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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04432584
Ethics application status
Date submitted
3/06/2020
Date registered
16/06/2020

Titles & IDs
Public title
A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Crovalimab Versus Eculizumab in 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 Safety, Pharmacokinetics, Pharmacodynamic and Efficacy of Crovalimab Versus Eculizumab in 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 every 4 weeks (Q4W) 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 every 2 weeks (Q2W) 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 with a body weight = 5 to \<12 kilograms (kg) will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by crovalimab SC dose on Day 2 Week 1. Maintenance doses will begin at Week 3 and will be administered Q2W, thereafter. Participants with a body weight = 12 to \< 20 kg and = 20 kg will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by weekly crovalimab SC doses for 4 weeks at Week 1 (Day 2) and then at Weeks 2, 3, and 4. Maintenance doses will begin at Week 5 and will be administered Q2W thereafter, for participants with a body weight = 12 to \< 20 kg and Q4W thereafter, for participants with a body weight \> 20 kg. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.


Treatment: Drugs: Crovalimab
Dosing depends on body weight. Participants will be dosed as follows:

* 5 kg to \< 12 kg: 100 mg IV on Week 1 Day 1 (W1D1); 85 mg SC on Week 1 Day 2 (W1D2) and Q2W from Week 3 until end of study
* 12 kg to \< 20 kg: 200 mg IV on W1D1; 85 mg SC on W1D2, Weeks 2, 3 and 4; 170 mg SC, Q2W from Week 5 until end of study
* 20 kg to \< 30 kg: 300 mg IV on W1D1; 85 mg SC on W1D2, Weeks 2, 3 and 4; 340 mg SC, Q4W from Week 5 until end of study
* 30 kg to \< 40 kg: 400 mg IV on W1D1; 170 mg SC on W1D2, Weeks 2, 3 and 4; 510 mg SC, Q4W from Week 5 until end of study
* 40 kg to \< 100 kg: 1000 mg IV on W1D1; 340 mg SC W1D2, Weeks 2, 3 and 4; 680 mg SC, Q4W from Week 5 until end of study
* 100 kg: 1500 mg IV on W1D1; 340 mg SC W1D2, Weeks 2, 3 and 4; 1020 mg SC, Q4W from Week 5 until end of study.

Treatment: Drugs: Eculizumab
Eculizumab will be administered at a dose of 900 mg Q2W, 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 With Adverse Events (AEs) and by Severity
Timepoint [1] 0 0
Up to approximately 6 years
Primary outcome [2] 0 0
Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis)
Timepoint [2] 0 0
Up to approximately 6 years
Primary outcome [3] 0 0
Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation
Timepoint [3] 0 0
Up to approximately 6 years
Primary outcome [4] 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 [4] 0 0
Up to approximately 6 years
Secondary outcome [1] 0 0
Serum Concentrations of Crovalimab or Eculizumab Over Time
Timepoint [1] 0 0
Up to approximately 6 years
Secondary outcome [2] 0 0
Serum Concentrations of Ravulizumab at the Time of Crovalimab Initiation
Timepoint [2] 0 0
Baseline
Secondary outcome [3] 0 0
Percentage of Participants With Anti-crovalimab Antibodies
Timepoint [3] 0 0
Up to approximately 6 years
Secondary outcome [4] 0 0
Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time
Timepoint [4] 0 0
Up to approximately 6 years
Secondary outcome [5] 0 0
Change Over Time in Free C5 Concentration in Crovalimab-treated Participants
Timepoint [5] 0 0
Up to approximately 6 years
Secondary outcome [6] 0 0
Observed Value in Reticulocyte Count (count/milliliters [mL])
Timepoint [6] 0 0
Up to approximately 6 years
Secondary outcome [7] 0 0
Observed Value in Free Hemoglobin and Haptoglobin (milligrams per deciliter [mg/dL])
Timepoint [7] 0 0
Up to approximately 6 years
Secondary outcome [8] 0 0
Absolute Change From Baseline in Reticulocyte Count (count/mL)
Timepoint [8] 0 0
Baseline up to Week 25
Secondary outcome [9] 0 0
Absolute Change From Baseline in Free Hemoglobin and Haptoglobin (mg/dL)
Timepoint [9] 0 0
Baseline up to Week 25

