A Study Evaluating The Safety, Pharmacokinetics, and Efficacy Of Crovalimab Versus Eculizumab In Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors (COMMODORE 1)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: Crovalimab; Drug: Eculizumab

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BO42161 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Withdrawn
      • Liverpool Hospital
    • Westmead, New South Wales, Australia, 2145
      • Withdrawn
      • Westmead Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Withdrawn
      • Royal Perth Hospital
• Belgium
  • Bruxelles, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires Saint-Luc; Pharmacy
  • Roeselare, Belgium, 8800
    • Recruiting
    • AZ Delta Campus Westlaan
  • Yvoir, Belgium, B5530
    • Recruiting
    • CHU UCL Namur / site Godinne
• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60430-370
      • Active, not recruiting
      • Hospital Universitario Walter Cantidio - UFC
  • DF
    • Brasilia, DF, Brazil, 70684-831
      • Active, not recruiting
      • Nucleo de Pesquisa Clinica do Hospital da Crianca
    • Taguatinga, DF, Brazil, 72145-450
      • Active, not recruiting
      • Chronos Pesquisa Clínica
  • PA
    • Maringa, PA, Brazil, 87015-200
      • Withdrawn
      • Elo Clinical Research
  • PR
    • Curitiba, PR, Brazil, 80810-050
      • Recruiting
      • Centro Integrado de Oncologia de Curitiba
  • RS
    • Canoas, RS, Brazil, 92010-170
      • Withdrawn
      • Hrpc - Health Clinical Research Representation - Eireli
    • Porto Alegre, RS, Brazil, 90020-090
      • Active, not recruiting
      • Santa Casa de Misericordia de Porto Alegre
    • Porto Alegre, RS, Brazil
      • Active, not recruiting
      • Hospital de Clínicas de Porto Alegre X
  • SC
    • Joinville, SC, Brazil, 89201-260
      • Recruiting
      • Instituto Joinvilense de Hematologia e Oncologia
  • SP
    • JAU, SP, Brazil, 17210-120
      • Active, not recruiting
      • Fundacao Doutor Amaral Carvalho
    • Ribeirao Preto, SP, Brazil, 14048-900
      • Active, not recruiting
      • Hospital Das Clínicas Fmrp-Usp
    • Santo André, SP, Brazil, 09060-650
      • Active, not recruiting
      • *X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
    • Sao Paulo, SP, Brazil, 01321-000
      • Recruiting
      • Hospital Paulistano
    • Sao Paulo, SP, Brazil, 01308-050
      • Active, not recruiting
      • Hospital Sírio-Libanês
    • São Paulo, SP, Brazil, 01321-00
      • Recruiting
      • Beneficencia Portuguesa de Sao Paulo
• Canada
  • Quebec
    • Levis, Quebec, Canada, G6V 3Z1
      • Recruiting
      • CISSS Chaudière-Appalaches
• Colombia
  • Bogota, Colombia, 110111
    • Withdrawn
    • Fundacion Santa Fe de Bogota
• Czechia
  • Praha, Czechia, 128 00
    • Recruiting
    • Ustav hematologie a krevni transfuze
• Estonia
  • Tallinn, Estonia, 13419
    • Recruiting
    • North Estonia Medical Centre Foundation
• France
  • Lille, France, 59037
    • Recruiting
    • Hopital Claude Huriez - CHU Lille
  • Marseille, France, 13273
    • Recruiting
    • Institut Paoli Calmette; Service d'Hématologie Clinique
  • Rennes cedex 9, France, 35033
    • Recruiting
    • CHU Rennes - Hopital Pontchaillou; Service d'Hémostase Bioclinique
• Germany
  • Aachen, Germany, 52074
    • Recruiting
    • Universitaetsklinikum Aachen AOeR
  • Essen, Germany, 45147
    • Recruiting
    • Universitaetsklinikum
  • Riesa, Germany, 01589
    • Recruiting
    • Elblandklinikum Riesa
  • Ulm, Germany, 89081
    • Recruiting
    • Universitaetsklinikum Ulm
• Greece
  • Alexandroupolis, Greece, 681 00
    • Recruiting
    • University General Hospital of Alexandroupolis
  • Athens, Greece, 115 27
    • Recruiting
    • General Hospital of Athens Laiko
  • Chaidari, Greece, 124 62
    • Recruiting
    • Attikon University General Hospital
  • Larissa, Greece, 412 21
    • Withdrawn
    • University General Hospital of Larissa
  • Thessaloniki, Greece, 57010
    • Recruiting
    • General Hospital of Thessaloniki G. Papanikolaou
• Hong Kong
  • Shatin, Hong Kong, 123456
    • Recruiting
    • The Chinese University of Hong Kong
• Hungary
  • Budapest, Hungary, 1088
    • Recruiting
    • Semmelweis Egyetem; Belgyogyaszati es Hematologiai Klinika
• Ireland
  • Dublin, Ireland, 8
    • Recruiting
    • St James's Hospital
• Italy
  • Campania
    • Avellino, Campania, Italy, 83100
      • Active, not recruiting
      • Azienda Ospedaliera San Giuseppe Moscati
  • Emilia-Romagna
    • Ravenna, Emilia-Romagna, Italy, 48100
      • Recruiting
      • Azienda Unita Sanitaria Locale- Ravenna
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli Irccs
