Nipocalimab for Myasthenia Gravis

Recruiting at 111 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

196 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing nipocalimab, a medicine that blocks harmful proteins, in people with generalized myasthenia gravis to see if it can reduce their muscle weakness.

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.

What data supports the effectiveness of the drug Nipocalimab for treating myasthenia gravis?

Research shows that other drugs targeting the neonatal Fc receptor, like rozanolixizumab, have been effective in treating generalized myasthenia gravis, suggesting that Nipocalimab, which works similarly, may also be effective. ^{1 2 3 4 5}

What makes the drug Nipocalimab unique for treating myasthenia gravis?

Nipocalimab is unique because it targets the neonatal Fc receptor (FcRn), which plays a role in prolonging the lifespan of antibodies that contribute to myasthenia gravis. This approach is different from traditional treatments that use corticosteroids or immunosuppressants, offering a more specific way to reduce harmful antibodies in the body. ^{1 2 5 6 7}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: 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 II: 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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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]

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 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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Subcutaneous batoclimab in generalized myasthenia gravis: Results from a Phase 2a trial with an open-label extension. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The best and worst of times in therapy development for myasthenia gravis. [2023]

3. Scotland 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. [2023]

4. England 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Rozanolixizumab in Moderate to Severe Generalized Myasthenia Gravis: A Phase 2 Randomized Control Trial. [2021]

6. Italy pubmed.ncbi.nlm.nih.gov

Rituximab as a sole steroid-sparing agent in generalized myasthenia gravis: Long-term outcomes. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Fc-Receptor Targeted Therapies for the Treatment of Myasthenia gravis. [2021]