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NCT Number: NCT05070858

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

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 of the 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)

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Universitair Ziekenhuis Antwerpen, Edegem, Antwerp, Belgium

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About this study

DBTP- Double Blind Treatment Period (24 weeks) ETP - Extension Treatment Period (28 weeks) OLTP- Open Label Treatment Period (68 weeks) FUP-Off treatment Follow Up Period (52 weeks)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Male or female participants ≥18 years of age at screening (or ≥ legal age of adulthood based on local regulations, whichever is older)
  • Participant 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-Lipoprotein Receptor-related Protein 4 (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 as described in the protocol
  • Currently receiving an acetylcholinesterase inhibitor or documented reason for not using acetylcholinesterase inhibitor therapy per investigator
  • Currently receiving an Immunosuppressive Therapy (IST) for MG, or documented reason why the participant is not taking an IST per investigator
  • If currently receiving an IST, not anticipated to have IST dosage changed before randomization or during Double-Blind Treatment Period (DBTP).
  • 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:

  • 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 MGFA Class V within 1 month of screening
  • 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
  • Known contraindication to meningococcal vaccines (group ACWY conjugate and group B vaccines) as described in the protocol
  • Participants 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 Human Immunodeficiency Virus (HIV) infection or a positive test at screening per local requirements

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Treatment and study plan

Pozelimab + Cemdisiran

Drug

Subcutaneous administration as described in the protocol

Cemdisiran

Drug

SC administration as described in the protocol

Other names: ALN-CC5

Placebo

Other

SC administration as described in the protocol

Pozelimab

Drug

SC administration as described in the protocol

Other names: REGN3918

Primary outcomes

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

    Time frame: From baseline to week 24

    The total MG-ADL score ranges from 0 to 24 points, with higher scores indicating greater functional impairment and disability

Secondary outcomes

  1. Change from baseline in Quantitative Myasthenia Gravis (QMG) score

    Time frame: Week 24

    QMG total scores range from 0 to 39, with higher scores representing greater impairment

  2. Achievement of a ≥3-point reduction (improvement) in MG-ADL total score

    Time frame: From baseline to week 24

  3. Achievement of a ≥5-point reduction (improvement) in QMG total score

    Time frame: From baseline to week 24

  4. Achievement of a consistent response on the MG-ADL

    Time frame: From baseline to week 24

    A participant with a ≥2-point reduction (improvement) in MG-ADL total score on 2 or more consecutive assessments spanning 4 or more weeks during the DBTP

  5. Achievement of Minimal Symptom Expression (MSE)

    Time frame: Week 24

    Score of 0 to 1 on the MG-ADL

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

    Time frame: Week 24

    MGC score ranges from 0 to 50, with higher score indicating higher impairment

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

    Time frame: Week 24

    Total score ranges from 0 to 30 points; a higher score represents greater impairment

  8. Achievement of a ≥2-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-point reduction on MG-ADL total score

    Time frame: From baseline to week 24

  9. Achievement of a ≥3-, 4-, 6-, 7-, 8-, 9-, or 10-point reduction on QMG

    Time frame: From baseline to week 24

  10. Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) in participants treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo

    Time frame: Through week 24

  11. Incidence and severity of Serious Adverse Events (SAEs) in participants treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo

    Time frame: Through week 24

  12. Incidence and severity of Adverse Events of Special Interest (AESIs) in participants treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo

    Time frame: Through week 24

  13. Concentrations of total pozelimab in serum

    Time frame: Through study duration, approximate 172 weeks

  14. Concentrations of total Complement component 5 (C5) in plasma

    Time frame: Through study duration, approximate 172 weeks

  15. Concentrations of cemdisiran and its metabolites in plasma

    Time frame: Through study duration, approximate 172 weeks

  16. Incidence of treatment-emergent Anti-Drug Antibodies (ADAs) to pozelimab over time

    Time frame: Through study duration, approximately 172 weeks

  17. Incidence of treatment-emergent ADAs to cemdisiran over time

    Time frame: Through study duration, approximate 172 weeks

  18. Change in total complement hemolysis activity assay (CH50) over time

    Time frame: Through study duration, approximately 172 weeks

  19. Percent change in CH50 over time

    Time frame: Through study duration, approximately 172 weeks

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study title

Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Monotherapy in Patients With Symptomatic Generalized Myasthenia Gravis

Acronym: NIMBLE

Important dates

Study start
2021
Primary completion
2025
Study completion
2028
First posted
Oct 7, 2021
Registry last updated
Jul 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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