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A Study to Examine the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Symptomatic Generalized Myasthenia Gravis (NIMBLE)

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Regeneron Pharmaceuticals

Status and phase

Enrolling
Phase 3

Conditions

Generalized Myasthenia Gravis

Treatments

Drug: Pozelimab + Cemdisiran
Drug: Pozelimab
Other: Placebo
Drug: Cemdisiran

Study type

Interventional

Funder types

Industry

Identifiers

NCT05070858
2020-003272-41 (EudraCT Number)
R3918-MG-2018

Details and patient eligibility

About

The primary objective is: To evaluate the effect of pozelimab + cemdisiran on daily functioning that is impacted by signs and symptoms in patients with symptomatic generalized myasthenia gravis (gMG) The secondary objectives of the study are: To evaluate the effect of pozelimab + cemdisiran (ie, combination) and cemdisiran monotherapy on: Clinician-assessed signs of myasthenia gravis (MG) and muscle strength Daily functioning that is impacted by signs and symptoms in patients with symptomatic gMG (cemdisiran monotherapy only). Proportion of patients with improvements in daily function that is impacted by signs and symptoms of MG Proportion of patients that have improvements in clinician-assessed signs of MG and muscle strength Health related quality of life Proportion of patients with minimal MG symptoms Patient- and clinician-reported signs and symptoms of MG To evaluate the safety and tolerability of pozelimab + cemdisiran and cemdisiran monotherapy To assess the concentration of total pozelimab in serum To assess the concentrations of cemdisiran and its metabolites in plasma To assess the immunogenicity of pozelimab To assess the concentration of total C5 in plasma To assess the immunogenicity of cemdisiran To study the effect of pozelimab + cemdisiran and cemdisiran monotherapy on complement activation

Full description

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

Enrollment

235 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

  • Male or female patients ≥18 years of age at screening (or ≥ legal age of adulthood based on local regulations, whichever is older)
  • Patient with documented diagnosis of myasthenia gravis (MG) based on medical history and supported by previous evaluations as described in the protocol
  • Documented prior history of positive serologic test or a positive result during screening of anti-acetylcholine receptor (AChR) antibodies or anti-LRP4 antibodies.
  • Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to IVa at screening
  • 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
  • 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).

Key Exclusion Criteria:

  • 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
  • History of thymectomy within 12 months prior to screening or planned during the study
  • 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
  • Myasthenic crisis or Myasthenia Gravis Foundation of America (MGFA) Class V within 1 month of screening
  • No documented meningococcal vaccination within 5 years prior to screening visit unless vaccination will be administered during the screening period and prior to initiation of study treatment
  • Known contraindication to meningococcal vaccines (group ACWY conjugate and group B vaccines) as described in the protocol
  • 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
  • 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
  • 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

235 participants in 4 patient groups

Group 1
Experimental group
Description:
Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP
Treatment:
Drug: Cemdisiran
Other: Placebo
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

Trial contacts and locations

116

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Central trial contact

Clinical Trials Administrator

Data sourced from clinicaltrials.gov

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