Eligibility
Key inclusion criteria
* Body weight = 40 kg at screening (pediatric participants with body weight < 40 kg)
* 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)
Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2027
Actual
Sample size
Target
190
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
North Carolina
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
Belgium
State/province [3] 0 0
Bruxelles
Country [4] 0 0
Belgium
State/province [4] 0 0
Roeselare
Country [5] 0 0
Belgium
State/province [5] 0 0
Yvoir
Country [6] 0 0
Brazil
State/province [6] 0 0
Distrito Federal
Country [7] 0 0
Brazil
State/province [7] 0 0
Rio Grande Do Sul
Country [8] 0 0
Brazil
State/province [8] 0 0
Santa Catarina
Country [9] 0 0
Brazil
State/province [9] 0 0
São Paulo
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
Czechia
State/province [11] 0 0
Praha
Country [12] 0 0
Estonia
State/province [12] 0 0
Tallinn
Country [13] 0 0
France
State/province [13] 0 0
Lille cedex
Country [14] 0 0
Germany
State/province [14] 0 0
Aachen
Country [15] 0 0
Germany
State/province [15] 0 0
Riesa
Country [16] 0 0
Greece
State/province [16] 0 0
Athens
Country [17] 0 0
Hong Kong
State/province [17] 0 0
Shatin
Country [18] 0 0
Hungary
State/province [18] 0 0
Budapest
Country [19] 0 0
Ireland
State/province [19] 0 0
Dublin
Country [20] 0 0
Italy
State/province [20] 0 0
Emilia-Romagna
Country [21] 0 0
Italy
State/province [21] 0 0
Lombardia
Country [22] 0 0
Italy
State/province [22] 0 0
Piemonte
Country [23] 0 0
Italy
State/province [23] 0 0
Toscana
Country [24] 0 0
Japan
State/province [24] 0 0
Aichi
Country [25] 0 0
Japan
State/province [25] 0 0
Hyogo
Country [26] 0 0
Japan
State/province [26] 0 0
Ishikawa
Country [27] 0 0
Japan
State/province [27] 0 0
Kanagawa
Country [28] 0 0
Japan
State/province [28] 0 0
Mie
Country [29] 0 0
Japan
State/province [29] 0 0
Nagano
Country [30] 0 0
Japan
State/province [30] 0 0
Nagasaki
Country [31] 0 0
Japan
State/province [31] 0 0
Okayama
Country [32] 0 0
Japan
State/province [32] 0 0
Osaka
Country [33] 0 0
Japan
State/province [33] 0 0
Oshu
Country [34] 0 0
Japan
State/province [34] 0 0
Tokyo
Country [35] 0 0
Japan
State/province [35] 0 0
Toyama
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Seoul
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Ulsan
Country [38] 0 0
Netherlands
State/province [38] 0 0
Amsterdam
Country [39] 0 0
Poland
State/province [39] 0 0
Bydgoszcz
Country [40] 0 0
Poland
State/province [40] 0 0
Gda?sk
Country [41] 0 0
Poland
State/province [41] 0 0
Lublin
Country [42] 0 0
Poland
State/province [42] 0 0
Skórzewo
Country [43] 0 0
Poland
State/province [43] 0 0
Warszawa
Country [44] 0 0
Portugal
State/province [44] 0 0
Aveiro
Country [45] 0 0
Saudi Arabia
State/province [45] 0 0
Riyadh
Country [46] 0 0
Singapore
State/province [46] 0 0
Singapore
Country [47] 0 0
Spain
State/province [47] 0 0
Barcelona
Country [48] 0 0
Spain
State/province [48] 0 0
LA Coruna
Country [49] 0 0
Spain
State/province [49] 0 0
Asturias
Country [50] 0 0
Spain
State/province [50] 0 0
Las Palmas
Country [51] 0 0
Spain
State/province [51] 0 0
Madrid
Country [52] 0 0
Spain
State/province [52] 0 0
Malaga
Country [53] 0 0
Spain
State/province [53] 0 0
Salamanca
Country [54] 0 0
Spain
State/province [54] 0 0
Sevilla
Country [55] 0 0
Spain
State/province [55] 0 0
Toledo
Country [56] 0 0
Spain
State/province [56] 0 0
Zaragoza
Country [57] 0 0
Sweden
State/province [57] 0 0
Uppsala
Country [58] 0 0
Taiwan
State/province [58] 0 0
Chang Hua
Country [59] 0 0
Taiwan
State/province [59] 0 0
Hualien
Country [60] 0 0
Taiwan
State/province [60] 0 0
Taipei
Country [61] 0 0
Turkey
State/province [61] 0 0
Ankara
Country [62] 0 0
Turkey
State/province [62] 0 0
Gaziantep
Country [63] 0 0
Turkey
State/province [63] 0 0
Istanbul
Country [64] 0 0
Turkey
State/province [64] 0 0
Izmir
Country [65] 0 0
Turkey
State/province [65] 0 0
Samsun
Country [66] 0 0
United Kingdom
State/province [66] 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
Trial website
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 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04432584