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)

Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Monotherapy in Patients With Symptomatic 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)

Study Overview

• Status: Active, not recruiting
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Drug: Pozelimab + Cemdisiran; Drug: Cemdisiran; Other: Placebo; Drug: Pozelimab

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 288
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • Universitair Ziekenhuis Antwerpen
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • AZ Sint-Lucas
• Brazil
  • São Paulo, Brazil, 05403-010
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
  • São Paulo, Brazil, 04038-002
    • Pseg Centro De Pesquisa Clinica S.A
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90110-000
      • IMV Pesquisa Neurológica
  • São Paulo
    • Itapevi, São Paulo, Brazil, 06655-250
      • Jordy Sinapse Medicina LTDA
    • Santo André, São Paulo, Brazil, 09060-870
      • Faculdade de Medicina do ABC
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2X8
      • University of Alberta
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5G2C4
      • Toronto General Hospital
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100032
      • Peking Union Medical College Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangdong, Guangdong, China, 510120
      • Guangdong Hospital of Traditional Chinese Medicine
    • Guangzhou, Guangdong, China, 510120
      • Nanfang Hospital Southern Medical University
    • Shenzhen, Guangdong, China, 518053
      • The University of Hong Kong-Shenzhen Hospital
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510405
      • The First Affiliated Hospital of Guangzhou University of Chinese Medicine
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Renmin Hospital of Wuhan University - Hubei Provincial People's Hospital
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University
  • Jilin
    • Changchun, Jilin, China, 130000
      • The First Hospital of Jilin University
  • Shandong
    • Qingdao, Shandong, China, 266035
      • Qilu Hospital of Shandong University (Qingdan)
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201107
      • Huashan Hospital Fudan University
  • Shanxi
    • Xi’an, Shanxi, China, 710032
      • The Second Affiliated Hospital of the Chinese Peoples' Liberation Army Air Force Medical University
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • Sichuan Provincial People's Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300050
      • Tianjin Medical University General Hospital
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital
  • Copenhagen, Denmark, 2100
    • Rigshospitalet, Copenhagen
  • Odense, Denmark, 05000
    • Odense Universitetshospital
  • North Denmark
    • Aalborg, North Denmark, Denmark, 09000
      • Aalborg Universitetshospital
• France
  • Le Kremlin-Bicêtre, France, 94275
    • CHU Bicêtre
  • Nancy, France, 54035
    • Centre Hospitalier Regional Universitaire (CHRU) de Nancy
  • Paris, France, 75013
    • Hopital de la Pitie Salpetriere
  • Alpes Maritimes
    • Nice, Alpes Maritimes, France, 6002
      • Centre Hospitalier Universitaire de Nice
• Georgia
  • Tbilisi, Georgia, 0186
    • Multiprofile Clinic Consilium Medulla
  • Tbilisi, Georgia, 0114
    • Pineo Medical Ecosystem
  • Tbilisi, Georgia, 0114
    • Ltd New Hospitals
  • Tbilisi, Georgia, 0112
    • Israeli-Georgian Medical Research Clinic Healthycore, LTD
  • Tbilisi, Georgia, 0144
    • LTD National Center of Urology Named after L. Managadze
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Jena, Germany, 07747
    • Universitatsklinikum Jena
  • Bavaria
    • München, Bavaria, Germany, 80336
      • Friedrich Baur Institute
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45127
      • University Hospital Essen
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Universitatsklinikum Munster
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Universitätsklinikum Leipzig
• India
  • Bangalore, India, 560002
    • Bangalore Medical College and Research Institute (BMCRI) - Victoria Hospital
  • Chandigarh, India, 160012
    • Postgraduate Institute of Medical Education & Research
  • Andhra Pradesh
    • Guntur, Andhra Pradesh, India, 522001
      • Government General Hospital, Guntur
  • Gujarat
    • Surat, Gujarat, India, 395001
      • Institute of Neurosciences
  • Hyderabad
    • Panjagutta, Hyderabad, India, 500082
      • Nizam's Institute of Medical Sciences (NIMS)
  • Karnataka
    • Udupi, Karnataka, India, 576104
      • Kasturba Medical College (KMC)
  • Kerala
    • Kochi, Kerala, India, 682041
      • Amrita Institute of Medical Sciences and Research Centre (AIMS)
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Deenanath Mangeshkar Hospital and Research Centre
  • Mumbai
    • Pārel, Mumbai, India, 400012
      • Seth G.S. Medical College & K.E.M. Hospital, Mumbai
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110029
      • All India Institute of Medical Sciences New Delhi
  • Punjab
    • Kochi, Punjab, India, 141008
      • Polakulath Narayanan Renai Medicity Multi Specialty Hospital, Kochi
    • Ludhiana, Punjab, India, 141008
      • Christian Medical College & Hospital
  • Rajasthan
    • Jaipur, Rajasthan, India, 302017
      • Apex Hospital
  • Telangana
    • Hyderabad, Telangana, India, 500034
      • City Neuro Centre, Hyderabad
• Italy
  • Bergamo, Italy, 24127
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Roma, Italy, 00161
