A Study to Test How Safe Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Alone Are and How Well They Work in Adult Patients With Generalized Myasthenia Gravis (NIMBLE)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Generalized Myasthenia Gravis

Treatments: Drug: Pozelimab; Drug: Pozelimab + Cemdisiran; Drug: Cemdisiran; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05070858

2023-508842-17-00 (Registry Identifier)

2020-003272-41 (EudraCT Number)

R3918-MG-2018

Details and patient eligibility

About

This study is researching the experimental drugs called pozelimab and cemdisiran, and cemdisiran monotherapy. The study is focused on patients with generalized myasthenia gravis (gMG). Myasthenia gravis is a disease that causes weakness and fatigue in muscles in the body because the nerves and muscles are not communicating properly. 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 with gMG.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drugs
• How the study drugs work inside the body
• How much study drugs are in the blood at different times
• Whether the body makes antibodies against pozelimab and cemdisiran (which could make the drugs less effective or could lead to side effects)

Full description

DBTP- Double blind treatment period (24 weeks) ETP - Extension treatment period (28 weeks) OLTP- Open label treatment period (68 weeks) Off-treatment follow up period (52 weeks)

Enrollment: 335 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Male or female patients ≥18 years of age at screening (or ≥ legal age of adulthood based on local regulations, whichever is older)
2. Patient with documented diagnosis of myasthenia gravis (MG) based on medical history and supported by previous evaluations as described in the protocol
3. Documented prior history of positive serologic test or a positive result during screening of anti-acetylcholine receptor (AChR) antibodies or anti-LRP4 antibodies.
4. Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to IVa at screening
5. Myasthenia Gravis-Activities of Daily Living (MG-ADL) score ≥6 at screening. Ocular items should not contribute more than 50% of MG-ADL total score as described in the protocol
6. Currently receiving an acetylcholinesterase inhibitor or documented reason for not using acetylcholinesterase inhibitor therapy per investigator
7. Currently receiving an immunosuppressive therapy (IST) for MG, or documented reason why the patient is not taking an IST per investigator
8. If currently receiving an IST, not anticipated to have IST dosage changed before randomization or during double-blind treatment period (DBTP).
9. Willing and able to comply with clinic visits and study-related procedures, including completion of the primary series of the meningococcal vaccinations required per protocol

Key Exclusion Criteria:

1. Patients with antibody profile that is only positive for muscle specific tyrosine kinase (MuSK) (MuSK positivity is based on a documented prior history of positive serologic test for antibodies to MuSK or a positive result during screening
2. History of thymectomy within 12 months prior to screening or planned during the study
3. History of malignant thymoma (patients with stage 1 may be enrolled), or history of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
4. Myasthenic crisis or Myasthenia Gravis Foundation of America (MGFA) Class V within 1 month of screening
5. Not meeting meningococcal vaccination requirements and, at a minimum, documentation of quadrivalent meningococcal vaccination within 5 years prior to randomization and serotype B vaccine (when available) within 3 years prior to randomization as described in the protocol
6. Known contraindication to meningococcal vaccines (group ACWY conjugate and group B vaccines) as described in the protocol
7. 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
8. Positive hepatitis B surface antigen or hepatitis C virus ribonucleic acid (RNA) during screening. NOTE: Cases with unclear interpretation should be discussed with the medical monitor
9. History of HIV infection or a positive test at screening per local requirements

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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335 participants in 4 patient groups

Group 1

Experimental group

Description:

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

Treatment:

Other: Placebo

Drug: Cemdisiran

Drug: Pozelimab + Cemdisiran

Group 2

Experimental group

Description:

Combination regimen throughout the study

Treatment:

Drug: Pozelimab + Cemdisiran

Group 3

Experimental group

Description:

Cemdisiran throughout the study

Treatment:

Drug: Cemdisiran

Group 4

Experimental group

Description:

Pozelimab monotherapy in DBTP followed by combination in ETP and OLTP

Treatment:

Drug: Pozelimab