Generalized Myasthenia Gravis Clinical Trial
— NIMBLEOfficial title:
Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Symptomatic Generalized Myasthenia Gravis
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
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 |
Country | Name | City | State |
---|---|---|---|
Australia | Lyell McEwin Hospital | Elizabeth Vale | South Australia |
Australia | St Vincents Hospital Melbourne | Fitzroy | Victoria |
Australia | Perron Institute for Neurological and Translational Science | Nedlands | Western Australia |
Australia | Southern Neurology | Sydney | New South Wales |
Belgium | Université Libre de Bruxelles - Hôpital Erasme | Bruxelles | |
Belgium | UZ Antwerpen | Edegem | Antwerpen |
Belgium | AZ Sint-Lucas | Gent | Oost-Vlaanderen |
Belgium | Chu Charleroi | Lodelinsart | Hainaut |
Canada | University of Alberta | Edmonton | Alberta |
Canada | London Health Sciences Centre | London | Ontario |
Canada | Centre Hospitalier de l'Universite de Montreal (CHUM) | Montreal | Quebec |
Canada | Toronto General Hospital | Toronto | Ontario |
Czechia | Fakultni Nemocnice Brno | Brno | Jihomoravsky Kraj |
Czechia | Fakultni nemocnice Ostrava | Ostrava | Moravskoslezský Kraj |
Denmark | Aalborg Universitetshospital | Aalborg | Nordjylland |
Denmark | Aarhus University Hospital | Aarhus N | |
Denmark | Copenhagen Neuromuscular Clinic at Rigshospitalet | Copenhagen | |
Denmark | Odense Universitetshospital - Infektionsmedicinsk Afdeling | Odense | |
France | CHU Bicêtre | Le Kremlin-Bicêtre | |
France | Centre Hospitalier Universitaire (CHU) de Nice | Nice | Alpes-Maritimes |
France | Hôpital de la Pitié Salpétrière | Paris | |
France | Centre Hospitalier Regional Universitaire (CHRU) de Nancy | Vandoeuvre Les Nancy | |
Georgia | Israeli-Georgian Medical Research Clinic HEALTHYCORE | T'bilisi | |
Georgia | LTD Academician N. Kipshidze Central University Clinic | 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 | |
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 | Kasturba Medical College (KMC) - Udupi | Bangalore | Karnataka |
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 (AIMS) and Research Centre | Kochi | Kerela |
India | Polakulath Narayanan Renai Medicity Multi Specialty Hospital, Kochi | Kochi | Punjab |
India | Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) | Lucknow | Uttar Pradesh |
India | Christian Medical College & Hospital | Ludhiana | Punjab |
India | All India Institute of Medical Sciences New Delhi | New 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 | |
Italy | IRCCS Mondino Foundation | Pavia | Lombardia |
Italy | Azienda Ospedaliero Universitaria Pisana | Pisa | Toscana |
Italy | Azienda Ospedaliera Sant'andrea | Roma | Lazio |
Italy | Universita' Degli Studi La Sapienza | Roma | Lazio |
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 | Osaka Red Cross Hospital - Neurology | Osaka | |
Japan | Okinawa Prefectural Nanbu Medical Center and Children's Medical Center | Shimajiri-Gun | |
Japan | Tokyo Medical University Hospital | Shinjuku ku | Tokyo |
Japan | Yamaguchi University Hospital | Ube | Yamaguchi |
Korea, Republic of | Kyungpook National University Chilgok Hospital | Daegu | |
Korea, Republic of | Samsung Medical Center - PPDS | Seoul | Seoul Teugbyeolsi |
Poland | Gdanski Uniwersytet Medyczny | Gdansk | Pomorskie |
Poland | Centrum Neurologii Klinicznej, Krakowska Akademia Neurologii | Kraków | Malopolskie |
Poland | Clinical Research Center Spólka z Ograniczona Odpowiedzialnoscia, Medic-R Spólka Komandytowa | Poznan | Wielkopolskie |
Poland | NZOZ Neuro-kard | Poznan | Wielkopolska |
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 Medical Foundation Kaohsiung Chang Gung Memorial Hospital | Kaohsiung | |
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 | Taoyuan | |
Turkey | Dokuz Eylul University Medical Faculty | Balcova | 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 | Austin Neuromuscular Center | 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 | 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 | Evanston | Illinois |
United States | Nerve and Muscle Center of Texas | Houston | Texas |
United States | University of California, Irvine | Irvine | California |
United States | University of Southern California | Los Angeles | California |
United States | Diverse Clinical Research | Miami | Florida |
United States | Collier Neurologic Specialists LLC | Naples | Florida |
United States | Weill Cornell Medicine - Peripheral Neuropathy Center | New York | New York |
United States | Prairie Education and Research Cooperative | O'Fallon | Illinois |
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. - Clinedge - PPDS | Rolling Meadows | Illinois |
United States | University of South Florida | Tampa | Florida |
Lead Sponsor | Collaborator |
---|---|
Regeneron Pharmaceuticals |
United States, Australia, Belgium, Canada, Czechia, Denmark, France, Georgia, Germany, India, Italy, Japan, Korea, Republic of, Poland, Serbia, Spain, Taiwan, Turkey, United Kingdom,
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 |
Status | Clinical Trial | Phase | |
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