    • Universita' Degli Studi di Roma La Sapienza
  • Lazio
    • Rome, Lazio, Italy, 00189
      • Azienda Ospedaliera Sant'Andrea
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta
  • Tuscany
    • Pisa, Tuscany, Italy, 56126
      • Azienda Ospedaliero Universitaria Pisana
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital
  • Hiroshima, Japan, 730-8518
    • Hiroshima City Hiroshima Citiz
  • Osaka, Japan, 543-8555
    • Japanese Red Cross Osaka Hospital
  • Hyōgo
    • Kobe, Hyōgo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
  • Kochi
    • Nankoku, Kochi, Japan, 783-8505
      • Kochi Medical School Hospital
  • Okinawa
    • Ginowan-Shi, Okinawa, Japan, 901-2214
      • Okinawa National Hospital
    • Shimajiri, Okinawa, Japan, 901-1193
      • Okinawa Prefectural Nanbu Medical Center and Children's Medical Center
  • Saitama
    • Kawagoe, Saitama, Japan, 350-8550
      • Saitama Medical University, Saitama Medical Center
  • Tokyo
    • Bunkyo, Tokyo, Japan, 113-8519
      • Medical Hospital of Tokyo Medical and Dental University
    • Shinjuku, Tokyo, Japan, 160-0023
      • Tokyo Medical University Hospital
    • tabashi City, Tokyo, Japan, 173-8610
      • Nihon University Itabashi Hospital
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-8505
      • Yamaguchi University Hospital
• Poland
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 61-731
      • Clinical Research Center Spolka z Ograniczona Odpowiedzialnoscia Medic-R Sp.k
    • Poznan, Greater Poland Voivodeship, Poland, 61-853
      • NZOZ Neuro-Kard
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-505
      • Centrum Neurologii Klinicznej, Krakowska Akademia Neurologii
  • Mazovian
    • Warsaw, Mazovian, Poland, 01-684
      • NeuroProtect
  • Mosavian
    • Warsaw, Mosavian, Poland, 02-097
      • Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-952
      • Gdański Uniwersytet Medyczny
• Serbia
  • Niš, Serbia, 700461
    • University Clinical Centre Nis
• South Korea
  • Daegu, South Korea, 41404
    • Kyungpook National University Chilgok Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
• Spain
  • Barcelona, Spain, 08041
    • Hospital De La Santa Creu I Sant Pau
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
• Taiwan
  • Kaohsiung City, Taiwan, 833
    • Chang Gung Memorial Foundation Kaohsiung Branch
  • Taichung, Taiwan, 40447
    • China Medical University
  • Tainan, Taiwan, 701
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 111
    • Shin Kong Wu Ho Su Memorial Hospital
  • Taoyuan District, Taiwan, 333
    • Chang Gung Memorial Hospital at Linkou
• Turkey (Türkiye)
  • Izmir, Turkey (Türkiye), 35340
    • Dokuz Eylul University Medical Faculty
  • Samsun, Turkey (Türkiye), 55239
    • Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi
  • Trabzon, Turkey (Türkiye), 61080
    • Karadeniz Technical University Farabi Hospital
  • Van
    • Izmit, Van, Turkey (Türkiye), 41380
      • Kocaeli University Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospital Birmingham
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, 511 9NE
      • Sheffield teaching hospital NHS foundation trust
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • HonorHealth Neurology 2018
  • California
    • Irvine, California, United States, 92697
      • University of California Irvine
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Colorado
    • Colorado Springs, Colorado, United States, 80907-5307
      • Colorado Springs Neurological Associates
  • Florida
    • Boca Raton, Florida, United States, 33487
      • SFM Clinical Research, LLC
    • Miami, Florida, United States, 33175
      • Diverse Clinical Research
    • Naples, Florida, United States, 34105
      • Aqualane Clinical Research
    • Orlando, Florida, United States, 32806
      • Neurological Services of Orlando
    • Port Charlotte, Florida, United States, 33952
      • Medsol Clinical Research Center Inc
    • Tampa, Florida, United States, 33612
      • University of South Florida Morsani Center for Advanced Healthcare
  • Illinois
    • Glenview, Illinois, United States, 60026-1301
      • Northshore University Health System
    • O'Fallon, Illinois, United States, 62269
      • St. Elizabeth's Hospital
    • Rolling Meadows, Illinois, United States, 60080
      • Northwest Neurology Ltd. - Clinedge - PPDS
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University School of Medicine
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Dayton Center for Neurological Disorders
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Gardner Neuroscience Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Medicine University City
  • Texas
    • Austin, Texas, United States, 78759
      • National Neuromuscular Research Institute
    • Houston, Texas, United States, 77030
      • Nerve And Muscle Center Of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Male or female participants ≥18 years of age at screening (or ≥ legal age of adulthood based on local regulations, whichever is older)
2. Participant 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-Lipoprotein Receptor-related Protein 4 (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 participant 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 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. 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
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 Human Immunodeficiency Virus (HIV) infection or a positive test at screening per local requirements

