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

Generalized Myasthenia Gravis Clinical Trial

— NIMBLE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05070858
• Other study ID #: R3918-MG-2018
• Secondary ID: 2020-003272-41
• Status: Recruiting
• Phase: Phase 3
• Start date: December 14, 2021
• Est. completion date: March 23, 2028

Study information

• Verified date: March 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 235
• Est. completion date: March 23, 2028
• Est. primary completion date: August 29, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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).

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. 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

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

Related Conditions & MeSH terms

• Generalized Myasthenia Gravis
• Muscle Weakness
• Myasthenia Gravis

Intervention

Drug:
• Pozelimab + Cemdisiran
Subcutaneous administration as described in the protocol
• Cemdisiran
SC administration as described in the protocol

Other:
• Placebo
SC administration as described in the protocol

Drug:
• Pozelimab
SC administration as described in the protocol

Locations

Country	Name	City	State
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	St. Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Perron Institute for Neurological and Translational Science	Nedlands	Western Australia
Australia	Southern Neurology	Sydney	New South Wales
Belgium	Hospital Erasme	Bruxelles
Belgium	Universitair Ziekenhuis Antwerpen	Edegem	Antwerp
Belgium	AZ Sint-Lucas	Gent	Oost-Vlaanderen
Belgium	Chu Charleroi	Lodelinsart	Hainaut
Brazil	Jordy Sinapse medicina LTDA	Itapevi	Sao Paulo
Brazil	Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo	Sao Paulo
Canada	University of Alberta	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
Czechia	Fakultni Nemocnice Brno	Brno	Jihomoravsky Kraj
Czechia	Fakultni nemocnice Ostrava	Ostrava	Moravskoslezsky Kraj
Denmark	Aalborg Universitetshospital - Sygehusapoteket	Aalborg	Nordjylland
Denmark	Aarhus University Hospital	Aarhus N
Denmark	Copenhagen Neuromuscular Clinic at Rigshospitalet	Copenhagen
Denmark	Odense Universitetshospital - Infektionsmedicinsk Afdeling	Odense
France	CHU Bicetre	Le Kremlin-Bicetre
France	Centre Hospitalier Regional Universitaire (CHRU) de Nancy	Nancy
France	Centre Hospitalier Universitaire (CHU) de Nice	Nice	Alpes-Maritimes
France	Hopital de la Pitie Salpetriere	Paris
Georgia	LTD "Israeli-Georgian Medical Research Clinic HEALTHYCORE"	Tbilisi
Georgia	LTD National Center of Urology Named after L. Managadze	Tbilisi
Georgia	LTD New Hospitals	Tbilisi
Georgia	Multiprofile Clinic Consilium Medulla	Tbilisi
Georgia	Pineo Medical Ecosystem	Tbilisi
Germany	Charite - Universitatsmedizin Berlin	Berlin
Germany	University Hospital Essen, Dep. of Neurology	Essen	NRW
Germany	Universitatsklinikum Jena	Jena
Germany	Universitatsklinikum Leipzig	Leipzig	Sachsen
Germany	Friedrich-Baur-Institute Dep. of Neurology Klinikum Munchen	Munchen	Bayern
Germany	Universitatsklinikum Munster	Munster	Nordrhein-Westfalen
India	Bangalore Medical College and Research Institute (BMCRI) - Victoria Hospital	Bangalore
India	Postgraduate Institute of Medical Education & Research	Chandigarh
India	Government General Hospital, Guntur	Guntur	Andhra Pradesh
India	City Neuro Centre, Hyderabad	Hyderabad	Telangana
India	Apex Hospital	Jaipur	Rajasthan
India	Amrita Institute of Medical Sciences and Research Centre (AIMS)	Kochi	Kerala
India	Polakulath Narayanan Renai Medicity Multi Specialty Hospital, Kochi	Kochi	Punjab
India	Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) - Department of Neurology	Lucknow	Uttar Pradesh
India	Department of Neurology, Christian Medical College & Hospital	Ludhiana	Punjab
India	Kasturba Medical College (KMC) - Udupi	Manipal	Karnataka
India	All India Institute of Medical Sciences New Delhi	New Delhi	Delhi
India	Nizam's Institute of Medical Sciences (NIMS)	Panjagutta	Hyderabad
India	Seth G.S. Medical College & K.E.M. Hospital, Mumbai	Parel	Mumbai
India	Deenanath Mangeshkar Hospital and Research Centre	Pune	Maharashtra
India	Institute of NeuroSciences	Surat	Gujarat
India	Jubilee Mission Hospital	Thrissur	Kerala
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta	Milano	Lombardia
Italy	AORN Cardarelli Napoli	Naples	Napoli
Italy	IRCCS Mondino Foundation	Pavia	Lombardia
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana
Italy	Azienda Ospedaliera Sant'andrea	Roma	Lazio
Italy	Universita' Degli Studi di Roma La Sapienza	Roma
Japan	Medical Hospital of Tokyo Medical and Dental University	Bunkyo-ku	Tokyo
Japan	Chiba University Hospital	Chiba
Japan	Okinawa National Hospital	Ginowan-Shi	Okinawa
Japan	Hiroshima City Hiroshima Citiz	Hiroshima
Japan	Nihon University Itabashi Hospital	Itabashi-ku	Tokyo
Japan	Saitama Medical University, Saitama Medical Center	Kawagoe	Saitama
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	Showa General Hospital	Kodaira	Tokoyo
Japan	Kochi Medical School Hospital	Nankoku-shi	Koti
Japan	Japanese Red Cross Osaka Hospital	Osaka
Japan	Okinawa Prefectural Nanbu Medical Center and Children's Medical Center	Shimajiri-Gun	Okinawa
Japan	Tokyo Medical University Hospital	Shinjuku ku	Tokyo
Japan	Yamaguchi University Hospital	UBE	Yamaguchi
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu	North Gyeongsang
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi
Poland	Gdanski Uniwersytet Medyczny	Gdansk	Pomorskie
Poland	Centrum Neurologii Klinicznej, Krakowska Akademia Neurologii	Krakow	Malopolskie
Poland	Clinical Research Center Spolka z ograniczona odpowiedzialnoscia Medic-R Sp.k	Poznan	Wielkopolskie
Poland	NZOZ Neuro-kard	Poznan	Wielkopolskie
Poland	Neuroprotect	Warsaw	Mazovian
Poland	Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny	Warszawa	Mazowieckie
Serbia	University Clinical Center of Serbia - PPDS	Belgrade
Serbia	University Clinical Centre Nis	Nis
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario La Paz - PPDS	Madrid
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Taiwan	Chang Gung Memorial Foundation, Kaohsiung Branch	Kaohsiung City
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan City
Taiwan	Shin Kong Wu Ho Su Memorial Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital at Linkou	Taoyuan
Turkey	Dokuz Eylul University Medical Faculty	Izmir
Turkey	Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi	Samsun
Turkey	Karadeniz Technical University Farabi Hospital	Trabzon
Turkey	Kocaeli University Hospital	Umuttepe	Van
United Kingdom	University Hospital Birmingham	Birmingham
United Kingdom	Sheffield Teaching Hospital NHS Foundation Trust	Sheffield	South Yorkshire
United States	Texas Institute for Neurological Disorders - Arlington	Arlington	Texas
United States	National Neuromuscular Research Institute	Austin	Texas
United States	SFM Clinical Research, LLC	Boca Raton	Florida
United States	Dayton Center for Neurological Disorders	Centerville	Ohio
United States	Atrium Health Neurosciences Institute Charlotte, a facility of Carolinas Medical Center	Charlotte	North Carolina
United States	Northwestern University - Clinical Study Location - Parkinson's Disease and Movement Disorders Center	Chicago	Illinois
United States	University of Cincinnati Gardner Neuroscience Institute	Cincinnati	Ohio
United States	Colorado Springs Neurological Associates	Colorado Springs	Colorado
United States	Wayne State University School of Medicine	Detroit	Michigan
United States	NorthShore University Health System	Glenview	Illinois
United States	Nerve and Muscle Center of Texas	Houston	Texas
United States	University of Southern California	Los Angeles	California
United States	Diverse Clinical Research	Miami	Florida
United States	Aqualane Clinical Research	Naples	Florida
United States	Weill Cornell Medicine - Peripheral Neuropathy Center	New York	New York
United States	St. Elizabeth's Hospital	O'Fallon	Illinois
United States	University of California, Irvine	Orange	California
United States	Neurological Services of Orlando	Orlando	Florida
United States	Penn Medicine University City	Philadelphia	Pennsylvania
United States	HonorHealth Neurology	Phoenix	Arizona
United States	Medsol Clinical Research Center Inc	Port Charlotte	Florida
United States	Northwest Neurology Ltd., Clinical Research Dept	Rolling Meadows	Illinois
United States	University of South Florida Morsani Center for Advanced Healthcare	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  France,  Georgia,  Germany,  India,  Italy,  Japan,  Korea, Republic of,  Poland,  Serbia,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Proportion of patients responding on the MG-ADL	=3-point improvement	From baseline to week 24
Secondary	Proportion of patients responding on the QMG	=5-point improvement	From baseline to week 24
Secondary	Proportion of patients with consistent response on the MG-ADL	At least a 2-point MG-ADL improvement on 2 or more consecutive assessments spanning 4 or more weeks during the DBTP	From baseline to week 24
Secondary	Proportion of patients with minimal symptom expression (MSE)	Score of 0 to 1 on the MG-ADL	Week 24
Secondary	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
Secondary	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
Secondary	Proportion of patients with improvement point thresholds on MG-ADL	=2, 4, 5, 6, 7, 8, 9, or 10	From baseline to week 24
Secondary	Proportion of patients with improvement point thresholds on QMG	=3, 4, 6, 7, 8, 9, or 10	From baseline to week 24
Secondary	Incidence and severity of treatment-related adverse events (TEAEs) in patients treated with pozelimab + cemdisiran or placebo		Through week 24
Secondary	Incidence and severity of serious adverse events (SAEs) in patients treated with pozelimab + cemdisiran or placebo		Through week 24
Secondary	Incidence and severity of adverse events of special interest (AESIs) in patients treated with pozelimab + cemdisiran or placebo		Through week 24
Secondary	Concentrations of total pozelimab in serum		Through study duration, approximate 172 weeks
Secondary	Concentrations of cemdisiran and its metabolites in plasma		Through study duration, approximate 172 weeks
Secondary	Incidence of treatment-emergent anti-drug antibodies (ADAs) to pozelimab over time		Through study duration, approximately 172 weeks
Secondary	Incidence of treatment-emergent ADAs to cemdisiran over time		Through study duration, approximate 172 weeks
Secondary	Change in CH50 over time		Through study duration, approximately 172 weeks
Secondary	Percent change in CH50 over time		Through study duration, approximately 172 weeks

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