What side effects are associated with this type of intervention?

Common treatments for Myasthenia Gravis include acetylcholinesterase inhibitors, corticosteroids, immunosuppressants, and monoclonal antibodies targeting the complement system, such as eculizumab. Acetylcholinesterase inhibitors can cause gastrointestinal issues, muscle cramps, and increased salivation. Corticosteroids and immunosuppressants may lead to weight gain, hypertension, diabetes, and increased infection risk. Monoclonal antibodies like eculizumab, which target C5 similar to Pozelimab, can cause headaches, upper respiratory infections, and an increased risk of meningococcal infections. RNAi therapeutics like Cemdisiran, which target C5 synthesis, may have side effects including injection site reactions and potential immune-related effects.

What prior FDA approvals exist?

Eculizumab, a monoclonal antibody that inhibits complement component C5, was the first FDA-approved drug for Myasthenia Gravis in 2017, specifically for patients with anti-acetylcholine receptor antibody-positive generalized MG. This approval was significant as it targeted the complement system to reduce the autoimmune attack on neuromuscular junctions. Other treatments for MG include immunosuppressants and acetylcholinesterase inhibitors, but these do not target the complement system like Eculizumab, Pozelimab, and Cemdisiran.

What other types of research exist?

Promising alternatives to Pozelimab + Cemdisiran for Myasthenia Gravis patients include Eculizumab, a C5 inhibitor already used in other autoimmune conditions. Other potential treatments could involve novel monoclonal antibodies or RNAi therapeutics targeting different components of the immune system or complement pathway. Consulting with a healthcare provider for the latest clinical trial data and approved therapies is recommended.

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siRNA

Pozelimab + Cemdisiran for Myasthenia Gravis (NIMBLE Trial)

Phase 3

Recruiting

Research Sponsored by Regeneron Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Currently receiving an immunosuppressive therapy (IST) for MG, or documented reason why the patient is not taking an IST per investigator

Patient with documented diagnosis of myasthenia gravis (MG) based on medical history and supported by previous evaluations as described in the protocol

Must not have

Patients who require antibiotics for meningococcal prophylaxis and have a contraindication, warning, or precaution precluding the use of penicillin class and penicillin-alternative antibiotics planned to be used for prophylaxis, or a history of intolerance leading to the discontinuation of these antibiotics

History of HIV infection or a positive test at screening per local requirements

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 24

Awards & highlights

Pivotal Trial

Summary

This trial is testing two medications, pozelimab and cemdisiran, to help people with generalized myasthenia gravis (gMG), a condition that causes muscle weakness. The study aims to see if these drugs can improve daily functioning and muscle strength by calming down an overactive immune system. The trial will also check the safety of these treatments.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects are not listed here, participants will be monitored for general safety and tolerability which typically includes tracking any adverse reactions like allergic responses or infusion-related issues that may arise from the treatments.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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My myasthenia gravis is moderate to severe but not requiring a ventilator.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have HIV or tested positive for HIV.

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I am allergic or cannot have meningococcal vaccines due to health reasons.

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My tests show I have antibodies against MuSK.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 24

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 24

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 24 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score

Secondary study objectives

Change from baseline in Myasthenia Gravis Quality of Life (MG QOL15r) total score

Change from baseline in Quantitative Myasthenia Gravis (QMG) score

Change from baseline in the Myasthenia Gravis Composite (MGC) total score

+6 more

Side effects data

From 2024 Phase 2 & 3 trial • 10 Patients • NCT04209634

20%

Rhinitis

20%

Iron deficiency

20%

Urticaria

20%

Pyrexia

10%

Vomiting

10%

Dehydration

10%

Acarodermatitis

10%

Nasopharyngitis

10%

Tonsillitis

10%

Hypokalaemia

10%

Metabolic acidosis

10%

Alopecia

10%

Alopecia areata

10%

Dermatitis contact

10%

Abdominal pain

10%

Constipation

10%

Gingival bleeding

10%

Blood glucose increased

10%

Blood uric acid increased

10%

Hepatic enzyme increased

10%

Anaemia folate deficiency

10%

Immunisation reaction

10%

Headache

10%

Haematuria

10%

Proteinuria

100%

80%

60%

40%

20%

Study treatment Arm

Pozelimab

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Group 4Experimental Treatment1 Intervention

Pozelimab monotherapy in DBTP followed by combination in ETP and OLTP

Group II: Group 3Experimental Treatment1 Intervention

Cemdisiran throughout the study

Group III: Group 2Experimental Treatment1 Intervention

Combination regimen throughout the study

Group IV: Group 1Experimental Treatment3 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pozelimab

2020

Completed Phase 3

~130

Cemdisiran

2020

Completed Phase 2

~80

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Myasthenia Gravis (MG) include acetylcholinesterase inhibitors, immunosuppressants, and monoclonal antibodies. Acetylcholinesterase inhibitors, such as pyridostigmine, increase the availability of acetylcholine at the neuromuscular junction, improving muscle contraction. Immunosuppressants like corticosteroids and azathioprine reduce the immune system's attack on acetylcholine receptors. Monoclonal antibodies, such as eculizumab, target components of the immune system like the complement protein C5, preventing the formation of the membrane attack complex that damages the neuromuscular junction. Pozelimab, a monoclonal antibody targeting C5, and Cemdisiran, an RNAi therapeutic targeting C5 synthesis, work by inhibiting the complement pathway, thereby reducing inflammation and damage at the neuromuscular junction. These mechanisms are crucial for MG patients as they help to alleviate muscle weakness and improve daily functioning.