A Study Evaluating The Safety, Pharmacokinetics, and Efficacy Of Crovalimab Versus Eculizumab In Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

— COMMODORE 1  

Official title:

A Phase III, Randomized, Open-Label, Active-Controlled, Multicenter Study Evaluating The Safety, Pharmacokinetics, Pharmacodynamic And Efficacy of Crovalimab Versus Eculizumab In Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04432584
• Other study ID #: BO42161
• Secondary ID: 2020-000597-26
• Status: Recruiting
• Phase: Phase 3
• Start date: September 30, 2020
• Est. completion date: September 1, 2029

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BO42161 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study designed to evaluate the safety of crovalimab with eculizumab in participants with PNH currently treated with complement inhibitors. This study will enroll approximately 190 participants.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 190
• Est. completion date: September 1, 2029
• Est. primary completion date: September 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Body weight >= 40 kg at screening.
• Treated with eculizumab or ravulizumab for PNH for at least 3 months prior to Day 1.
• Lactate Dehydrogenase Levels =< 2x the upper limit of normal (ULN) at screening.
• Willingness and ability to comply with all study visits and procedures.
• Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry.
• Vaccination against Neisseria meningitidis serotypes A, C, W, and Y < 3 years prior to initiation of study treatment; or, if not previously done, vaccination administered no later than one week after the first drug administration.
• Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 10.5 months after the final dose of crovalimab or for 3 months after the final dose of eculizumab (or longer if required by the local product label).

Exclusion Criteria:

• History of allogeneic bone marrow transplantation.
• History of myelodysplastic syndrome with Revised International Prognostic Scoring System (IPSS-R) prognostic risk categories of intermediate, high and very high.
• Pregnant or breastfeeding, or intending to become pregnant during the study, within 10.5 months after the final dose of crovalimab, or 3 months after the final dose of eculizumab (or longer if required by the local product label).
• Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within 5 half-lives of that investigational product, whichever was greater: participants enrolled in an eculizumab or ravulizumab interventional study are eligible provided they fulfill eligibility (e.g., are willing and able to comply with the study assessments) and stop their participation in current trial before randomisation/enrolment.
• Positive for Active Hepatitis B and C infection (HBV/HCV).
• Concurrent disease, treatment, procedure, or surgery or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose any additional risk for the participant, or would, in the opinion of the investigator, preclude the participant's safe participation in and completion of the study.
• History of or ongoing cryoglobulinemia at screening.

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria

Intervention

Drug:
• Crovalimab
Crovalimab will be administered at a dose of 1000 mg IV (for participants with body weight between 40 and 100kg) or 1500 mg IV (for participants with body weight >=100kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, it will be administered at a dose of 340 mg SC. For Week 5 and Q4W thereafter, it will be administered at a dose of 680 mg SC (for participants with body weight between 40 and 100kg) or 1020 mg SC (for participants with body weight >=100kg). Dosing schedule will be as described above.
• Eculizumab
Eculizumab will be administered at a dose of 900 mg every 2 weeks, as per the dosing schedule described above.

