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

NCT05070858 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: R3918-MG-20182020-003272-412023-508842-17-00
• Study Type: interventional
• Target: 288
• Locations: 19 countries
• Sites: 116

Brief Summary

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)

Conditions

Generalized Myasthenia Gravis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (19)

• Change from baseline in Quantitative Myasthenia Gravis (QMG) score

  Week 24

• 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 consistent response on the MG-ADL

  From baseline to week 24

• Achievement of Minimal Symptom Expression (MSE)

  Week 24

Study Arms (4)

Group 1

EXPERIMENTAL

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

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

Group 2

EXPERIMENTAL

Combination regimen throughout the study. For participants who have not reached week 108 will receive cemdisiran monotherapy in the OLTP.

Drug: Pozelimab + Cemdisiran; Drug: Cemdisiran

Group 3

EXPERIMENTAL

Cemdisiran throughout the study

Drug: Cemdisiran

Group 4

EXPERIMENTAL

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; Drug: Cemdisiran; Drug: Pozelimab

Interventions

Cemdisiran DRUG

SC administration as described in the protocol

Also known as: ALN-CC5

Group 1; Group 2; Group 3; Group 4

Placebo OTHER

SC administration as described in the protocol

Group 1

Pozelimab DRUG

SC administration as described in the protocol

Also known as: REGN3918

Group 4

Pozelimab + Cemdisiran DRUG

Subcutaneous administration as described in the protocol

Group 1; Group 2; Group 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (116)

HonorHealth Neurology 2018

Scottsdale, Arizona, 85251, United States

Location

University of California Irvine

Irvine, California, 92697, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Colorado Springs Neurological Associates

Colorado Springs, Colorado, 80907-5307, United States

Location

SFM Clinical Research, LLC

Boca Raton, Florida, 33487, United States

Location

Diverse Clinical Research

Miami, Florida, 33175, United States

Location

Aqualane Clinical Research

Naples, Florida, 34105, United States

Location

Neurological Services of Orlando

Orlando, Florida, 32806, United States

Location

Medsol Clinical Research Center Inc

Port Charlotte, Florida, 33952, United States

Location

University of South Florida Morsani Center for Advanced Healthcare

Tampa, Florida, 33612, United States

Location

NorthShore University Health System

Glenview, Illinois, 60026-1301, United States

Location

St. Elizabeth's Hospital

O'Fallon, Illinois, 62269, United States

Location

Northwest Neurology Ltd. - Clinedge - PPDS

Rolling Meadows, Illinois, 60080, United States

Location

Wayne State University School of Medicine

Detroit, Michigan, 48201, United States

Location

Dayton Center for Neurological Disorders

Centerville, Ohio, 45459, United States

Location

University of Cincinnati Gardner Neuroscience Institute

Cincinnati, Ohio, 45219, United States

Location

Penn Medicine University City

Philadelphia, Pennsylvania, 19104, United States

Location

National Neuromuscular Research Institute

Austin, Texas, 78759, United States

Location

Nerve and Muscle Center of Texas

Houston, Texas, 77030, United States

Location

Universitair Ziekenhuis Antwerpen

Edegem, Antwerp, 2650, Belgium

Location

AZ Sint-Lucas

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

IMV Pesquisa Neurologica

Porto Alegre, Rio Grande do Sul, 90110-000, Brazil

Location

Jordy Sinapse Medicina LTDA

Itapevi, São Paulo, 06655-250, Brazil

Location

Faculdade de Medicina Do ABC

Santo André, São Paulo, 09060-870, Brazil

Location

Pseg Centro de Pesquisa Clinica S.A

São Paulo, 04038-002, Brazil

Location

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo

São Paulo, 05403-010, Brazil

Location

University of Alberta

Edmonton, Alberta, T6G 2X8, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G2C4, Canada

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

Guangdong Hospital of Traditional Chinese Medicine

Guangdong, Guangdong, 510120, China

Location

Nanfang Hospital Southern Medical University

Guangzhou, Guangdong, 510120, China

Location

The University of Hong Kong-Shenzhen Hospital

Shenzhen, Guangdong, 518053, China

Location

The First Affiliated Hospital of Guangzhou University of Chinese Medicine

Guangzhou, Guangzhou, 510405, China

Location

Hainan General Hospital

Haikou, Hainan, 570311, China

Location

Renmin Hospital of Wuhan University - Hubei Provincial People's Hospital

Wuhan, Hubei, 430060, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130000, China

Location

Qilu Hospital of Shandong University (Qingdan)

Qingdao, Shandong, 266035, China

Location

Huashan Hospital Fudan University

Shanghai, Shanghai Municipality, 201107, China

Location

The Second Affiliated Hospital of the Chinese Peoples' Liberation Army Air Force Medical University

Xi’an, Shanxi, 710032, China

Location

Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610072, China

Location

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300050, China

Location

Aalborg Universitetshospital

Aalborg, North Denmark, 09000, Denmark

Location

Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Rigshospitalet, Copenhagen

Copenhagen, 2100, Denmark

Location

Odense Universitetshospital

Odense, 05000, Denmark

Location

Centre Hospitalier Universitaire de Nice

Nice, Alpes Maritimes, 6002, France

Location

CHU Bicetre

Le Kremlin-Bicêtre, 94275, France

Location

Centre Hospitalier Regional Universitaire (CHRU) de Nancy

Nancy, 54035, France

Location

Hopital de la Pitie Salpetriere

Paris, 75013, France

Location

Israeli-Georgian Medical Research Clinic Healthycore, LTD

Tbilisi, 0112, Georgia

Location

LTD New Hospitals

Tbilisi, 0114, Georgia

Location

Pineo Medical Ecosystem

Tbilisi, 0114, Georgia

Location

LTD National Center of Urology Named after L. Managadze

Tbilisi, 0144, Georgia

Location

Multiprofile Clinic Consilium Medulla

Tbilisi, 0186, Georgia

Location

Friedrich Baur Institute

München, Bavaria, 80336, Germany

Location

University Hospital Essen

Essen, North Rhine-Westphalia, 45127, Germany

Location

Universitatsklinikum Munster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Universitatsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

