Clinical trial 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
Official title: Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Monotherapy in Patients With Symptomatic Generalized Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Generalized Myasthenia Gravis
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-10-07
Enrollment: 335
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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)

Detailed 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)

Eligibility 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

Primary outcomes:
measure: Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score
timeFrame: From baseline to week 24
Secondary outcomes:
measure: Change from baseline in Quantitative Myasthenia Gravis (QMG) score
timeFrame: Week 24
measure: Achievement of a ≥3-point reduction (improvement) in MG-ADL total score
timeFrame: From baseline to week 24
measure: Achievement of a ≥5-point reduction (improvement) in QMG total score
timeFrame: From baseline to week 24
measure: Achievement of a consistent response on the MG-ADL
timeFrame: From baseline to week 24
measure: Achievement of minimal symptom expression (MSE)
timeFrame: Week 24
measure: Change from baseline in the Myasthenia Gravis Composite (MGC) total score
timeFrame: Week 24
measure: Change from baseline in Myasthenia Gravis Quality of Life (MG QOL15r) total score
timeFrame: Week 24
measure: Achievement of a ≥2-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-point reduction on MG-ADL total score
timeFrame: From baseline to week 24
measure: Achievement of a ≥3-, 4-, 6-, 7-, 8-, 9-, or 10-point reduction on QMG
timeFrame: From baseline to week 24
measure: Incidence and severity of treatment-related adverse events (TEAEs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo
timeFrame: Through week 24
measure: Incidence and severity of serious adverse events (SAEs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo
timeFrame: Through week 24
measure: Incidence and severity of adverse events of special interest (AESIs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo
timeFrame: Through week 24
measure: Concentrations of total pozelimab in serum
timeFrame: Through study duration, approximate 172 weeks
measure: Concentrations of total complement component 5 (C5) in plasma
timeFrame: Through study duration, approximate 172 weeks
measure: Concentrations of cemdisiran and its metabolites in plasma
timeFrame: Through study duration, approximate 172 weeks
measure: Incidence of treatment-emergent anti-drug antibodies (ADAs) to pozelimab over time
timeFrame: Through study duration, approximately 172 weeks
measure: Incidence of treatment-emergent ADAs to cemdisiran over time
timeFrame: Through study duration, approximate 172 weeks
measure: Change in total complement hemolysis activity assay (CH50) over time
timeFrame: Through study duration, approximately 172 weeks
measure: Percent change in CH50 over time
timeFrame: Through study duration, approximately 172 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Neurology 2018
state: Arizona
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Colorado Springs
country: United States
facility: Colorado Springs Neurological Associates
state: Colorado
city: Boca Raton
country: United States
facility: SFM Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: Diverse Clinical Research
state: Florida
city: Naples
country: United States
facility: Aqualane Clinical Research
state: Florida
city: Orlando
country: United States
facility: Neurological Services of Orlando
state: Florida
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center Inc
state: Florida
city: Tampa
country: United States
facility: University of South Florida Morsani Center for Advanced Healthcare
state: Florida
city: Chicago
country: United States
facility: Northwestern University - Parkinson's Disease and Movement Disorders Center
state: Illinois
city: Glenview
country: United States
facility: NorthShore University Health System
state: Illinois
city: O'Fallon
country: United States
facility: St. Elizabeth's Hospital
state: Illinois
city: Rolling Meadows
country: United States
facility: Northwest Neurology Ltd. - Clinedge - PPDS
state: Illinois
city: Detroit
country: United States
facility: Wayne State University School of Medicine
state: Michigan
city: New York
country: United States
facility: Weill Cornell Medicine - Peripheral Neuropathy Center
state: New York
city: Charlotte
country: United States
facility: Atrium Health Neurosciences Institute
state: North Carolina
city: Centerville
country: United States
facility: Dayton Center for Neurological Disorders
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Gardner Neuroscience Institute
state: Ohio
city: Philadelphia
country: United States
facility: Penn Medicine University City
state: Pennsylvania
city: Arlington
country: United States
facility: Texas Institute for Neurological Disorders - Arlington
state: Texas
city: Austin
country: United States
facility: National Neuromuscular Research Institute
state: Texas
city: Houston
country: United States
facility: Nerve and Muscle Center of Texas
state: Texas
city: Sydney
country: Australia
facility: Southern Neurology
state: New South Wales
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Victoria
city: Nedlands
country: Australia
facility: Perron Institute for Neurological and Translational Science
state: Western Australia
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
state: Antwerp
city: Lodelinsart
country: Belgium
facility: Chu Charleroi
state: Hainaut
city: Gent
country: Belgium
facility: AZ Sint-Lucas
state: Oost-Vlaanderen
city: Bruxelles
country: Belgium
facility: Hospital Erasme
city: Porto Alegre
country: Brazil
facility: IMV Pesquisa Neurologica
state: Rio Grande Do Sul
city: Itapevi
country: Brazil
facility: Jordy Sinapse Medicina LTDA
state: Sao Paulo
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina Do ABC
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Pseg Centro de Pesquisa Clinica S.A
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre hospitalier de l'Universite de Montreal
state: Quebec
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangdong
country: China
facility: Guangdong Hospital of Traditional Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: The University of Hong Kong-Shenzhen Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou University of Chinese Medicine
