A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition (COMMODORE 3)
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|ClinicalTrials.gov Identifier: NCT04654468|
Recruitment Status : Active, not recruiting
First Posted : December 4, 2020
Last Update Posted : September 13, 2021
|Condition or disease||Intervention/treatment||Phase|
|Paroxysmal Nocturnal Hemoglobinuria||Drug: Crovalimab||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||51 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase III, Multicenter, Single Arm Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition|
|Actual Study Start Date :||March 17, 2021|
|Estimated Primary Completion Date :||December 26, 2022|
|Estimated Study Completion Date :||December 26, 2022|
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.
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.
- Mean Percentage of Participants with Hemolysis Control [ Time Frame: Week 5 through Week 25 ]Measured by LDH =< 1.5 x ULN (as measured at the central laboratory).
- Change from Baseline to Week 25 in Percentage of Participants who achieve Transfusion Avoidance (TA) [ Time Frame: Baseline, Week 25 ]TA is defined as participants who are packed Red Blood Cell (pRBC) transfusion-free and do not require transfusion per protocol-specified guidelines.
- Percentage of Participants with Breakthrough Hemolysis (BTH) [ Time Frame: Baseline through Week 25 ]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.
- Percentage of Participants with Stabilization of Hemoglobin [ Time Frame: Baseline through Week 25 ]Stabilized hemoglobin is defined as avoidance of a >= 2 g/dL decrease in hemoglobin level from baseline, in the absence of transfusion.
- Mean Change in Fatigue [ Time Frame: Baseline up to Week 25 ]Assessed by the FACIT-Fatigue Questionnaire (for adults aged >= 18 years).
- Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 2 years ]Determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.
- Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including meningococcal meningitis) [ Time Frame: Up to 2 years ]
- Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation [ Time Frame: Up to 2 years ]
- Trough Serum Concentration of Crovalimab over time [ Time Frame: Up to 2 years ]
- Serum Concentrations of Crovalimab at specified timepoints [ Time Frame: Up to 2 years ]
- Percentage of Participants with Anti-Crovalimab Antibodies [ Time Frame: Up to 2 years ]
- Change over time in PD biomarkers including complement activity [ Time Frame: Up to 2 years ]Assessed by a Liposome Immunoassay (LIA)
- Change over time in total and free C5 concentration [ Time Frame: Up to 2 years ]
- Observed Value in Reticulocyte Count (count/mL) [ Time Frame: Up to 2 years ]
- Observed Value in Free Hemoglobin and Haptoglobin (mg/dL) [ Time Frame: Up to 2 years ]
- Change in Reticulocyte Count (count/mL) [ Time Frame: Baseline up to Week 25 ]
- Change in Free Hemoglobin and Haptoglobin (mg/dL) [ Time Frame: Baseline up to Week 25 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04654468
|Peking University People's Hospital|
|Beijing, China, 100044|
|The First Hospital of Jilin University|
|Changchun City, China, 130021|
|West China Hospital, Sichuan University|
|Chengdu, China, 610041|
|Guangdong General Hospital|
|Guangzhou, China, 510080|
|Institute of Hematology and Hospital of Blood Disease|
|Tianjin City, China, 300020|
|Tianjin Medical University General Hospital|
|Tianjin, China, 300052|
|Union Hospital Tongji Medical College Huazhong University of Science and Technology|
|Wuhan City, China, 430023|
|Study Director:||Clinical Trials||Hoffmann-La Roche|