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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04432584




Registration number
NCT04432584
Ethics application status
Date submitted
3/06/2020
Date registered
16/06/2020
Date last updated
28/10/2020

Titles & IDs
Public title
A Study Evaluating The Efficacy And Safety Of Crovalimab Versus Eculizumab In Adult And Adolescent Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently 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) Currently Treated With Complement Inhibitors.
Secondary ID [1] 0 0
2020-000597-26
Secondary ID [2] 0 0
BO42161
Universal Trial Number (UTN)
Trial acronym
COMMODORE 1
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 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.

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.

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.


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 900 mg every 2 weeks, 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
Mean Percentage Change in Lactate Dehydrogenase (LDH) levels
Timepoint [1] 0 0
Baseline up to Week 25
Secondary outcome [1] 0 0
Percentage of Participants who achieve Transfusion Avoidance (TA) - TA is defined as participants who are packed RBC transfusion-free and do not require transfusion per protocol-specified guidelines.
Timepoint [1] 0 0
Baseline through Week 25
Secondary outcome [2] 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 [2] 0 0
Baseline through Week 25
Secondary outcome [3] 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 [3] 0 0
Baseline through Week 25
Secondary outcome [4] 0 0
Mean Change in Fatigue - Assessed by the FACIT-Fatigue Questionnaire (for adults aged >= 18 years).
Timepoint [4] 0 0
Baseline up to Week 25
Secondary outcome [5] 0 0
Percentage of Participants with Adverse Events (AEs) - Determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5 (CTCAE v5).
Timepoint [5] 0 0
Up to 2.5 years
Secondary outcome [6] 0 0
Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including meningococcal meningitis)
Timepoint [6] 0 0
Up to 2.5 years
Secondary outcome [7] 0 0
Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation
Timepoint [7] 0 0
Up to 2.5 years
Secondary outcome [8] 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 or ravulizumab treatment
Timepoint [8] 0 0
Up to 2.5 years
Secondary outcome [9] 0 0
Serum Concentrations of Crovalimab or Eculizumab over time
Timepoint [9] 0 0
Up to 2.5 years
Secondary outcome [10] 0 0
Serum Concentrations of Ravulizumab at the time of Crovalimab Initiation
Timepoint [10] 0 0
Baseline
Secondary outcome [11] 0 0
Percentage of Participants with Anti-Crovalimab Antibodies
Timepoint [11] 0 0
Up to 2.5 years
Secondary outcome [12] 0 0
Change in PD biomarkers including complement activity over time - Assessed by a Liposome Immunoassay (LIA) and total C5 concentration
Timepoint [12] 0 0
Up to 2.5 years
Secondary outcome [13] 0 0
Change over time in free C5 concentration in crovalimab-treated participants
Timepoint [13] 0 0
Up to 2.5 years
Secondary outcome [14] 0 0
Observed Value in Reticulocyte Count (count/mL)
Timepoint [14] 0 0
Up to 2.5 years
Secondary outcome [15] 0 0
Observed Value in Free Hemoglobin and Haptoglobin (mg/dL)
Timepoint [15] 0 0
Up to 2.5 years
Secondary outcome [16] 0 0
Change in Reticulocyte Count (count/mL)
Timepoint [16] 0 0
Baseline up to Week 25
Secondary outcome [17] 0 0
Change in Free Hemoglobin and Haptoglobin (mg/dL)
Timepoint [17] 0 0
Baseline up to Week 25

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

- Women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraception during the treatment period and for 6
months after the final dose of crovalimab or for 3 months after the final dose of
eculizumab.
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of allogeneic bone marrow transplantation.

- Pregnant or breastfeeding, or intending to become pregnant during the study or within
6 months after the final dose of 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 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 current trial.