  • Molise
    • Milano, Molise, Italy, 20122
      • Recruiting
      • Fondazione IRCCS CA? Granda Ospedale Maggiore Policlinico
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • Recruiting
      • Azienda Ospedaliera Citta della Salute e della Scienza di Torino
  • Sicilia
    • Catania, Sicilia, Italy, 95123
      • Active, not recruiting
      • Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele
  • Toscana
    • Florence, Toscana, Italy, 50134
      • Recruiting
      • Azienda Ospedaliera Universitaria Careggi
• Japan
  • Aichi, Japan, 470-1192
    • Recruiting
    • Fujita Health University Hospital
  • Fukushima, Japan, 960-1295
    • Recruiting
    • Fukushima Medical University Hospital
  • Hokkaido, Japan, 060-8543
    • Withdrawn
    • Sapporo Medical University Hospital
  • Hyogo, Japan, 676-0812
    • Recruiting
    • Tokushukai Takasago Seibu Hospital
  • Hyogo, Japan, 650-0017
    • Completed
    • Kobe University Hospital; Medical Oncology and Hematology
  • Ibaraki, Japan, 305-8576
    • Withdrawn
    • University of tsukuba hospital
  • Ishikawa, Japan, 920-8530
    • Active, not recruiting
    • Ishikawa Prefectural Central Hospital
  • Kanagawa, Japan, 259-1193
    • Recruiting
    • Tokai University Hospital
  • Mie, Japan, 514-8507
    • Active, not recruiting
    • Mie University Hospital
  • Nagano, Japan, 392-8510
    • Recruiting
    • Japanese Red Cross Society Suwa Hospital
  • Nagasaki, Japan, 852-8501
    • Recruiting
    • Nagasaki University Hospital
  • Nagasaki, Japan, 857-8511
    • Recruiting
    • Sasebo City General Hospital
  • Okayama, Japan, 701-1192
    • Active, not recruiting
    • National Hospital Organization Okayama Medical Center
  • Osaka, Japan, 565-0871
    • Recruiting
    • Osaka University Hospital
  • Oshu, Japan, 023-0864
    • Active, not recruiting
    • Iwate Prefectural Isawa Hospital
  • Tokyo, Japan, 160-0023
    • Completed
    • Tokyo Medical University Hospital
  • Tokyo, Japan, 141-8625
    • Active, not recruiting
    • NTT Medical Center Tokyo
  • Toyama, Japan, 930-8550
    • Active, not recruiting
    • Toyama Prefectual Central Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital; Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Withdrawn
    • Asan Medical Center
  • Ulsan, Korea, Republic of, 44033
    • Recruiting
    • Ulsan University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Recruiting
    • Amsterdam UMC, locatie AMC
• Poland
  • Bydgoszcz, Poland, 85-168
    • Recruiting
    • Szpital Uniwersytecki nr2 im. dr J. Biziela
  • Gda?sk, Poland, 80-214
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii
  • Krakow, Poland, 31-501
    • Withdrawn
    • SPZOZ Szpital Uniw W Krakowie
  • Lublin, Poland, 20-081
    • Recruiting
    • Samodzielny Publiczny Szpital Kliniczny Nr 1
  • Skórzewo, Poland, 60-185
    • Recruiting
    • Centrum Medyczne Pratia Poznan
  • Warszawa, Poland, 02-172
    • Recruiting
    • MTZ Clinical Research Powered by Pratia
• Portugal
  • Aveiro, Portugal, 3814-501
    • Recruiting
    • Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro
  • Porto, Portugal, 4099-001
    • Active, not recruiting
    • Centro Hospitalar do Porto - Hospital de Santo António
• Saudi Arabia
  • Riyadh, Saudi Arabia, 12713
    • Recruiting
    • King Faisal Specialist Hospital & Research Center
• Singapore
  • Singapore, Singapore, 117599
    • Recruiting
    • National University Hospital
• Spain
  • Asturias, Spain, 33011
    • Recruiting
    • Hospital U. Central de Asturias
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Active, not recruiting
    • Hospital Clínic de Barcelona
  • Caceres, Spain, 10003
    • Recruiting
    • Hospital San Pedro de Alcántara
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Clinico San Carlos
  • Malaga, Spain, 29010
    • Recruiting
    • Hospital Regional Universitario de Malaga
  • Salamanca, Spain, 37007
    • Recruiting
    • Hospital Universitario de Salamanca
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen Del Rocio
  • Toledo, Spain, 45004
    • Recruiting
    • Complejo Hospitalario de Toledo
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Zaragoza, Spain, 50009
    • Recruiting
    • Hospital Universitario Miguel Servet
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Recruiting
      • ICO Badalona - Hospital Universitari Germans Trias i Pujol; Hematologia Clinica
    • Esplugues De Llobregas, Barcelona, Spain, 08950
      • Recruiting
      • Hospital Sant Joan de Déu
  • LA Coruña
    • Santiago de Compostela, LA Coruña, Spain, 5ºA
      • Recruiting
      • Complejo Hospitalario Universitario de Santiago.
