Pozelimab + Cemdisiran for Myasthenia Gravis

(NIMBLE Trial)

Not currently recruiting at 204 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Regeneron Pharmaceuticals

Must be taking: Acetylcholinesterase inhibitors, Immunosuppressive therapy

Disqualifiers: MuSK antibodies, Recent thymectomy, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two experimental drugs, pozelimab and cemdisiran, to assess their effectiveness in treating generalized myasthenia gravis (gMG), a condition that causes muscle weakness and fatigue. Researchers aim to understand the effectiveness of these drugs both together and separately. They will also examine possible side effects, how the drugs function in the body, and whether the body creates antibodies that might reduce the drugs' effectiveness. Individuals with a documented diagnosis of myasthenia gravis, a history of positive tests for specific antibodies, and significant daily life challenges due to the condition might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, if you are on an immunosuppressive therapy (IST), you should not change the dosage before or during the treatment period.

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

Research has shown that the combination of pozelimab and cemdisiran is generally safe and well-tolerated by patients. One study found that this combination effectively managed symptoms without causing serious side effects.

Cemdisiran, when used alone, also demonstrated good safety results. Patients experienced a significant reduction in symptoms, and the treatment was well-tolerated over time.

Pozelimab, tested separately, showed positive safety outcomes. Previous studies found it effective without leading to major side effects.

Overall, these treatments have undergone advanced trials, indicating they have already passed earlier safety tests. This suggests they are generally safe, but individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Pozelimab and Cemdisiran for treating Myasthenia Gravis because they offer new approaches compared to standard treatments like acetylcholinesterase inhibitors and immunosuppressants. Pozelimab is unique because it targets the complement system, which plays a role in the immune response, potentially reducing symptoms more effectively. Cemdisiran works by specifically silencing certain genes involved in the disease process, which could lead to fewer side effects than traditional therapies. This combination of targeting both the complement system and gene silencing offers a promising alternative to current options.

What evidence suggests that this trial's treatments could be effective for myasthenia gravis?

Research shows that the drugs pozelimab and cemdisiran may help treat generalized myasthenia gravis (gMG). In this trial, participants will join different treatment groups. Some will receive cemdisiran alone, which has significantly improved patients' ability to perform daily activities. Others will receive a combination of pozelimab and cemdisiran, which has been effective without needing to completely block a part of the immune system that can mistakenly attack the body. Additionally, some participants will receive pozelimab alone, which achieved its main goals in clinical trials, suggesting it could be effective. Overall, these treatments have shown clear benefits in managing gMG symptoms. ^{1 2 6 7 8}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

Adults over 18 with a confirmed diagnosis of myasthenia gravis (MG), specifically those who have MGFA Class II to IVa and an MG-ADL score ≥6. Participants should be on or have a reason for not using acetylcholinesterase inhibitors or immunosuppressive therapy, without plans to change dosages during the trial. Exclusions include MuSK-only positive patients, recent thymectomy, certain cancer histories, HIV infection, no recent meningococcal vaccination unless planned before treatment starts.

Inclusion Criteria

I am on immunosuppressive therapy for myasthenia gravis or have a reason for not taking it.

You have tested positive for certain antibodies related to muscle and nerve function in the past.

I have been diagnosed with myasthenia gravis based on my medical history.

Exclusion Criteria

I haven't had a meningococcal vaccine in the last 5 years, but I'm willing to get one during screening.

I cannot use certain antibiotics for meningococcal disease prevention due to allergies or side effects.

I had or will have surgery to remove my thymus gland within the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double Blind Treatment Period (DBTP)

Participants receive either placebo or active treatment in a double-blind manner

24 weeks

Extension Treatment Period (ETP)

Participants are re-randomized to receive combination therapy or cemdisiran

28 weeks

Open Label Treatment Period (OLTP)

Participants receive open-label treatment with combination therapy

68 weeks

Off-treatment Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cemdisiran
• Pozelimab

Trial Overview The study is testing how well Pozelimab combined with Cemdisiran improves daily functioning affected by MG symptoms compared to each drug alone and placebo. It also looks at muscle strength, quality of life improvements, safety/tolerability of the drugs, their levels in blood/plasma and effects on immune response.

How Is the Trial Designed?

Group I: Group 4 Experimental Treatment 1 Intervention

Pozelimab monotherapy in DBTP followed by combination in ETP and OLTP

Group II: Group 3 Experimental Treatment 1 Intervention

Cemdisiran throughout the study

Group III: Group 2 Experimental Treatment 1 Intervention

Combination regimen throughout the study

Group IV: Group 1 Experimental Treatment 3 Interventions

Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

Eculizumab has shown efficacy and safety in treating refractory generalized myasthenia gravis (gMG) in Phase II and III studies, potentially offering a new immunosuppressive approach that could reduce the need for corticosteroids.

The drug works by blocking C5, which protects the neuromuscular junction from damage caused by autoantibodies, suggesting it could modify the disease course and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eculizumab for the treatment of myasthenia gravis. Mantegazza, R., Cavalcante, P.[2021]

In a 26-week phase 3 study, eculizumab significantly improved symptoms in patients with refractory generalized myasthenia gravis (gMG), with 21.4% of treated patients achieving 'minimal symptom expression' compared to only 1.7% in the placebo group.