state: Guangzhou
city: Haikou City
country: China
facility: Hainan General Hospital
state: Hainan
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University - Hubei Provincial People's Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Qingdao
country: China
facility: Qilu Hospital of Shandong University (Qingdan)
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital Fudan University
state: Shanghai
city: Xi'an
country: China
facility: The Second Affiliated Hospital of the Chinese Peoples' Liberation Army Air Force Medical University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno
state: Jihomoravsky Kraj
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
state: Moravskoslezsky Kraj
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
state: Nordjylland
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Copenhagen
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice
state: Alpes Maritimes
city: Le Kremlin-Bicetre
country: France
facility: CHU Bicetre
city: Nancy
country: France
facility: Centre Hospitalier Regional Universitaire (CHRU) de Nancy
city: Paris
country: France
facility: Hopital de la Pitie Salpetriere
city: Tbilisi
country: Georgia
facility: Israeli-Georgian Medical Research Clinic Healthycore, LTD
city: Tbilisi
country: Georgia
facility: LTD New Hospitals
city: Tbilisi
country: Georgia
facility: Pineo Medical Ecosystem
city: Tbilisi
country: Georgia
facility: LTD National Center of Urology Named after L. Managadze
city: Tbilisi
country: Georgia
facility: Multiprofile Clinic Consilium Medulla
city: Munchen
country: Germany
facility: Friedrich Baur Institute
state: Bayern
city: Munster
country: Germany
facility: Universitatsklinikum Munster
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: University Hospital Essen
state: North Rhine-Westphalia
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
state: Sachsen
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin Berlin
city: Jena
country: Germany
facility: Universitatsklinikum Jena
city: Guntur
country: India
facility: Government General Hospital, Guntur
state: Andhra Pradesh
city: New Delhi
country: India
facility: All India Institute of Medical Sciences New Delhi
state: Delhi
city: Surat
country: India
facility: Institute of Neurosciences
state: Gujarat
city: Panjagutta
country: India
facility: Nizam's Institute of Medical Sciences (NIMS)
state: Hyderabad
city: Udupi
country: India
facility: Kasturba Medical College (KMC)
state: Karnataka
city: Kochi
country: India
facility: Amrita Institute of Medical Sciences and Research Centre (AIMS)
state: Kerala
city: Thrissur
country: India
facility: Jubilee Mission Hospital
state: Kerala
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital and Research Centre
state: Maharashtra
city: Parel
country: India
facility: Seth G.S. Medical College & K.E.M. Hospital, Mumbai
state: Mumbai
city: Kochi
country: India
facility: Polakulath Narayanan Renai Medicity Multi Specialty Hospital, Kochi
state: Punjab
city: Ludhiana
country: India
facility: Christian Medical College & Hospital
state: Punjab
city: Jaipur
country: India
facility: Apex Hospital
state: Rajasthan
city: Hyderabad
country: India
facility: City Neuro Centre, Hyderabad
state: Telangana
city: Lucknow
country: India
facility: Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) - Department of Neurology
state: Uttar Pradesh
city: Bangalore
country: India
facility: Bangalore Medical College and Research Institute (BMCRI) - Victoria Hospital
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education & Research
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'andrea
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta
state: Lombardia
city: Pavia
country: Italy
facility: IRCCS Mondino Foundation
state: Lombardy
city: Naples
country: Italy
facility: AORN Cardarelli Napoli
state: Napoli
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Roma
country: Italy
facility: Universita' Degli Studi di Roma La Sapienza
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Nankoku
country: Japan
facility: Kochi Medical School Hospital
state: Koti
city: Ginowan-Shi
country: Japan
facility: Okinawa National Hospital
state: Okinawa
city: Shimajiri
country: Japan
facility: Okinawa Prefectural Nanbu Medical Center and Children's Medical Center
state: Okinawa
city: Kawagoe
country: Japan
facility: Saitama Medical University, Saitama Medical Center
state: Saitama
city: Kodaira
country: Japan
facility: Showa General Hospital
state: Tokoyo
city: Bunkyo-ku
country: Japan
facility: Medical Hospital of Tokyo Medical and Dental University
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Nihon University Itabashi Hospital
state: Tokyo
city: Shinjuku
country: Japan
facility: Tokyo Medical University Hospital
state: Tokyo
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citiz
city: Osaka
country: Japan
facility: Japanese Red Cross Osaka Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Krakow
country: Poland
facility: Centrum Neurologii Klinicznej, Krakowska Akademia Neurologii
state: Malopolskie
city: Warsaw
country: Poland
facility: NeuroProtect
state: Mazovian
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny
state: Mosavian
city: Gdansk
country: Poland
facility: Gdanski Uniwersytet Medyczny
state: Pomorskie
city: Poznan
country: Poland
facility: Clinical Research Center Spolka z Ograniczona Odpowiedzialnoscia Medic-R Sp.k
state: Wielkopolskie
city: Poznan
country: Poland
facility: NZOZ Neuro-kard
state: Wielkopolskie
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Nis
country: Serbia
facility: University Clinical Centre Nis
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Memorial Foundation Kaohsiung Branch
city: Taichung
country: Taiwan
facility: China Medical University
city: Tainan City
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Shin Kong Wu Ho Su Memorial Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital at Linkou
city: Izmit
country: Turkey
facility: Kocaeli University Hospital
state: Van
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medical Faculty
city: Samsun
country: Turkey
facility: Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi
city: Trabzon
country: Turkey
facility: Karadeniz Technical University Farabi Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospital NHS Foundation Trust
state: South Yorkshire
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: