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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04434092




Registration number
NCT04434092
Ethics application status
Date submitted
3/06/2020
Date registered
16/06/2020
Date last updated
1/12/2020

Titles & IDs
Public title
A Phase III Study Evaluating The Efficacy And Safety Of Crovalimab Versus Eculizumab In Adult And Adolescent Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors.
Scientific title
A Phase III, Randomized, Open-Label, Active-Controlled, Multicenter Study Evaluating The Efficacy And Safety Of Crovalimab Versus Eculizumab In Adult And Adolescent Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors.
Secondary ID [1] 0 0
2019-004931-21
Secondary ID [2] 0 0
BO42162
Universal Trial Number (UTN)
Trial acronym
COMMODORE 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Crovalimab
Treatment: Drugs - Eculizumab

Experimental: Arm A (Crovalimab) - Participants will receive an initial intravenous (IV) loading dose on Week 1 Day 1, followed by 4 weekly crovalimab subcutaneous (SC) doses on Week 1 Day 2, then on Weeks 2, 3 and 4. Maintenance dosing will begin at Week 5 and will continue Q4W (every 4 weeks) thereafter, for a total of at least 24 weeks of study treatment.

Active Comparator: Arm B (Eculizumab) - Participants will receive initial IV weekly doses for 4 weeks which will be followed by Q2W (every 2 weeks) IV administrations starting on Week 5.


Treatment: Drugs: 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.

Treatment: Drugs: Eculizumab
Eculizumab will be administered at a dose of 600 mg for the first 4 weeks, followed by maintenance doses of 900 mg starting on Week 5, as per the dosing schedule described above.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants who achieve Transfusion Avoidance (TA) - TA is defined as patients who are packed PBC (pRBC) transfusion-free and do not require transfusion per protocol-specified guidelines.
Timepoint [1] 0 0
Baseline through Week 25
Primary outcome [2] 0 0
Percentage of Participants with hemolysis control - Measured by LDH =< 1.5 x ULN (as measured at the central laboratory).
Timepoint [2] 0 0
Week 5 through Week 25
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline through Week 25
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline through Week 25
Secondary outcome [3] 0 0
Mean Change in Fatigue - Assessed by the FACIT-Fatigue Questionnaire (for adults aged >= 18 years).
Timepoint [3] 0 0
Baseline up to Week 25
Secondary outcome [4] 0 0
Percentage of Participants with Adverse Events (AEs) - Determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.
Timepoint [4] 0 0
Up to 2.5 years
Secondary outcome [5] 0 0
Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including meningococcal meningitis)
Timepoint [5] 0 0
Up to 2.5 years
Secondary outcome [6] 0 0
Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation
Timepoint [6] 0 0
Up to 2.5 years
Secondary outcome [7] 0 0
Percentage of Participants with clinical manifestations of Drug-Target-Drug Complex (DTDC) formation amongst those participants who switched to crovalimab treatment from eculizumab treatment
Timepoint [7] 0 0
Up to 2.5 years
Secondary outcome [8] 0 0
Serum concentrations of crovalimab and eculizumab over time
Timepoint [8] 0 0
Up to 2.5 years
Secondary outcome [9] 0 0
Percentage of Participants with Anti-Crovalimab Antibodies
Timepoint [9] 0 0
Up to 2.5 years
Secondary outcome [10] 0 0
Change in PD biomarkers including complement activity over time - Assessed by a Liposome Immunoassay (LIA) and total C5 concentration
Timepoint [10] 0 0
Up to 2.5 years
Secondary outcome [11] 0 0
Change over time in free C5 concentration in crovalimab-treated participants
Timepoint [11] 0 0
Up to 2.5 years
Secondary outcome [12] 0 0
Observed Value in Reticulocyte Count (count/mL)
Timepoint [12] 0 0
Up to 2.5 years
Secondary outcome [13] 0 0
Observed Value in Free Hemoglobin and Haptoglobin (mg/dL)
Timepoint [13] 0 0
Up to 2.5 years
Secondary outcome [14] 0 0
Change in Reticulocyte Count (count/mL)
Timepoint [14] 0 0
Baseline up to Week 25
Secondary outcome [15] 0 0
Change in Free Hemoglobin and Haptoglobin (mg/dL)
Timepoint [15] 0 0
Baseline up to Week 25

Eligibility
Key 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 < 3 years prior to initiation of study
treatment.