The benefits of eculizumab were sustained over a 130-week open-label extension, showing that patients who initially received placebo also achieved similar symptom relief after starting eculizumab, indicating its long-term efficacy and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

'Minimal symptom expression' in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab. Vissing, J., Jacob, S., Fujita, KP., et al.[2021]

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]

Eculizumab significantly improved outcomes in patients with anti-acetylcholine receptor-positive refractory generalized myasthenia gravis (gMG), with 25.0% achieving minimal manifestations (MM) after 26 weeks compared to 13.3% in the placebo group.

After 130 weeks of treatment, 88.0% of patients on eculizumab reported improved status, and 57.3% achieved MM, demonstrating both rapid and sustained efficacy without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension. Mantegazza, R., Wolfe, GI., Muppidi, S., et al.[2021]

Pozelimab is a newly approved monoclonal antibody that blocks complement factor 5 (C5) and is the first FDA-approved treatment for CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE disease, in both adults and children aged 1 year and older.

In addition to its approval for PLE, pozelimab has received orphan drug designations for treating paroxysmal nocturnal hemoglobinuria (PNH) and myasthenia gravis, indicating its potential for broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pozelimab: First Approval. Hoy, SM.[2023]

About 10% of myasthenia gravis (MG) patients do not respond well to current treatments and are considered treatment refractory, with certain factors like being anti-MuSK positive or having a history of thymoma increasing this risk.

New therapies, including monoclonal antibodies like rituximab, eculizumab, and belimumab, are being proposed for patients who do not respond to standard treatments, aiming to improve outcomes for those with treatment-refractory MG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When myasthenia gravis is deemed refractory: clinical signposts and treatment strategies. Mantegazza, R., Antozzi, C.[2022]

Eculizumab demonstrated significant efficacy in treating two out of three patients with refractory MGFA class V generalized myasthenia gravis (gMG), leading to marked improvements in their clinical scores after treatment.

The two responsive patients achieved minimal manifestation status within 4 to 6 weeks, while the third patient showed only a partial response, indicating that eculizumab may be beneficial but results can vary among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of eculizumab in ventilator-dependent myasthenia gravis patients. Usman, U., Chrisman, C., Houston, D., et al.[2021]

A new sum score has been developed to define treatment-refractory generalized myasthenia gravis (TRgMG), which includes criteria such as disease severity and inefficacy of previous therapies, making it easier for clinicians to make treatment decisions.

This scoring system, created through a consensus of 12 experts and based on a thorough literature review, aims to clarify when eculizumab should be used and can also serve as a basis for inclusion criteria in future clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Sum Score to Define Therapy-Refractory Myasthenia Gravis: A German Consensus. Schroeter, M., Berger, B., Blaes, F., et al.[2022]

Citations

1. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/regeneron-announces-positive-results-phase-3-trial-generalized

Regeneron Announces Positive Results from Phase 3 Trial ... Cemdisiran monotherapy, dosed subcutaneously every three months, met the primary and key secondary endpoints, showing a 2.3-point ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05070858

NCT05070858 | A Study to Test How Safe Pozelimab and ... The aim of the study is to see how effective pozelimab and cemdisiran are when used in combination and when pozelimab and cemdisiran are used alone for patients ...

3. clinicaladvisor.com clinicaladvisor.com/news/cemdisiran-looks-promising-for-generalized-myasthenia-gravis-2/

Cemdisiran Looks Promising for Generalized Myasthenia ... Treatment with cemdisiran monotherapy resulted in an average of 74% complement inhibition, while the combination treatment led to nearly 99% ...

4. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/nimble-trial-demonstrates-cemdisiran-efficacy-generalized-myasthenia-gravis

Phase III NIMBLE Trial Demonstrates Cemdisiran Efficacy ... Cemdisiran monotherapy improved MG-ADL scores, meeting primary and key secondary endpoints in the NIMBLE trial for generalized myasthenia gravis ...

5. practicalneurology.com practicalneurology.com/news/sirna-treatment-shows-efficacy-for-generalized-myasthenia-gravis/2483216/

siRNA Treatment Shows Efficacy for Generalized Myasthenia ... Outcomes were assessed at 24 weeks using the ... Regeneron announces positive results from phase 3 trial in generalized myasthenia gravis.

6. rheumatologyadvisor.com rheumatologyadvisor.com/news/cemdisiran-looks-promising-for-generalized-myasthenia-gravis/

Cemdisiran Looks Promising for Generalized Myasthenia ... Treatment with cemdisiran monotherapy resulted in an average of 74% complement inhibition, while the combination treatment led to nearly 99% ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10435727/

Results of a phase 1/2 study of cemdisiran in healthy ... Previously reported results showed sustained reduction in C5 levels following cemdisiran monotherapy, with >90% reduction in patients with PNH.

8. clinicaltrialsarena.com clinicaltrialsarena.com/analyst-comment/phase-iii-regeneron-pozelimab-cemdisiran-mg/

Phase III success for Regeneron signals pozelimab and ... The results showed that both cemdisiran monotherapy and pozelimab + cemdisiran combination therapy met their primary endpoints, displaying a ...