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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04434092
Ethics application status
Date submitted
3/06/2020
Date registered
16/06/2020

Titles & IDs
Public title
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.
Scientific 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.
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) - 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.

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.

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.


Treatment: Drugs: Crovalimab
Crovalimab will be administered as specified in the respective arms.

Treatment: Drugs: Eculizumab
Eculizumab will be administered as specified in the respective arm.
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)
Assessment method [1] 0 0
TA is defined as patients who are packed Red Blood Cell (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
Assessment method [2] 0 0
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)
Assessment method [1] 0 0
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
Assessment method [2] 0 0
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
Assessment method [3] 0 0
Assessed by the FACIT-Fatigue Questionnaire.
Timepoint [3] 0 0
Baseline up to Week 25
Secondary outcome [4] 0 0
Percentage of Participants with Adverse Events (AEs)
Assessment method [4] 0 0
Determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.
Timepoint [4] 0 0
Up to 7 years
Secondary outcome [5] 0 0
Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including meningococcal meningitis)
Assessment method [5] 0 0
Timepoint [5] 0 0
Up to 7 years
Secondary outcome [6] 0 0
Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation
Assessment method [6] 0 0
Timepoint [6] 0 0
Up to 7 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
Assessment method [7] 0 0
Timepoint [7] 0 0
Up to 6.5 years
Secondary outcome [8] 0 0
Serum concentrations of crovalimab and eculizumab over time
Assessment method [8] 0 0
Timepoint [8] 0 0
Up to 6.5 years
Secondary outcome [9] 0 0
Percentage of Participants with Anti-Crovalimab Antibodies
Assessment method [9] 0 0
Timepoint [9] 0 0
Up to 6.5 years
Secondary outcome [10] 0 0
Change in PD biomarkers including complement activity (CH50) over time
Assessment method [10] 0 0
Assessed by a Liposome Immunoassay (LIA) and total C5 concentration
Timepoint [10] 0 0
Up to 6.5 years
Secondary outcome [11] 0 0
Change over time in free C5 concentration in crovalimab-treated participants
Assessment method [11] 0 0
Timepoint [11] 0 0
Up to 6.5 years
Secondary outcome [12] 0 0
Observed Value in Reticulocyte Count (count/mL)
Assessment method [12] 0 0
Timepoint [12] 0 0
Up to 6.5 years
Secondary outcome [13] 0 0
Observed Value in Free Hemoglobin and Haptoglobin (mg/dL)
Assessment method [13] 0 0
Timepoint [13] 0 0
Up to 6.5 years
Secondary outcome [14] 0 0
Change in Reticulocyte Count (count/mL)
Assessment method [14] 0 0
Timepoint [14] 0 0
Baseline up to Week 25
Secondary outcome [15] 0 0
Change in Free Hemoglobin and Haptoglobin (mg/dL)
Assessment method [15] 0 0
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 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).
Minimum age
No limit
Maximum age
No limit
Sex
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.
* 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 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
8/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2028
Actual
Sample size
Target
Accrual to date
Final
204
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Ciudad Autonoma Buenos Aires
Country [2] 0 0
Brazil
State/province [2] 0 0
Paraná
Country [3] 0 0
Brazil
State/province [3] 0 0
São Paulo
Country [4] 0 0
China
State/province [4] 0 0
Beijing
Country [5] 0 0
China
State/province [5] 0 0
Guangzhou
Country [6] 0 0
China
State/province [6] 0 0
Hangzhou City
Country [7] 0 0
China
State/province [7] 0 0
Nanjing
Country [8] 0 0
China
State/province [8] 0 0
Nantong City
Country [9] 0 0
China
State/province [9] 0 0
Shanghai
Country [10] 0 0
China
State/province [10] 0 0
Wuhan City
Country [11] 0 0
France
State/province [11] 0 0
Lille cedex
Country [12] 0 0
France
State/province [12] 0 0
Pierre-Bénite
Country [13] 0 0
Germany
State/province [13] 0 0
Essen
Country [14] 0 0
Germany
State/province [14] 0 0
Ulm
Country [15] 0 0
Greece
State/province [15] 0 0
Thessaloniki
Country [16] 0 0
Japan
State/province [16] 0 0
Hokkaido
Country [17] 0 0
Japan
State/province [17] 0 0
Ibaraki
Country [18] 0 0
Japan
State/province [18] 0 0
Tokyo
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Seoul
Country [20] 0 0
Lithuania
State/province [20] 0 0
Vilnius
Country [21] 0 0
Malaysia
State/province [21] 0 0
Perak
Country [22] 0 0
Malaysia
State/province [22] 0 0
Selangor
Country [23] 0 0
Mexico
State/province [23] 0 0
Mexico CITY (federal District)
Country [24] 0 0
Mexico
State/province [24] 0 0
Nuevo LEON
Country [25] 0 0
Netherlands
State/province [25] 0 0
Amsterdam
Country [26] 0 0
Philippines
State/province [26] 0 0
Lipa City
Country [27] 0 0
Philippines
State/province [27] 0 0
Manila
Country [28] 0 0
Philippines
State/province [28] 0 0
Quezon
Country [29] 0 0
Poland
State/province [29] 0 0
Bydgoszcz
Country [30] 0 0
Poland
State/province [30] 0 0
Gdansk
Country [31] 0 0
Poland
State/province [31] 0 0
Lublin
Country [32] 0 0
Poland
State/province [32] 0 0
Skórzewo
Country [33] 0 0
Poland
State/province [33] 0 0
Warszawa
Country [34] 0 0
Portugal
State/province [34] 0 0
Aveiro
Country [35] 0 0
Portugal
State/province [35] 0 0
Lisboa
Country [36] 0 0
Portugal
State/province [36] 0 0
Porto
Country [37] 0 0
Romania
State/province [37] 0 0
Bucuresti
Country [38] 0 0
Romania
State/province [38] 0 0
Craiova
Country [39] 0 0
Singapore
State/province [39] 0 0
Singapore
Country [40] 0 0
Spain
State/province [40] 0 0
Albacete
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
LAS Palmas
Country [43] 0 0
Spain
State/province [43] 0 0
Caceres
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Spain
State/province [45] 0 0
Salamanca
Country [46] 0 0
Taiwan
State/province [46] 0 0
Kaohisung
Country [47] 0 0
Taiwan
State/province [47] 0 0
Taipei
Country [48] 0 0
Thailand
State/province [48] 0 0
Bangkok
Country [49] 0 0
Thailand
State/province [49] 0 0
Chiang Mai
Country [50] 0 0
Thailand
State/province [50] 0 0
Pathum Wan
Country [51] 0 0
Turkey
State/province [51] 0 0
Samsun
Country [52] 0 0
Ukraine
State/province [52] 0 0
KIEV Governorate
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Leeds
Country [54] 0 0
United Kingdom
State/province [54] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
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/NCT04434092