Location

Charite - Universitatsmedizin Berlin

Berlin, 10117, Germany

Location

Universitatsklinikum Jena

Jena, 07747, Germany

Location

Government General Hospital, Guntur

Guntur, Andhra Pradesh, 522001, India

Location

Institute of Neurosciences

Surat, Gujarat, 395001, India

Location

Nizam's Institute of Medical Sciences (NIMS)

Panjagutta, Hyderabad, 500082, India

Location

Kasturba Medical College (KMC)

Udupi, Karnataka, 576104, India

Location

Amrita Institute of Medical Sciences and Research Centre (AIMS)

Kochi, Kerala, 682041, India

Location

Deenanath Mangeshkar Hospital and Research Centre

Pune, Maharashtra, 411004, India

Location

Seth G.S. Medical College & K.E.M. Hospital, Mumbai

Pārel, Mumbai, 400012, India

Location

All India Institute of Medical Sciences New Delhi

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Polakulath Narayanan Renai Medicity Multi Specialty Hospital, Kochi

Kochi, Punjab, 141008, India

Location

Christian Medical College & Hospital

Ludhiana, Punjab, 141008, India

Location

Apex Hospital

Jaipur, Rajasthan, 302017, India

Location

City Neuro Centre, Hyderabad

Hyderabad, Telangana, 500034, India

Location

Bangalore Medical College and Research Institute (BMCRI) - Victoria Hospital

Bangalore, 560002, India

Location

Postgraduate Institute of Medical Education & Research

Chandigarh, 160012, India

Location

Azienda Ospedaliera Sant'andrea

Rome, Lazio, 00189, Italy

Location

Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta

Milan, Lombardy, 20133, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, 56126, Italy

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Universita' Degli Studi di Roma La Sapienza

Roma, 00161, Italy

Location

Kobe City Medical Center General Hospital

Kobe, Hyōgo, 650-0047, Japan

Location

Kochi Medical School Hospital

Nankoku, Kochi, 783-8505, Japan

Location

Okinawa National Hospital

Ginowan-Shi, Okinawa, 901-2214, Japan

Location

Okinawa Prefectural Nanbu Medical Center and Children's Medical Center

Shimajiri, Okinawa, 901-1193, Japan

Location

Saitama Medical University, Saitama Medical Center

Kawagoe, Saitama, 350-8550, Japan

Location

Medical Hospital of Tokyo Medical and Dental University

Bunkyo, Tokyo, 113-8519, Japan

Location

Tokyo Medical University Hospital

Shinjuku, Tokyo, 160-0023, Japan

Location

Nihon University Itabashi Hospital

tabashi City, Tokyo, 173-8610, Japan

Location

Yamaguchi University Hospital

Ube, Yamaguchi, 755-8505, Japan

Location

Chiba University Hospital

Chiba, 260-8677, Japan

Location

Hiroshima City Hiroshima Citiz

Hiroshima, 730-8518, Japan

Location

Japanese Red Cross Osaka Hospital

Osaka, 543-8555, Japan

Location

Clinical Research Center Spolka z Ograniczona Odpowiedzialnoscia Medic-R Sp.k

Poznan, Greater Poland Voivodeship, 61-731, Poland

Location

NZOZ Neuro-kard

Poznan, Greater Poland Voivodeship, 61-853, Poland

Location

Centrum Neurologii Klinicznej, Krakowska Akademia Neurologii

Krakow, Lesser Poland Voivodeship, 31-505, Poland

Location

NeuroProtect

Warsaw, Mazovian, 01-684, Poland

Location

Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny

Warsaw, Mosavian, 02-097, Poland

Location

Gdanski Uniwersytet Medyczny

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

University Clinical Centre Nis

Niš, 700461, Serbia

Location

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Chang Gung Memorial Foundation Kaohsiung Branch

Kaohsiung City, 833, Taiwan

Location

China Medical University

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 701, Taiwan

Location

Shin Kong Wu Ho Su Memorial Hospital

Taipei, 111, Taiwan

Location

Chang Gung Memorial Hospital at Linkou

Taoyuan District, 333, Taiwan

Location

Kocaeli University Hospital

Izmit, Van, 41380, Turkey (Türkiye)

Location

Dokuz Eylul University Medical Faculty

Izmir, 35340, Turkey (Türkiye)

Location

Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi

Samsun, 55239, Turkey (Türkiye)

Location

Karadeniz Technical University Farabi Hospital

Trabzon, 61080, Turkey (Türkiye)

Location

Sheffield Teaching Hospital NHS Foundation Trust

Sheffield, South Yorkshire, 511 9NE, United Kingdom

Location

University Hospital Birmingham

Birmingham, B15 2TH, United Kingdom

Location

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: October 7, 2021
• Study Start: December 14, 2021
• Primary Completion: July 8, 2025
• Study Completion (Estimated): November 11, 2028
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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

Locations

BR (5); US (19); DK (4); FR (4); PL (6); JP (12); GE (5); DE (6); ES (2); IN (14); IT (5); GB (2); TW (5); TU (4); CN (15); BE (2); SE (1); CA (3); KR (2)