- Women of childbearing potential: agreement to remain abstinent or use contraception.
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

- Pregnant or breastfeeding, or intention of becoming pregnant during the study or
within 6 months after the final dose of the study treatment.

- 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Westmead Hospital; Pharmacy - Northmead
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2145 - Northmead
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Argentina
State/province [6] 0 0
Buenos Aires
Country [7] 0 0
Argentina
State/province [7] 0 0
Caba
Country [8] 0 0
Argentina
State/province [8] 0 0
Ciudad Autonoma Buenos Aires
Country [9] 0 0
Argentina
State/province [9] 0 0
Cordoba
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Brazil
State/province [11] 0 0
CE
Country [12] 0 0
Brazil
State/province [12] 0 0
DF
Country [13] 0 0
Brazil
State/province [13] 0 0
MG
Country [14] 0 0
Brazil
State/province [14] 0 0
PA
Country [15] 0 0
Brazil
State/province [15] 0 0
PR
Country [16] 0 0
Brazil
State/province [16] 0 0
RS
Country [17] 0 0
Brazil
State/province [17] 0 0
SC
Country [18] 0 0
Brazil
State/province [18] 0 0
SP
Country [19] 0 0
Canada
State/province [19] 0 0
Alberta
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
China
State/province [21] 0 0
Beijing City
Country [22] 0 0
China
State/province [22] 0 0
Dalian City
Country [23] 0 0
China
State/province [23] 0 0
Hangzhou
Country [24] 0 0
China
State/province [24] 0 0
Nanjing
Country [25] 0 0
China
State/province [25] 0 0
Nantong City
Country [26] 0 0
China
State/province [26] 0 0
Shanghai City
Country [27] 0 0
Colombia
State/province [27] 0 0
Bogota
Country [28] 0 0
Colombia
State/province [28] 0 0
Medellin
Country [29] 0 0
Czechia
State/province [29] 0 0
Praha
Country [30] 0 0
France
State/province [30] 0 0
Lille
Country [31] 0 0
France
State/province [31] 0 0
Marseille
Country [32] 0 0
France
State/province [32] 0 0
Pierre Benite
Country [33] 0 0
Germany
State/province [33] 0 0
Essen
Country [34] 0 0
Germany
State/province [34] 0 0
Riesa
Country [35] 0 0
Germany
State/province [35] 0 0
Ulm
Country [36] 0 0
Greece
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Alexandroup
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Greece
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Athens
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Greece
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Ioannina
Country [39] 0 0
Greece
State/province [39] 0 0
Thessaloniki
Country [40] 0 0
Greece
State/province [40] 0 0
????a
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Hong Kong
State/province [41] 0 0
Shatin
Country [42] 0 0
Hungary
State/province [42] 0 0
Budapest
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Italy
State/province [43] 0 0
Emilia-Romagna
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Italy
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Lazio
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Italy
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Molise
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Italy
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Piemonte
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Italy
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Sicilia
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Italy
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Toscana
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Italy
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Veneto
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Hokkaido
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Ibaraki
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Osaka
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Japan
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Tokyo
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Korea, Republic of
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Daegu
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Korea, Republic of
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Seoul
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Malaysia
State/province [56] 0 0
Kelantan
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Malaysia
State/province [57] 0 0
Penang
Country [58] 0 0
Malaysia
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Perak
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Malaysia
State/province [59] 0 0
Ampang
Country [60] 0 0
Malaysia
State/province [60] 0 0
Kuala Lumpur
Country [61] 0 0
Malaysia
State/province [61] 0 0
Pahang
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Mexico
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Nuevo LEON
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Mexico
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Mexico
