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.

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

— COMMODORE 2  

Official title:

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04434092
• Other study ID #: BO42162
• Secondary ID: 2019-004931-21
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 8, 2020
• Est. completion date: June 30, 2028

Study information

• Verified date: February 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 204
• Est. completion date: June 30, 2028
• Est. primary completion date: November 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria

Intervention

Drug:
• Crovalimab
Crovalimab will be administered as specified in the respective arms.
• Eculizumab
Eculizumab will be administered as specified in the respective arm.

Locations

Country	Name	City	State
Argentina	Organizacion Medica de Investigacion (OMI)	Ciudad Autonoma Buenos Aires
Australia	Liverpool Hospital	Liverpool	New South Wales
Brazil	Centro Integrado de Oncologia de Curitiba	Curitiba	PR
Brazil	Hospital de Clínicas de Porto Alegre X	Porto Alegre	RS
Brazil	*X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia	Santo André	SP
Brazil	Beneficencia Portuguesa de Sao Paulo	São Paulo	SP
China	Peking Union Medical College Hospital	Beijing City
China	Nanfang Hospital, Southern Medical University	Guangzhou
China	The First Affiliated Hospital, Zhejiang University	Hangzhou City
China	Jiangsu Province Hospital	Nanjing
China	Affiliated Hospital of Nantong University; Nephrology	Nantong City
China	Huashan Hospital, Fudan University	Shanghai City
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
France	Hopital Claude Huriez - CHU Lille	Lille
France	Centre Hospitalier Lyon Sud	Pierre Benite
Germany	Universitaetsklinkm	Essen
Germany	Universitaetsklinikum Ulm	Ulm
Greece	General Hospital of Thessaloniki G. Papanikolaou	Thessaloniki
Hong Kong	The Chinese University of Hong Kong; Department of Medicine & Therapeutics	Shatin
Japan	Sapporo Medical University Hospital	Hokkaido
Japan	University of Tsukuba Hospital	Ibaraki
Japan	NTT Medical Center Tokyo	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
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
Lithuania	Vilnius University Hospital Santariskiu Clinics, Public Institution; Cardiology	Vilnius
Malaysia	Hospital Ampang	Ampang
Malaysia	Hospital Raja Permaisuri Bainun	Ipoh	Perak
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan	Pahang
Malaysia	Hospital Pulau Pinang	Penang
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico
Mexico	Global Trial Research Center S.A. de C.V.	Monterrey	Nuevo LEON
Netherlands	Amsterdam UMC, Locatie AMC	Amsterdam
Philippines	Mary Mediatrix Medical Center	Lipa City
Philippines	Philippine General Hospital; Pulmonary Medicine	Manila
Philippines	St Lukes Medical Center	Quezon City
Poland	Szpital Uniwersytecki nr2 im. dr J. Biziela	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii	Gdansk
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	Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.	Lisbon
Portugal	Centro Hospitalar do Porto - Hospital de Santo António	Porto
Romania	Spitalul Universitar de Urgenta Bucuresti	Bucharest
Romania	Spitalul Clinic Municipal Filantropia Craiova	Craiova
Singapore	National University Hospital	Singapore
Singapore	Singapore General Hospital; Department of Haematology	Singapore
Spain	ICO Badalona - Hospital Universitari Germans Trias i Pujol; Hematologia Clinica	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de Basurto	Bilbao	Vizcaya
Spain	Hospital San Pedro de Alcantara	Caceres
Spain	Hospital Universitario de Gran Canaria Doctor Negrín; Servicio de Hematología	Las Palmas de Gran Canaria	LAS Palmas
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Sweden	Akademiska Sjukhuset	Uppsala
Taiwan	Chang Gung Medical Foundation - Kaohsiung; Oncology	Kaohisung
Taiwan	National Taiwan Universtiy Hospital; Division of Hematology	Taipei
Thailand	King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai
Turkey	Ondokuz Mayis Univ. Med. Fac.	Samsun
Ukraine	Medical Center OK!Clinic+	Kyiv	KIEV Governorate
Ukraine	Mykolayiv Regional Hospital	Mykolaiv	KIEV Governorate
United Kingdom	St James University Hospital	Leeds
United Kingdom	Kings College Hospital; Kings Clinical Research Facility	London

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Chugai Pharmaceutical

Countries where clinical trial is conducted

Argentina,  Australia,  Brazil,  China,  France,  Germany,  Greece,  Hong Kong,  Japan,  Korea, Republic of,  Lithuania,  Malaysia,  Mexico,  Netherlands,  Philippines,  Poland,  Portugal,  Romania,  Singapore,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants who achieve Transfusion Avoidance (TA)	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
Primary	Percentage of Participants with hemolysis control	Measured by LDH =< 1.5 x ULN (as measured at the central laboratory).	Week 5 through Week 25
Secondary	Percentage of Participants with Breakthrough Hemolysis (BTH)	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
Secondary	Percentage of Participants with Stabilization of Hemoglobin	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
Secondary	Mean Change in Fatigue	Assessed by the FACIT-Fatigue Questionnaire.	Baseline up to Week 25
Secondary	Percentage of Participants with Adverse Events (AEs)	Determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.	Up to 7 years
Secondary	Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including meningococcal meningitis)		Up to 7 years
Secondary	Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation		Up to 7 years
Secondary	Percentage of Participants with clinical manifestations of Drug-Target-Drug Complex (DTDC) formation amongst those participants who switched to crovalimab treatment from eculizumab treatment		Up to 6.5 years
Secondary	Serum concentrations of crovalimab and eculizumab over time		Up to 6.5 years
Secondary	Percentage of Participants with Anti-Crovalimab Antibodies		Up to 6.5 years
Secondary	Change in PD biomarkers including complement activity (CH50) over time	Assessed by a Liposome Immunoassay (LIA) and total C5 concentration	Up to 6.5 years
Secondary	Change over time in free C5 concentration in crovalimab-treated participants		Up to 6.5 years
Secondary	Observed Value in Reticulocyte Count (count/mL)		Up to 6.5 years
Secondary	Observed Value in Free Hemoglobin and Haptoglobin (mg/dL)		Up to 6.5 years
Secondary	Change in Reticulocyte Count (count/mL)		Baseline up to Week 25
Secondary	Change in Free Hemoglobin and Haptoglobin (mg/dL)		Baseline up to Week 25