Locations

Country	Name	City	State
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	Cliniques Universitaires Saint-Luc; Pharmacy	Bruxelles
Belgium	AZ Delta Campus Westlaan	Roeselare
Belgium	CHU UCL Namur / site Godinne	Yvoir
Brazil	Nucleo de Pesquisa Clinica do Hospital da Crianca	Brasilia	DF
Brazil	Hrpc - Health Clinical Research Representation - Eireli	Canoas	RS
Brazil	Centro Integrado de Oncologia de Curitiba	Curitiba	PR
Brazil	Hospital Universitario Walter Cantidio - UFC	Fortaleza	CE
Brazil	Fundação Doutor Amaral Carvalho	JAU	SP
Brazil	Instituto Joinvilense de Hematologia E Oncologia	Joinville	SC
Brazil	Elo Clinical Research	Maringa	PA
Brazil	Hospital de Clínicas de Porto Alegre X	Porto Alegre	RS
Brazil	Santa Casa de Misericordia de Porto Alegre	Porto Alegre	RS
Brazil	Hospital das Clínicas FMRP-USP	Ribeirao Preto	SP
Brazil	*X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia	Santo André	SP
Brazil	Hospital Paulistano	Sao Paulo	SP
Brazil	Hospital Sírio-Libanês	Sao Paulo	SP
Brazil	Beneficencia Portuguesa de Sao Paulo	São Paulo	SP
Brazil	Chronos Pesquisa Clinica	Taguatinga	DF
Canada	CISSS Chaudière-Appalaches	Levis	Quebec
Colombia	Fundacion Santa Fe de Bogota	Bogota
Czechia	Ustav hematologie a krevni transfuze	Praha
Estonia	North Estonia Medical Centre Foundation	Tallinn
France	Hopital Claude Huriez - CHU Lille	Lille
France	Institut Paoli Calmette; Service d'Hématologie Clinique	Marseille
France	CHU Rennes - Hopital Pontchaillou; Service d'Hémostase Bioclinique	Rennes cedex 9
Germany	Universitaetsklinikum Aachen AOeR	Aachen
Germany	Universitaetsklinikum	Essen
Germany	ELBLANDKLINIKUM Riesa	Riesa
Germany	Universitaetsklinikum Ulm	Ulm
Greece	University General Hospital of Alexandroupolis	Alexandroupolis
Greece	General Hospital of Athens LAIKO	Athens
Greece	Attikon University General Hospital	Chaidari
Greece	University General Hospital of Larissa	Larissa
Greece	General Hospital of Thessaloniki G. Papanikolaou	Thessaloniki
Hong Kong	The Chinese University of Hong Kong	Shatin
Hungary	Semmelweis Egyetem; Belgyogyaszati es Hematologiai Klinika	Budapest
Ireland	St James's Hospital	Dublin
Italy	Azienda Ospedaliera San Giuseppe Moscati	Avellino	Campania
Italy	Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele	Catania	Sicilia
Italy	Azienda Ospedaliera Universitaria Careggi	Florence	Toscana
Italy	Fondazione IRCCS CA? Granda Ospedale Maggiore Policlinico	Milano	Lombardia
Italy	Azienda Unita Sanitaria Locale- Ravenna	Ravenna	Emilia-Romagna
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Lazio
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino	Piemonte
Japan	Fujita Health University Hospital	Aichi
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Sapporo Medical University Hospital	Hokkaido
Japan	Kobe University Hospital; Medical Oncology and Hematology	Hyogo
Japan	Tokushukai Takasago Seibu Hospital	Hyogo
Japan	University of Tsukuba Hospital	Ibaraki
Japan	Ishikawa Prefectural Central Hospital	Ishikawa
Japan	Tokai University Hospital	Kanagawa
Japan	Mie University Hospital	Mie
Japan	Japanese Red Cross Society Suwa Hospital	Nagano
Japan	Nagasaki University Hospital	Nagasaki
Japan	Sasebo City General Hospital	Nagasaki
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	Osaka University Hospital	Osaka
Japan	Iwate Prefectural Isawa Hospital	Oshu
Japan	NTT Medical Center Tokyo	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
Japan	Toyama Prefectual Central Hospital	Toyama
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital; Yonsei University Health System	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan
Netherlands	Amsterdam UMC, Locatie AMC	Amsterdam
Poland	Szpital Uniwersytecki nr2 im. dr J. Biziela	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii	Gda?sk
Poland	SPZOZ Szpital Uniw W Krakowie	Krakow
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1	Lublin
Poland	Centrum Medyczne Pratia Poznan	Skórzewo
Poland	MTZ Clinical Research Powered by Pratia	Warszawa
Portugal	Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro	Aveiro
Portugal	Centro Hospitalar do Porto - Hospital de Santo António	Porto
Saudi Arabia	King Faisal Specialist Hospital & Research Center	Riyadh
Singapore	National University Hospital	Singapore
Spain	Hospital U. Central de Asturias	Asturias
Spain	ICO Badalona - Hospital Universitari Germans Trias i Pujol; Hematologia Clinica	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital de Basurto	Bilbao	Vizcaya
Spain	Hospital San Pedro de Alcantara	Caceres
Spain	Hospital Sant Joan De Deu	Esplugues De Llobregas	Barcelona
Spain	Hospital Universitario de Gran Canaria	Las Palmas de Gran Canaria	LAS Palmas
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Complejo Hospitalario Universitario de Santiago.	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Complejo Hospitalario de Toledo	Toledo
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Sweden	Akademiska Sjukhuset	Uppsala
Taiwan	Changhua Christian Hospital	Chang Hua
Taiwan	Hualien Tzu Chi Hospital; Hematology and oncology	Hualien City
Taiwan	Chi Mei Medical Center Liou Ying Campus	Liuying Township
Taiwan	National Taiwan Universtiy Hospital; Division of Hematology	Taipei
Taiwan	MacKay Memorial Hospital; Hematology and oncology	Zhongshan Dist.
Turkey	Hacettepe University Medical Faculty; Neurology	Ankara
Turkey	Gaziantep University Medical Faculty Sahinbey Educational Research Hospital; Hematology	Gaziantep
Turkey	Istanbul University Istanbul Medical Faculty; Neurology	Istanbul
Turkey	Marmara University Pendik Training and Research Hospital, Hematology Department	Istanbul
Turkey	Ege University Medical Faculty; Hematology	Izmir
Turkey	Ondokuz Mayis Univ. Med. Fac.	Samsun
United Kingdom	King'S College Hospital; Haematology	London
United States	The Oncology Institute of Hope and Innovation	Anaheim	California
United States	Carolinas Healthcare System	Charlotte	North Carolina
United States	Nationwide Children's Hospital; Dept. of Pulmonology	Columbus	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Cook Childrens Medical Center	Fort Worth	Texas
United States	Indiana Blood & Marrow Transplantation, LLC	Indianapolis	Indiana
United States	David Geffen School of Medicine UCLA	Los Angeles	California
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Chugai Pharmaceutical

