A Phase III Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors. (COMMODORE 2)

February 23, 2024 updated by: Hoffmann-La Roche

A Phase III, Randomized, Open-Label, Active-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors.

A study designed to evaluate the non-inferiority of crovalimab compared with eculizumab in participants with PNH who have not been previously treated with complement inhibitor therapy.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

204

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Ciudad Autonoma Buenos Aires, Argentina, C1015ABO
        • Organizacion Medica de Investigacion (OMI)
  • Australia
    • New South Wales
      • Liverpool, New South Wales, Australia, 2170
        • Liverpool Hospital
  • Brazil
    • PR
      • Curitiba, PR, Brazil, 80810-050
        • Centro Integrado de Oncologia de Curitiba
    • RS
      • Porto Alegre, RS, Brazil
        • Hospital de Clínicas de Porto Alegre X
    • SP
      • Santo André, SP, Brazil, 09060-650
        • *X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
      • São Paulo, SP, Brazil, 01321-00
        • Beneficencia Portuguesa de Sao Paulo
  • China
      • Beijing City, China, 100032
        • Peking Union Medical College Hospital
      • Guangzhou, China, 510515
        • Nanfang Hospital, Southern Medical University
      • Hangzhou City, China, 310003
        • The First Affiliated Hospital, Zhejiang University
      • Nanjing, China, 210008
        • Jiangsu Province Hospital
      • Nantong City, China, 226001
        • Affiliated Hospital of Nantong University; Nephrology
      • Shanghai City, China, 200040
        • Huashan Hospital, Fudan University
      • Wuhan City, China, 430023
        • Union Hospital Tongji Medical College Huazhong University Of Science And Technology
  • France
      • Lille, France, 59037
        • Hopital Claude Huriez - CHU Lille
      • Pierre Benite, France, 69495
        • Centre Hospitalier Lyon Sud
  • Germany
      • Essen, Germany, 45147
        • Universitaetsklinkm
      • Ulm, Germany, 89081
        • Universitaetsklinikum Ulm
  • Greece
      • Thessaloniki, Greece, 57010
        • General Hospital of Thessaloniki G. Papanikolaou
  • Hong Kong
      • Shatin, Hong Kong
        • The Chinese University of Hong Kong; Department of Medicine & Therapeutics
  • Japan
      • Hokkaido, Japan, 060-8543
        • Sapporo Medical University Hospital
      • Ibaraki, Japan, 305-8576
        • University of Tsukuba Hospital
      • Tokyo, Japan, 160-0023
        • Tokyo Medical University Hospital
      • Tokyo, Japan, 141-8625
        • NTT Medical Center Tokyo
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
  • Lithuania
      • Vilnius, Lithuania, LT-08661
        • Vilnius University Hospital Santariskiu Clinics, Public Institution; Cardiology
  • Malaysia
      • Ampang, Malaysia, 68000
        • Hospital Ampang
      • Penang, Malaysia, 10990
        • Hospital Pulau Pinang
    • Pahang
      • Kuantan, Pahang, Malaysia, 25100
        • Hospital Tengku Ampuan Afzan
    • Perak
      • Ipoh, Perak, Malaysia, 30990
        • Hospital Raja Permaisuri Bainun
  • Mexico
      • Mexico, Mexico
        • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
    • Nuevo LEON
      • Monterrey, Nuevo LEON, Mexico, 64718
        • Global Trial Research Center S.A. de C.V.
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Amsterdam UMC, Locatie AMC
  • Philippines
      • Lipa City, Philippines, 4217
        • Mary Mediatrix Medical Center
      • Manila, Philippines, 1000
        • Philippine General Hospital; Pulmonary Medicine
      • Quezon City, Philippines, 1102
        • St Lukes Medical Center
  • Poland
      • Bydgoszcz, Poland, 85-168
        • Szpital Uniwersytecki nr2 im. dr J. Biziela
      • Gdansk, Poland, 80-952
        • Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii
      • Lublin, Poland, 20-081
        • Samodzielny Publiczny Szpital Kliniczny nr 1
      • Skórzewo, Poland, 60-185
        • Centrum Medyczne Pratia Poznan
      • Warszawa, Poland, 02-172
        • MTZ Clinical Research powered by Pratia
  • Portugal
      • Aveiro, Portugal, 3814-501
        • Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro
      • Lisbon, Portugal, 1050-034
        • Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
      • Porto, Portugal, 4099-001
        • Centro Hospitalar do Porto - Hospital de Santo Antonio
  • Romania
      • Bucharest, Romania, 11172
        • Spitalul Universitar de Urgenta Bucuresti
      • Craiova, Romania, 200143
        • Spitalul Clinic Municipal Filantropia Craiova
  • Singapore
      • Singapore, Singapore, 169608
        • Singapore General Hospital; Department of Haematology
      • Singapore, Singapore, 117599
        • National University Hospital
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona
      • Caceres, Spain, 10003
        • Hospital San Pedro de Alcántara
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Maranon
      • Madrid, Spain, 28040
        • Hospital Universitario Clínico San Carlos
      • Madrid, Spain, 28034
        • Hospital Universitario La Paz
      • Salamanca, Spain, 37007
        • Hospital Universitario de Salamanca
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • ICO Badalona - Hospital Universitari Germans Trias i Pujol; Hematologia Clinica
    • LAS Palmas
      • Las Palmas de Gran Canaria, LAS Palmas, Spain, 35010
        • Hospital Universitario de Gran Canaria Doctor Negrín; Servicio de Hematología
    • Vizcaya
      • Bilbao, Vizcaya, Spain, 48013
        • Hospital de Basurto
  • Sweden
      • Uppsala, Sweden, 751 85
        • Akademiska Sjukhuset
  • Taiwan
      • Kaohisung, Taiwan, 833
        • Chang Gung Medical Foundation - Kaohsiung; Oncology
      • Taipei, Taiwan, 100
        • National Taiwan Universtiy Hospital; Division of Hematology
  • Thailand
      • Bangkok, Thailand, 10330
        • King Chulalongkorn Memorial Hospital
      • Bangkok, Thailand, 10700
        • Siriraj Hospital
      • Chiang Mai, Thailand, 50200
        • Maharaj Nakorn Chiang Mai Hospital
  • Turkey
      • Samsun, Turkey, 55139
        • Ondokuz Mayis Univ. Med. Fac.
  • Ukraine
    • KIEV Governorate
      • Kyiv, KIEV Governorate, Ukraine, 02091
        • Medical Center OK!Clinic+
      • Mykolaiv, KIEV Governorate, Ukraine, 54058
        • Mykolayiv Regional Hospital
  • United Kingdom
      • Leeds, United Kingdom, LS9 7TF
        • St James University Hospital
      • London, United Kingdom, SE5 9RS
        • Kings College Hospital; Kings Clinical Research Facility

