A Study to Evaluate the Efficacy and Safety of Crovalimab versus Eculizumab in Adult and Adolescent Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) not previously Treated with Complement Inhibitors

Phase 1

• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH); MedDRA version: 21.1Level: LLTClassification code 10055629Term: Paroxysmal nocturnal hemoglobinuriaSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2019-004931-21-PT
• Lead Sponsor: F. Hoffman-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-10-28
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

- Body weight >= 40 kg
- Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry evaluation of WBCs
- LDH level >=2 x 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. Vaccination against serotype B should be administered in accordance with the most current local guidelines or SOC, as applicable in patients with complement deficiency. If not previously administered or no longer current, vaccination must be completed no later than one week after the first study drug administration. Vaccination currency with vaccination against serotypes A, C, W, Y and B should be maintained throughout the study, according to local guidelines or standard-of-care as applicable in patients with complement deficiency. In the absence of clear local guidelines for Neisseria meningitidis, the Advisory Committee on Immunization Practices 2020 Guidelines are recommended.
- Platelet count >= 30,000/mm*3 at screening without transfusion support within 7 days of lab testing.
- ANC > 500/micro L at screening
- For female patients of childbearing potential: agreement to remain abstinent or use contraception

Additional Inclusion Criteria for Patients in the Randomized Arms
-Age >=18 years
Additional Inclusion Criteria for Patients in the Descriptive Arm
- Age < 18 years
Are the trial subjects under 18? yes
Number of subjects for this age range: 3
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 37

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 or within 46 weeks (approximately 10.5 months) after the final dose of crovalimab, or 3
months after final dose of eculizumab (or longer if required by the local
product label)
- 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 patient, or would, in the
opinion of the Investigator, preclude the patient's safe participation in
and completion of the study
- Splenectomy <= 6 months prior to screening
- Positive for hepatitis B surface antigen at screening
- Positive for hepatitis C virus antibody at screening (confirmed by
detectable viral RNA)
- History of or ongoing cryoglobulinemia at screening

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of crovalimab compared to eculizumab;Secondary Objective: • To evaluate the efficacy of crovalimab compared with eculizumab<br>• To evaluate the overall safety and tolerability of crovalimab compared to eculizumab<br>• To evaluate the pharmacokinetics of crovalimab and eculizumab <br>• To evaluate the immune response to crovalimab<br>• To identify and/or evaluate biomarkers that can potentially provide evidence of crovalimab and eculizumab activity<br><br>;Primary end point(s): 1. Proportion of patients who achieve transfusion avoidance <br>2. Proportion of patients with hemolysis control, measured by LDH <=1.5×ULN<br>;Timepoint(s) of evaluation of this end point: 1. From Baseline to Week 25<br>2. From Week 5 to Week 25