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Mexico
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Monterrey
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Netherlands
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Amsterdam
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Netherlands
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NL -nijmegen
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Peru
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Lima
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Philippines
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Cebu
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Philippines
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Lipa City
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Philippines
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Manila
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Philippines
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Quezon City
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Poland
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Bydgoszcz
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Gdansk
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Poland
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Krakow
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Skórzewo
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Warszawa
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Wroclaw
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Poland
State/province [78] 0 0
Zabrze
Country [79] 0 0
Portugal
State/province [79] 0 0
Lisboa
Country [80] 0 0
Portugal
State/province [80] 0 0
Lisbon
Country [81] 0 0
Portugal
State/province [81] 0 0
Porto
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Romania
State/province [82] 0 0
Bucharest
Country [83] 0 0
Romania
State/province [83] 0 0
Cluj-Napoca
Country [84] 0 0
Romania
State/province [84] 0 0
Craiova
Country [85] 0 0
Romania
State/province [85] 0 0
Oradea
Country [86] 0 0
Romania
State/province [86] 0 0
Sector 2
Country [87] 0 0
Romania
State/province [87] 0 0
Targu-mures
Country [88] 0 0
Singapore
State/province [88] 0 0
Singapore
Country [89] 0 0
South Africa
State/province [89] 0 0
Bloemfontein
Country [90] 0 0
South Africa
State/province [90] 0 0
Johannesburg
Country [91] 0 0
Spain
State/province [91] 0 0
Asturias
Country [92] 0 0
Spain
State/province [92] 0 0
Barcelona
Country [93] 0 0
Spain
State/province [93] 0 0
Islas Baleares
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Spain
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LAS Palmas
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Spain
State/province [95] 0 0
Tenerife
Country [96] 0 0
Spain
State/province [96] 0 0
Vizcaya
Country [97] 0 0
Spain
State/province [97] 0 0
Caceres
Country [98] 0 0
Spain
State/province [98] 0 0
Madrid
Country [99] 0 0
Spain
State/province [99] 0 0
Salamanca
Country [100] 0 0
Spain
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Sevilla
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Spain
State/province [101] 0 0
Valencia
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Spain
State/province [102] 0 0
Valladolid
Country [103] 0 0
Spain
State/province [103] 0 0
Zaragoza
Country [104] 0 0
Sweden
State/province [104] 0 0
Uppsala
Country [105] 0 0
Taiwan
State/province [105] 0 0
Chang Hua
Country [106] 0 0
Taiwan
State/province [106] 0 0
Kaohisung
Country [107] 0 0
Taiwan
State/province [107] 0 0
Liuying Township
Country [108] 0 0
Taiwan
State/province [108] 0 0
Taipei
Country [109] 0 0
Taiwan
State/province [109] 0 0
Zhongshan Dist.
Country [110] 0 0
Thailand
State/province [110] 0 0
Bangkok
Country [111] 0 0
Thailand
State/province [111] 0 0
Chiang Mai
Country [112] 0 0
Turkey
State/province [112] 0 0
Ankara
Country [113] 0 0
Turkey
State/province [113] 0 0
Gaziantep
Country [114] 0 0
Turkey
State/province [114] 0 0
Istanbul
Country [115] 0 0
Turkey
State/province [115] 0 0
Izmir
Country [116] 0 0
Turkey
State/province [116] 0 0
Samsun
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Leeds
Country [118] 0 0
United Kingdom
State/province [118] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Chugai Pharmaceutical
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will enroll participants aged 12 years or older with a body weight >= 40 kg
diagnosed with PNH who have not been previously treated with complement inhibitor therapy.
Approximately 200 participants will be randomized in a 2:1 ratio into the following regimens:
[1] Crovalimab; [2] Eculizumab.
Trial website
https://clinicaltrials.gov/show/NCT04434092
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: BO42162 http://www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04434092