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Body weight >= 40 kg at screening.
  • Willingness and ability to comply with all study visits and procedures.
  • Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry.
  • LDH level >= 2x ULN at screening (as per local assessment).
  • 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 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:

  • Current or previous treatment with a complement inhibitor.
  • History of allogeneic bone marrow transplantation.
  • History of Neisseria meningitidis infection within 6 months prior to screening and up to first study drug administration.
  • 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 is greater.
  • 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.
  • Splenectomy < 6 months before screening.
  • Positive for Active Hepatitis B and C infection (HBV/HCV).
  • History of or ongoing cryoglobulinemia at screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm C (Crovalimab) (Exploratory)
Paediatric 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 as specified in the respective arms.
Experimental: Arm A (Crovalimab)
Crovalimab will be administered at an initial loading dose of 1000 milligrams (mg) (for participants with body weight between 40 and 100 kg) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab will be administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 for a total of 24 weeks of study treatment. Participants may continue to receive crovalimab after 24 weeks of treatment up to maximum of 5 years.
Drug: Crovalimab
Crovalimab will be administered as specified in the respective arms.
Active Comparator: Arm B (Eculizumab)
Participants will receive loading dose of eculizumab 600 mg on Days 1, 8, 15, and 22, followed by maintenance dose of 900 mg on Day 29 and every 2 weeks (Q2W) thereafter until 24 weeks. Participants may switch to receive crovalimab after 24 weeks of eculizumab treatment.
Drug: Eculizumab
Eculizumab will be administered as specified in the respective arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants who achieve Transfusion Avoidance (TA)
Time Frame: Baseline through Week 25
TA is defined as patients who are packed Red Blood Cell (pRBC) transfusion-free and do not require transfusion per protocol-specified guidelines.
Baseline through Week 25
Percentage of Participants with hemolysis control
Time Frame: Week 5 through Week 25
Measured by LDH =< 1.5 x ULN (as measured at the central laboratory).
Week 5 through Week 25

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Reticulocyte Count (count/mL)
Time Frame: Baseline up to Week 25
Baseline up to Week 25
Percentage of Participants with Breakthrough Hemolysis (BTH)
Time Frame: Baseline through Week 25
BTH is defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin < 10 g/dL], a major adverse vascular event [MAVE; including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH >= 2 x ULN after prior reduction of LDH to =<1.5 x ULN on treatment.
Baseline through Week 25
Percentage of Participants with Stabilization of Hemoglobin
Time Frame: Baseline through Week 25
Stabilized hemoglobin is defined as avoidance of a >= 2 g/dL decrease in hemoglobin level from baseline, in the absence of transfusion.
Baseline through Week 25
Mean Change in Fatigue
Time Frame: Baseline up to Week 25
Assessed by the FACIT-Fatigue Questionnaire.
Baseline up to Week 25
Percentage of Participants with Adverse Events (AEs)
Time Frame: Up to 7 years
Determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.
Up to 7 years
Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including meningococcal meningitis)
Time Frame: Up to 7 years
Up to 7 years
Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation
Time Frame: Up to 7 years
Up to 7 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
Time Frame: Up to 6.5 years
Up to 6.5 years
Serum concentrations of crovalimab and eculizumab over time
Time Frame: Up to 6.5 years
Up to 6.5 years
Percentage of Participants with Anti-Crovalimab Antibodies
Time Frame: Up to 6.5 years
Up to 6.5 years
Change in PD biomarkers including complement activity (CH50) over time
Time Frame: Up to 6.5 years
Assessed by a Liposome Immunoassay (LIA) and total C5 concentration
Up to 6.5 years
Change over time in free C5 concentration in crovalimab-treated participants
Time Frame: Up to 6.5 years
Up to 6.5 years
Observed Value in Reticulocyte Count (count/mL)
Time Frame: Up to 6.5 years
Up to 6.5 years
Observed Value in Free Hemoglobin and Haptoglobin (mg/dL)
Time Frame: Up to 6.5 years
Up to 6.5 years
Change in Free Hemoglobin and Haptoglobin (mg/dL)
Time Frame: Baseline up to Week 25
Baseline up to Week 25

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Collaborators

Chugai Pharmaceutical

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 8, 2020

Primary Completion (Actual)

November 16, 2022

Study Completion (Estimated)

June 30, 2028

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 (Estimated)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 23, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BO42162
  • 2019-004931-21 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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