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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
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study will enrol participants aged 12 years or older with a body weight >= 40 kg diagnosed with PNH who have not been previously treated with complement inhibitor therapy. Approximately 50 participants will be treated with Crovalimab for at least 24 weeks.

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria Drug: Crovalimab Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
Experimental: 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.
Drug: 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.




Primary Outcome Measures :
  1. 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).

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Mean Change in Fatigue [ Time Frame: Baseline up to Week 25 ]
    Assessed by the FACIT-Fatigue Questionnaire (for adults aged >= 18 years).

  4. 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.

  5. Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including meningococcal meningitis) [ Time Frame: Up to 2 years ]
  6. Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation [ Time Frame: Up to 2 years ]
  7. Trough Serum Concentration of Crovalimab over time [ Time Frame: Up to 2 years ]
  8. Serum Concentrations of Crovalimab at specified timepoints [ Time Frame: Up to 2 years ]
  9. Percentage of Participants with Anti-Crovalimab Antibodies [ Time Frame: Up to 2 years ]
  10. Change over time in PD biomarkers including complement activity [ Time Frame: Up to 2 years ]
    Assessed by a Liposome Immunoassay (LIA)

  11. Change over time in total and free C5 concentration [ Time Frame: Up to 2 years ]
  12. Observed Value in Reticulocyte Count (count/mL) [ Time Frame: Up to 2 years ]
  13. Observed Value in Free Hemoglobin and Haptoglobin (mg/dL) [ Time Frame: Up to 2 years ]
  14. Change in Reticulocyte Count (count/mL) [ Time Frame: Baseline up to Week 25 ]
  15. Change in Free Hemoglobin and Haptoglobin (mg/dL) [ Time Frame: Baseline up to Week 25 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  • Lactate Dehydrogenase Levels >= 2x the upper limit of normal (ULN) at screening.
  • Participants who have at least four transfusions during 12 months prior to screening (documented in the medical record).
  • Presence of one or more of the following PNH-related signs or symptoms within 3 months of screening.
  • Vaccination against Neisseria meningitidis < 3 years prior to initiation of study treatment or within 7 days after the first drug administration.
  • Vaccination against Haemophilius influenzae type B and Streptococcus pneumonia according to national vaccination recommendations.
  • For participants receiving other therapies (e.g., immunosuppressants, corticosteroids): stable dose for >= 28 days prior to screening and up to the first drug administration.
  • Adequate hepatic and renal function.
  • 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.

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 drug administration.
  • Known or suspected immune or hereditary complement deficiency.
  • Known HIV infection with CD4 count < 200 cells/µl within 24 weeks prior to screening.
  • Infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 28 days prior to screening and up to the first drug administration, or oral antibiotics within 14 days prior to screening and up to the first drug administration.
  • Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration.
  • Presence of fever (>= 38˚C) within 7 days before the first drug administration.
  • Splenectomy < 6 months before screening.
  • History of malignancy within 5 years prior to screening and up to the first drug administration.
  • 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 is greater.

Information from the National Library of Medicine

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


Locations
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China
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
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04654468    
Other Study ID Numbers: YO42311
First Posted: December 4, 2020    Key Record Dates
Last Update Posted: September 13, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Hemoglobinuria
Hemoglobinuria, Paroxysmal
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases