling. Women must not be pregnant, and men agree to not donate sperm during the study. Participants should not have had recent thymectomy or MG crisis, nor should they have heart issues or allergies to the trial drug.

Inclusion Criteria

You have difficulty with everyday activities due to Myasthenia Gravis, with a score of 6 or higher on the MG-ADL test.

A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test at Day 1 prior to administration of study intervention

I can receive medication through a vein and provide blood samples as needed.

Exclusion Criteria

I have mild or very severe myasthenia gravis, or had a crisis recently.

I had my thymus gland removed within the last year or plan to have it removed.

I have had a heart attack, unstable heart disease, or stroke in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Placebo-controlled Phase

Participants receive either nipocalimab or placebo via IV infusion every 2 weeks

24 weeks

12 visits (in-person)

Open-label Extension (OLE) Phase

Participants who complete the double-blind phase continue to receive nipocalimab every 2 weeks

24 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nipocalimab
• Placebo

Trial Overview The trial is testing nipocalimab's effectiveness compared to a placebo in improving symptoms of generalized myasthenia gravis. Patients will receive either the actual medication or a placebo without knowing which one they are getting.

How Is the Trial Designed?

Group I: Nipocalimab Subcutaneous (SC) Experimental Treatment 1 Intervention

OLE Phase: Participants from Cohort 1 will receive nipocalimab subcutaneous liquid in vial (SC-LIV) qw until Week 8. Participants with gMG from Cohort 2 who have not received nipocalimab previously, will receive nipocalimab SC-LIV until Week 8. Participants who complete the 8-week treatment period will have the opportunity to continue receiving nipocalimab SC-LIV qw in the Long term extension (LTE) period.

Group II: Nipocalimab Experimental Treatment 1 Intervention

Double-blind Placebo-controlled Phase: Participants will receive nipocalimab intravenous (IV) infusions once every 2 weeks (q2w) up to 24 weeks during double-blind placebo-controlled phase. Open-label Extension (OLE) Phase: Participants who complete the double-blind placebo-controlled phase will enter the OLE phase and continue to receive nipocalimab q2w IV infusion till study end.

Group III: Placebo Placebo Group 1 Intervention

Double-blind Placebo-controlled Phase: Participants will receive matching placebo of nipocalimab IV infusion q2w up to 24 weeks during double-blind placebo-controlled phase.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

In a phase 2 study involving 44 patients with moderate-to-severe myasthenia gravis (MG), iscalimab demonstrated significant improvements in the MG Composite score and MG-Activities of Daily Living score compared to placebo, particularly in non-thymectomized patients.

The safety profile of iscalimab was comparable to placebo, with similar rates of adverse events, indicating that it may be a safe option for patients with MG despite not showing a protective effect overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of iscalimab, a novel anti-CD40 monoclonal antibody, in moderate-to-severe myasthenia gravis: A phase 2 randomized study. GomezMancilla, B., Meriggioli, MN., Genge, A., et al.[2023]

The FDA has recently approved new therapies, including complement and Fc receptor inhibitors, for treating generalized myasthenia gravis, highlighting advancements in treatment options for this condition.

There is ongoing uncertainty regarding which patients will benefit most from these expensive therapies, prompting discussions on the need for better clinical trial readiness and biomarker development to guide future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The best and worst of times in therapy development for myasthenia gravis. Benatar, M., Cutter, G., Kaminski, HJ.[2023]

In a subgroup of patients with treatment-refractory generalized myasthenia gravis who had previously received chronic intravenous immunoglobulin (IVIg), eculizumab demonstrated sustained clinical improvements over 18 months compared to placebo.

Eculizumab was associated with a lower rate of disease exacerbations and was well tolerated, indicating its efficacy and safety for patients transitioning from IVIg treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to eculizumab in patients with myasthenia gravis recently treated with chronic IVIg: a subgroup analysis of REGAIN and its open-label extension study. Jacob, S., Murai, H., Utsugisawa, K., et al.[2022]

In a phase 2a trial involving 43 patients with generalized myasthenia gravis, rozanolixizumab showed a trend towards clinical benefit, particularly in secondary measures like the MG-Activities of Daily Living and MG-Composite scores, although the primary endpoint (QMG score) did not reach statistical significance.

Rozanolixizumab was generally well tolerated, with headache being the most common adverse event, occurring in 57% of patients receiving the treatment compared to 14% in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Rozanolixizumab in Moderate to Severe Generalized Myasthenia Gravis: A Phase 2 Randomized Control Trial. Bril, V., Benatar, M., Andersen, H., et al.[2021]

In a Phase 2a trial involving 17 patients with generalized myasthenia gravis, batoclimab significantly reduced total immunoglobulin G and anti-acetylcholine receptor antibodies compared to placebo, indicating its potential efficacy in targeting the underlying immune response.

The study found no safety issues with batoclimab, supporting its tolerability and suggesting it could be a viable option for patient-administered therapy in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous batoclimab in generalized myasthenia gravis: Results from a Phase 2a trial with an open-label extension. Nowak, RJ., Breiner, A., Bril, V., et al.[2023]

In a study of 30 patients with refractory myasthenia gravis (MG) treated with rituximab for an average of 33.3 months, significant improvements were observed in disease severity, as indicated by a decrease in the quantitative myasthenia gravis (QMG) score from 11 to 4.3 (p < 0.001).

Rituximab was found to be safe and well-tolerated, with no crises or deaths reported, and 93.1% of patients were able to reduce their daily steroid dose to 10 mg or less, highlighting its potential as a long-term treatment option for anti-AChR+ and double seronegative MG patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab as a sole steroid-sparing agent in generalized myasthenia gravis: Long-term outcomes. Kefalopoulou, ZM., Veltsista, D., Germeni, A., et al.[2023]

Myasthenia gravis (MG) is driven by IgG antibodies that attack acetylcholine receptors, leading to muscle weakness, and current treatments like corticosteroids are not very specific.

New therapies targeting IgG Fc mechanisms, such as FcRn-targeting agents, are being developed and show promise for more effective and personalized treatments that could lead to sustained remission in MG patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fc-Receptor Targeted Therapies for the Treatment of Myasthenia gravis. Keller, CW., Pawlitzki, M., Wiendl, H., et al.[2021]

Citations

1. jnj.com jnj.com/media-center/press-releases/johnson-johnson-announces-first-head-to-head-study-comparing-imaavy-with-an-alternative-fcrn-blocker-in-generalized-myasthenia-gravis-gmg-at-aanem-annual-meeting

The EPIC study will evaluate treatment with IMAAVY ... The study's key primary and secondary endpoints are change from baseline in total immunoglobulin G (IgG) levels and sustained disease control ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10962909/

Safety and Efficacy of Nipocalimab in Patients With ... The primary efficacy endpoint was change from baseline to day 57 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total scores. Dose ...

3. neurologylive.com neurologylive.com/view/newly-unveiled-epic-trial-pins-myasthenia-gravis-medications-nipocalimab-against-efgartigimod-efficacy

Newly Unveiled EPIC Trial Pins Myasthenia Gravis ... For another comparator, results at 10 weeks showed that nipocalimab displayed a mean difference of -2.38 at 7mg/kg (95% CI, -3.57 to -1.18; P <.

4. institut-myologie.org institut-myologie.org/en/2025/03/04/positive-phase-iii-results-for-nipocalimab-in-generalised-myasthenia-gravis/

Positive phase III results for nipocalimab in generalised ... A rapid and sustained reduction in IgG, correlated with a greater improvement in symptoms, was observed with nipocalimab.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1474442224004988

Articles Safety and efficacy of nipocalimab in adults with ... This reduction resulted in clinically meaningful, sustained improvement in patients' symptoms up to 6 months.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/761430Orig1s000OtherR.pdf

761430Orig1s000 OTHER REVIEW(S) - accessdata.fda.gov Nipocalimab injection for intravenous use is being developed for the treatment of generalized myasthenia gravis (gMG) in adults and adolescent ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05265273

NCT05265273 | A Study of Nipocalimab in Children Aged ... The purpose of this study is to determine the effect of nipocalimab on total serum immunoglobulin G (IgG) in pediatric participants 2 to less than (<) 18 years ...

8. neurology.org neurology.org/doi/10.1212/WNL.0000000000203877

Nipocalimab Dose Selection for A Phase 3 Study in Adult ... Potential for nipocalimab efficacy in autoimmune diseases was demonstrated in a Phase 2 (Ph2) study in patients with generalized myasthenia gravis (gMG). Design ...

9. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/full/10.1002/psp4.70109

Nipocalimab Dose Selection in Generalized Myasthenia Gravis Nipocalimab (ImaavyTM; JNJ-80202135; M281), a fully human IgG1 monoclonal antibody (mAb), selectively binds to human FcRn with high affinity ...

10. io.nihr.ac.uk io.nihr.ac.uk/wp-content/uploads/2023/11/28008-Nipocalimab-for-Myasthenia-Gravis-V1.0-NOV2023-NON-CONF.pdf

Health Technology Briefing November 2023 Nipocalimab is currently in clinical development for the treatment of adults with generalised myasthenia gravis (gMG). gMG is a rare, long-term ...