- 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 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
Michigan
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
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Wisconsin
Country [8] 0 0
Belgium
State/province [8] 0 0
Bruxelles
Country [9] 0 0
Belgium
State/province [9] 0 0
Roeselare
Country [10] 0 0
Belgium
State/province [10] 0 0
Yvoir
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
PA
Country [14] 0 0
Brazil
State/province [14] 0 0
PR
Country [15] 0 0
Brazil
State/province [15] 0 0
RS
Country [16] 0 0
Brazil
State/province [16] 0 0
SC
Country [17] 0 0
Brazil
State/province [17] 0 0
SP
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
Colombia
State/province [19] 0 0
Bogota
Country [20] 0 0
Colombia
State/province [20] 0 0
Medellin
Country [21] 0 0
France
State/province [21] 0 0
Lille
Country [22] 0 0
France
State/province [22] 0 0
Marseille
Country [23] 0 0
France
State/province [23] 0 0
Rennes cedex 9
Country [24] 0 0
Germany
State/province [24] 0 0
Aachen
Country [25] 0 0
Germany
State/province [25] 0 0
Essen
Country [26] 0 0
Germany
State/province [26] 0 0
Riesa
Country [27] 0 0
Germany
State/province [27] 0 0
Ulm
Country [28] 0 0
Greece
State/province [28] 0 0
Alexandroupolis
Country [29] 0 0
Greece
State/province [29] 0 0
Athens
Country [30] 0 0
Greece
State/province [30] 0 0
Larissa
Country [31] 0 0
Greece
State/province [31] 0 0
Thessaloniki
Country [32] 0 0
Greece
State/province [32] 0 0
????a
Country [33] 0 0
Hungary
State/province [33] 0 0
Budapest
Country [34] 0 0
Israel
State/province [34] 0 0
Haifa
Country [35] 0 0
Italy
State/province [35] 0 0
Campania
Country [36] 0 0
Italy
State/province [36] 0 0
Emilia-Romagna
Country [37] 0 0
Italy
State/province [37] 0 0
Lazio
Country [38] 0 0
Italy
State/province [38] 0 0
Molise
Country [39] 0 0
Italy
State/province [39] 0 0
Piemonte
Country [40] 0 0
Italy
State/province [40] 0 0
Sicilia
Country [41] 0 0
Italy
State/province [41] 0 0
Toscana
Country [42] 0 0
Italy
State/province [42] 0 0
Veneto
Country [43] 0 0
Japan
State/province [43] 0 0
Aichi
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Japan
State/province [44] 0 0
Hokkaido
Country [45] 0 0
Japan
State/province [45] 0 0
Hyogo
Country [46] 0 0
Japan
State/province [46] 0 0
Ibaraki
Country [47] 0 0
Japan
State/province [47] 0 0
Ishikawa
Country [48] 0 0
Japan
State/province [48] 0 0
Mie
Country [49] 0 0
Japan
State/province [49] 0 0
Nagano
Country [50] 0 0
Japan
State/province [50] 0 0
Nagasaki
Country [51] 0 0
Japan
State/province [51] 0 0
Okayama
Country [52] 0 0
Japan
State/province [52] 0 0
Osaka
Country [53] 0 0
Japan
State/province [53] 0 0
Oshu
Country [54] 0 0
Japan
State/province [54] 0 0
Tokyo
Country [55] 0 0
Japan
State/province [55] 0 0
Toyama
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Seoul
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Ulsan
Country [58] 0 0
Mexico
State/province [58] 0 0
Nuevo LEON
Country [59] 0 0
Netherlands
State/province [59] 0 0
Amsterdam
Country [60] 0 0
Netherlands
State/province [60] 0 0
NL -nijmegen
Country [61] 0 0
Poland
State/province [61] 0 0
Bydgoszcz
Country [62] 0 0
Poland
State/province [62] 0 0
Gdansk
Country [63] 0 0
Poland
State/province [63] 0 0
Krakow
Country [64] 0 0
Poland
State/province [64] 0 0
Skórzewo
Country [65] 0 0
Poland
State/province [65] 0 0
Warszawa
Country [66] 0 0
Poland
State/province [66] 0 0
Wroclaw
Country [67] 0 0
Poland
State/province [67] 0 0
Zabrze
Country [68] 0 0
Portugal
State/province [68] 0 0
Porto
Country [69] 0 0
Singapore
State/province [69] 0 0
Singapore
Country [70] 0 0
Spain
State/province [70] 0 0
Asturias
Country [71] 0 0
Spain
State/province [71] 0 0
Barcelona
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Spain
State/province [72] 0 0
Madrid
Country [73] 0 0
Spain
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Vizcaya
Country [74] 0 0
Spain
State/province [74] 0 0
Caceres
Country [75] 0 0
Spain
State/province [75] 0 0
Las Palmas
Country [76] 0 0
Spain
State/province [76] 0 0
Salamanca
Country [77] 0 0
Spain
State/province [77] 0 0
Sevilla
Country [78] 0 0
Spain
State/province [78] 0 0
Toledo
Country [79] 0 0
Spain
State/province [79] 0 0
Valencia
Country [80] 0 0
Spain
State/province [80] 0 0
Zaragoza
Country [81] 0 0
Sweden
State/province [81] 0 0
Uppsala
Country [82] 0 0
Taiwan
State/province [82] 0 0
Chang Hua
Country [83] 0 0
Taiwan
State/province [83] 0 0
Hualien City
Country [84] 0 0
Taiwan
State/province [84] 0 0
Liuying Township
Country [85] 0 0
Taiwan
State/province [85] 0 0
Taipei
Country [86] 0 0
Taiwan
State/province [86] 0 0
Zhongshan Dist.
Country [87] 0 0
Turkey
State/province [87] 0 0
Ankara
Country [88] 0 0
Turkey
State/province [88] 0 0
Gaziantep
Country [89] 0 0
Turkey
State/province [89] 0 0
Istanbul
Country [90] 0 0
Turkey
State/province [90] 0 0
Izmir
Country [91] 0 0
Turkey
State/province [91] 0 0
Samsun
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Leeds
Country [93] 0 0
United Kingdom
State/province [93] 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
A study designed to evaluate the non-inferiority of crovalimab compared with eculizumab in
participants with PNH switching from eculizumab. This study will enroll approximately 250
participants randomized in a 1:1 ratio to the two arms.
Trial website
https://clinicaltrials.gov/show/NCT04432584
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: BO42161 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/NCT04432584