A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition

NCT04654468 | Active Not Recruiting Phase 3 Results FDA Drug

• 1 other identifier: YO42311
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 4

Brief Summary

This study will enroll participants aged 12 years or older with a body weight ≥ 40 kilograms (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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Outcome Measures

Primary Outcomes (2)

• Mean Percentage of Participants With Hemolysis Control

  A Generalized Estimating Equation (GEE) was used to estimate the population-average percentage of the participants with hemolysis control (measured by lactate dehydrogenase (LDH) ≤1.5 x upper limit of normal (ULN)) from Week 5 to Week 25 taking account of the intra-patient and inter-patient correlation between LDH control statuses across visits. The dependent variable was the binary indicator for hemolysis control. Independent variables are categorical effects of visits, continuous baseline LDH.

  From Week 5 up to Week 25

• Difference in Percentage of Participants With Transfusion Avoidance (TA) From Baseline Through Week 25 and Within 24 Weeks Prior to Screening

  TA was defined as participants who were packed red blood cell (pRBC) transfusion-free and did not require transfusion per protocol-specified guidelines. TA within 24 weeks prior to screening was based on the pRBC transfusion history in the medical records. Reported in this outcome measure is the difference in the percentage of participants between "baseline through Week 25" and "within 24 weeks prior to screening". 95% Confidence Interval (CI) for the difference between the percentage of participants with transfusion avoidance between Pre-screening and Post-baseline is calculated using the Newcombe method. Screening= Day -28 to Day -1 and Baseline= Day 1.

  24 Weeks Prior to Screening, Baseline to Week 25

Secondary Outcomes (17)

• Percentage of Participants With Breakthrough Hemolysis (BTH)

  Baseline, Week 25

• Percentage of Participants With Stabilized Hemoglobin

  Baseline, Week 25

• Change From Baseline in Fatigue in Adults Aged >=18 Years

  Baseline, Week 2, Week 5, Week 9, Week 17, Week 25

• Percentage of Participants With Adverse Events (AEs)

  Up to 7 years

• Percentage of Participants With Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, and Infections (Including Meningococcal Meningitis)

  Up to 7 years

Study Arms (1)

Crovalimab

EXPERIMENTAL

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

Interventions

Crovalimab DRUG

Crovalimab will be administered at a dose of 1000 milligrams (mg) IV (for participants with body weight between 40 and 100 kg) or 1500 mg IV (for participants with body weight ≥ 100 kg) 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 100 kg) or 1020 mg SC (for participants with body weight ≥ 100 kg). Dosing schedule will be as described above.

Crovalimab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Levels ≥ 2x the 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 PNH-related signs or symptoms within 3 months of screening
• Vaccination against Neisseria meningitidis serotypes A, C, W, and Y \< 3 years prior to initiation of study treatment (Day 1)
• 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 46 weeks (approximately 10.5 months) after the final dose of crovalimab
• Platelet count ≥30,000 per cubic millimeter (mm\^3) at screening
• ANC \> 500/microlitres (μl) at screening

You may not qualify if:

• 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 cluster of differentiation 4 (CD4) count \< 200 cells/µl within 24 weeks prior to screening
• Infection requiring hospitalization or treatment with 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 intending to become pregnant during the study or within 46 weeks (10.5 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (4)

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Institute of Hematology and Hospital of Blood Disease

Tianjin, 300020, China

Location

Tianjin Medical University General Hospital

Tianjin, 300052, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430022, China

Location

Related Publications (2)

• Roth A, Fu R, He G, Alzahrani H, Chou SC, Hicheri Y, Kazmierczak M, Recova VL, Uchiyama M, Vladareanu AM, Beveridge L, Buatois S, Buri M, Compagno N, Shi D, Balachandran N, Sreckovic S, Scheinberg P. Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH): Pooled Results From the Phase 3 COMMODORE Studies. Eur J Haematol. 2025 Feb;114(2):373-382. doi: 10.1111/ejh.14339. Epub 2024 Nov 13.

  PMID: 39535306 DERIVED

• Liu H, Xia L, Weng J, Zhang F, He C, Gao S, Jia J, Chang AC, Lundberg P, Shi J, Sima CS, Sostelly A, Sreckovic S, Xiao Z, Zhang Z, Fu R. Efficacy and safety of the C5 inhibitor crovalimab in complement inhibitor-naive patients with PNH (COMMODORE 3): A multicenter, Phase 3, single-arm study. Am J Hematol. 2023 Sep;98(9):1407-1414. doi: 10.1002/ajh.26998. Epub 2023 Jul 8.

  PMID: 37421604 DERIVED

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: December 4, 2020
• Study Start: March 17, 2021
• Primary Completion: February 10, 2022
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 11, 2026
• Results First Posted: June 5, 2023

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

CN (4)