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Colombia,  Czechia,  Estonia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Ireland,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Saudi Arabia,  Singapore,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events (AEs) and by Severity	Determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5 (CTCAE v5).	Up to approximately 8 years
Primary	Percentage of Participants with Injection- Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis)		Up to approximately 8 years
Primary	Percentage of Participants with Adverse Events (AEs) Leading to Study Drug Discontinuation		Up to approximately 8 years
Primary	Percentage of Participants with Clinical Manifestations of Drug-Target-Drug Complex (DTDC) Formation Amongst Those Participants who Switched to Crovalimab Treatment from Eculizumab Treatment or Ravulizumab Treatment		Up to approximately 8 years
Secondary	Serum Concentrations of Crovalimab or Eculizumab Over Time		Up to approximately 8 years
Secondary	Serum Concentrations of Ravulizumab at the time of Crovalimab Initiation		Baseline
Secondary	Percentage of Participants with Anti-Crovalimab Antibodies		Up to approximately 8 years
Secondary	Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time		Up to approximately 8 years
Secondary	Change Over Time in Free C5 Concentration in Crovalimab-Treated Participants		Up to approximately 8 years
Secondary	Observed Value in Reticulocyte Count (count/mL)		Up to approximately 8 years
Secondary	Observed Value in Free Hemoglobin and Haptoglobin (mg/dL)		Up to approximately 8 years
Secondary	Change in Reticulocyte Count (count/mL)		Baseline up to Week 25
Secondary	Absolute Change in Free Hemoglobin and Haptoglobin (mg/dL)		Baseline up to Week 25