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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
Date last updated
1/05/2025
Titles & IDs
Public title
A Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors
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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
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Secondary ID [1]
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2019-004931-21
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Secondary ID [2]
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BO42162
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Universal Trial Number (UTN)
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Trial acronym
COMMODORE 2
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria
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Condition category
Condition code
Blood
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Haematological diseases
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Intervention/exposure
Study type
Interventional
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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 kilograms \[kg\]) or 1500 mg (for participants with body weight = 100 kg), 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 100 kg) or 1020 mg (for participants with body weight = 100 kg) 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) - Participants with a body weight = 5 to \<12 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 as specified in the respective arm.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percentage of Participants Who Achieve Transfusion Avoidance (TA)
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Assessment method [1]
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TA is defined as participants who are packed red blood cell (pRBC) transfusion-free and do not require transfusion per protocol-specified guidelines.
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Timepoint [1]
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Baseline through Week 25
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Primary outcome [2]
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Percentage of Participants With Hemolysis Control
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Assessment method [2]
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Measured by lactate dehydrogenase (LDH) = 1.5 x upper limit of normal (ULN) (as measured at the central laboratory).
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Timepoint [2]
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Week 5 through Week 25
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Secondary outcome [1]
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Percentage of Participants With Breakthrough Hemolysis (BTH)
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Assessment method [1]
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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 \[hemoglobin \< 10 grams per deciliter (g/dL)\], 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.
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Timepoint [1]
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Baseline through Week 25
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Secondary outcome [2]
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Percentage of Participants With Stabilization of Hemoglobin
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Assessment method [2]
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Stabilized hemoglobin is defined as avoidance of a = 2 g/dL decrease in hemoglobin level from baseline, in the absence of transfusion.
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Timepoint [2]
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Baseline through Week 25
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Secondary outcome [3]
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Mean Change in Fatigue
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Assessment method [3]
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Assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire.
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Timepoint [3]
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Baseline up to Week 25
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Secondary outcome [4]
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Percentage of Participants With Adverse Events (AEs)
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Assessment method [4]
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Determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.
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Timepoint [4]
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Up to 6 years
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Secondary outcome [5]
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Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (Including Meningococcal Meningitis)
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Assessment method [5]
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Timepoint [5]
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Up to 6 years
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Secondary outcome [6]
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Percentage of Participants With AEs Leading to Study Drug Discontinuation
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Assessment method [6]
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Timepoint [6]
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Up to 6 years
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Secondary outcome [7]
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Percentage of Participants With Clinical Manifestations of Drug-target-drug Complex (DTDC) Formation Amongst Those Participants Who Switched to Crovalimab Treatment From Eculizumab Treatment
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Assessment method [7]
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Timepoint [7]
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Up to 6 years
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Secondary outcome [8]
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Serum Concentrations of Crovalimab and Eculizumab Over Time
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Assessment method [8]
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Timepoint [8]
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Up to 6 years
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Secondary outcome [9]
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Percentage of Participants With Anti-crovalimab Antibodies
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Assessment method [9]
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Timepoint [9]
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Up to 6 years
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Secondary outcome [10]
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Change in Pharmacodynamic (PD) Biomarkers Including Complement Activity (CH50) Over Time
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Assessment method [10]
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Assessed by a Liposome Immunoassay (LIA) and total C5 concentration.
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Timepoint [10]
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Up to 6 years
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Secondary outcome [11]
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Change Over Time in Free C5 Concentration in Crovalimab-treated Participants
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Assessment method [11]
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Timepoint [11]
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Up to 6 years
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Secondary outcome [12]
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Observed Value in Reticulocyte Count (count/milliliters [mL])
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Assessment method [12]
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Timepoint [12]
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Up to 6 years
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Secondary outcome [13]
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Observed Value in Free Hemoglobin and Haptoglobin (milligrams per deciliter [mg/dL])
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Assessment method [13]
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Timepoint [13]
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Up to 6 years
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Secondary outcome [14]
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Change From Baseline in Reticulocyte Count (count/mL)
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Assessment method [14]
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Timepoint [14]
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Baseline up to Week 25
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Secondary outcome [15]
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Change From Baseline in Free Hemoglobin and Haptoglobin (mg/dL)
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Assessment method [15]
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Timepoint [15]
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Baseline up to Week 25
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Eligibility
Key inclusion criteria
* Body weight = 40 kg at screening (pediatric participants with body weight < 40 kg)
* 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)
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Minimum age
2
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
8/10/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
30/09/2027
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Actual
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Sample size
Target
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Accrual to date
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Final
204
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Recruitment in Australia
Recruitment state(s)
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Recruitment outside Australia
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Argentina
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Ciudad Autonoma Buenos Aires
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Brazil
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Paraná
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Brazil
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São Paulo
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China
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Beijing
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China
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Guangzhou
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China
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Hangzhou City
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China
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Nanjing
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China
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China
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China
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France
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Germany
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Essen
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Germany
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Ulm
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Japan
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Vilnius
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Perak
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Mexico
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Lipa City
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Manila
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Philippines
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Quezon
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Aveiro
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Bucuresti
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Barcelona
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LAS Palmas
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Caceres
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Kaohisung
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Taipei
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Bangkok
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Chiang Mai
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Thailand
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Pathum Wan
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Turkey
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Samsun
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Ukraine
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KIEV Governorate
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United Kingdom
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Leeds
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United Kingdom
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London
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Hoffmann-La Roche
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Address
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Other collaborator category [1]
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Commercial sector/industry
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Name [1]
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Chugai Pharmaceutical
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Ethics approval
Ethics application status
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Summary
Brief 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.
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Trial website
https://clinicaltrials.gov/study/NCT04434092
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Trial related presentations / publications
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Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed
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Contacts
Principal investigator
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Hoffmann-La Roche
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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
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