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP	Drug: Pozelimab + Cemdisiran; Subcutaneous administration as described in the protocol; Drug: Cemdisiran; SC administration as described in the protocol; Other Names: ALN-CC5; Other: Placebo; SC administration as described in the protocol
Experimental: Group 3; Cemdisiran throughout the study	Drug: Cemdisiran; SC administration as described in the protocol; Other Names: ALN-CC5
Experimental: Group 2; Combination regimen throughout the study. For participants who have not reached week 108 will receive cemdisiran monotherapy in the OLTP.	Drug: Pozelimab + Cemdisiran; Subcutaneous administration as described in the protocol; Drug: Cemdisiran; SC administration as described in the protocol; Other Names: ALN-CC5
Experimental: Group 4; Pozelimab monotherapy in DBTP followed by combination in ETP and OLTP. For participants who have not reached week 108 will receive cemdisiran monotherapy in the OLTP.	Drug: Pozelimab + Cemdisiran; Subcutaneous administration as described in the protocol; Drug: Cemdisiran; SC administration as described in the protocol; Other Names: ALN-CC5; Drug: Pozelimab; SC administration as described in the protocol; Other Names: REGN3918

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score	The total MG-ADL score ranges from 0 to 24 points, with higher scores indicating greater functional impairment and disability	From baseline to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Quantitative Myasthenia Gravis (QMG) score	QMG total scores range from 0 to 39, with higher scores representing greater impairment	Week 24
Change from baseline in the Myasthenia Gravis Composite (MGC) total score	MGC score ranges from 0 to 50, with higher score indicating higher impairment	Week 24
Concentrations of total pozelimab in serum		Through study duration, approximate 172 weeks
Concentrations of cemdisiran and its metabolites in plasma		Through study duration, approximate 172 weeks
Incidence of treatment-emergent ADAs to cemdisiran over time		Through study duration, approximate 172 weeks
Percent change in CH50 over time		Through study duration, approximately 172 weeks
Change in total complement hemolysis activity assay (CH50) over time		Through study duration, approximately 172 weeks
Achievement of a ≥3-point reduction (improvement) in MG-ADL total score		From baseline to week 24
Achievement of a ≥5-point reduction (improvement) in QMG total score		From baseline to week 24
Achievement of a ≥2-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-point reduction on MG-ADL total score		From baseline to week 24
Achievement of a ≥3-, 4-, 6-, 7-, 8-, 9-, or 10-point reduction on QMG		From baseline to week 24
Achievement of a consistent response on the MG-ADL	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	From baseline to week 24
Achievement of Minimal Symptom Expression (MSE)	Score of 0 to 1 on the MG-ADL	Week 24
Change from baseline in Myasthenia Gravis Quality of Life (MG-QOL15r) total score	Total score ranges from 0 to 30 points; a higher score represents greater impairment	Week 24
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) in participants treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo		Through week 24
Incidence and severity of Serious Adverse Events (SAEs) in participants treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo		Through week 24
Incidence and severity of Adverse Events of Special Interest (AESIs) in participants treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo		Through week 24
Concentrations of total Complement component 5 (C5) in plasma		Through study duration, approximate 172 weeks
Incidence of treatment-emergent Anti-Drug Antibodies (ADAs) to pozelimab over time		Through study duration, approximately 172 weeks

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• Study Informational Website

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2021
• Primary Completion (Actual): July 8, 2025
• Study Completion (Estimated): November 11, 2028

Study Registration Dates

• First Submitted: September 27, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (Actual): October 7, 2021

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis
• Other Study ID Numbers: R3918-MG-2018; 2020-003272-41 (EudraCT Number); 2023-508842-17-00 (Ctis: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry),
• the legal authority to share the data, and
• ensured the ability to protect participant privacy.

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No