  • LAS Palmas
    • Las Palmas de Gran Canaria, LAS Palmas, Spain, 35019
      • Recruiting
      • Hospital Universitario de Gran Canaria
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Recruiting
      • Hospital De Basurto
• Sweden
  • Uppsala, Sweden, 751 85
    • Recruiting
    • Akademiska Sjukhuset
• Taiwan
  • Chang Hua, Taiwan, 500
    • Recruiting
    • Changhua Christian Hospital
  • Hualien City, Taiwan, 97002
    • Recruiting
    • Hualien Tzu Chi Hospital; Hematology and oncology
  • Liuying Township, Taiwan, 736
    • Withdrawn
    • Chi Mei Medical Center Liou Ying Campus
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan Universtiy Hospital; Division of Hematology
  • Zhongshan Dist., Taiwan, 10449
    • Withdrawn
    • MacKay Memorial Hospital; Hematology and oncology
• Turkey
  • Ankara, Turkey, 06100
    • Recruiting
    • Hacettepe University Medical Faculty; Neurology
  • Gaziantep, Turkey, 27310
    • Recruiting
    • Gaziantep University Medical Faculty Sahinbey Educational Research Hospital; Hematology
  • Istanbul, Turkey, 34093
    • Recruiting
    • Istanbul University Istanbul Medical Faculty; Neurology
  • Istanbul, Turkey, 34300
    • Recruiting
    • Marmara University Pendik Training and Research Hospital, Hematology Department
  • Izmir, Turkey, 35040
    • Recruiting
    • Ege University Medical Faculty; Hematology
  • Samsun, Turkey, 55139
    • Recruiting
    • Ondokuz Mayis Univ. Med. Fac.
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • King'S College Hospital; Haematology
• United States
  • California
    • Anaheim, California, United States, 92801
      • Active, not recruiting
      • The Oncology Institute of Hope and Innovation
    • Los Angeles, California, United States, 90095
      • Recruiting
      • David Geffen School of Medicine UCLA
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Withdrawn
      • Indiana Blood & Marrow Transplantation, LLC
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28208
      • Recruiting
      • Carolinas Healthcare System
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital; Dept. of Pulmonology
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Cook Childrens Medical Center
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (Crovalimab); Participants will receive a loading series of crovalimab comprised of an intravenous (IV) dose on Day 1, followed by weekly crovalimab subcutaneous (SC) doses for 4 weeks on Week 1 Day 2, then on Weeks 2, 3, and 4. Maintenance SC dosing will begin at Week 5 and will continue Q4W (every 4 weeks) thereafter for a total of 24 weeks of study treatment. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.	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.
Active Comparator: Arm B (Eculizumab); Participants will receive an approved maintenance dose of eculizumab starting on Day 1 and Q2W (every 2 weeks) thereafter for a total of 24 weeks of study treatment. After 24 weeks of study eculizumab treatment, participants will have the option to switch to crovalimab or to discontinue from the study after completion of 10 weeks of safety follow-up.	Drug: Eculizumab; Eculizumab will be administered at a dose of 900 mg every 2 weeks, as per the dosing schedule described above.
Experimental: Arm C (Crovalimab) (Exploratory); Participants will receive a loading series of Crovalimab comprised of an IV dose on Week 1 Day 1, followed by weekly crovalimab SC doses for 4 weeks on Week 1 (Day 2) then on Weeks 2, 3, and 4. Maintenance SC dosing will begin at Week 5 and will be administered Q4W thereafter. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Percentage of Participants with Injection- Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis)		Up to approximately 8 years
Percentage of Participants with Adverse Events (AEs) Leading to Study Drug Discontinuation		Up to approximately 8 years
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 Outcome Measures

Outcome Measure	Time Frame
Serum Concentrations of Crovalimab or Eculizumab Over Time	Up to approximately 8 years
Serum Concentrations of Ravulizumab at the time of Crovalimab Initiation	Baseline
Percentage of Participants with Anti-Crovalimab Antibodies	Up to approximately 8 years
Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time	Up to approximately 8 years
Change Over Time in Free C5 Concentration in Crovalimab-Treated Participants	Up to approximately 8 years
Observed Value in Reticulocyte Count (count/mL)	Up to approximately 8 years
Observed Value in Free Hemoglobin and Haptoglobin (mg/dL)	Up to approximately 8 years
Change in Reticulocyte Count (count/mL)	Baseline up to Week 25
Absolute Change in Free Hemoglobin and Haptoglobin (mg/dL)	Baseline up to Week 25

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Chugai Pharmaceutical
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hemoglobinuria; Hemoglobinuria, Paroxysmal; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: BO42161; 2020-000597-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No