A Study to Evaluate the Efficacy and Safety of Crovalimab versus Eculizumab in Adult and Adolescent Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated with Complement Inhibitors.
- Conditions
- PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)MedDRA version: 21.1Level: PTClassification code 10034042Term: Paroxysmal nocturnal haemoglobinuriaSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-000597-26-HU
- Lead Sponsor
- F.Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 250
General Inclusion Criteria (All Patients)
- Body weight >= 40 kg
- Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry evaluation of WBCs,
- Vaccination against Neisseria meningitidis < 3 years prior to initiation of study treatment, in accordance with most current local guidelines or standard-of-care as applicable in patients with complement deficiency
- For women of childbearing potential: agreement to remain abstinent or use contraception
For Patients in Randomized Arms (Arm A and B)
- Age >= 18 years
- Documented treatment with eculizumab according to the approved dosing recommended for PNH and completion of a minimum of 24 weeks of treatment prior to Day 1
- Lactate dehydrogenase (LDH) <= 1.5 × ULN at screening
For Patients in Descriptive Arm (Arm C)
- Age 12-18 old, currently treated with eculizumab OR
- Age >= 12 years old currently treated with ravulizumab OR
- Age >= 12 years old currently treated with eculizumab at higher-than-approved doses OR
- Patients with known C5 polymorphism and poorly controlled hemolysis by eculizumab or ravulizumab
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 195
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
- Major Adverse Vascular Event within 6 months prior to first drug administration (Day 1)
- Platelet count < 30000/mm3 at screening
- ANC < 500/microlitre at screening
- History of allogeneic bone marrow transplantation,
- Neisseria meningitidis infection within 6 months prior to screening and up to first study drug administration
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 6 months after the final dose of study treatment
- 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 HCV 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 based on the non-inferiority assessment<br>• To evaluate the safety and tolerability of crovalimab compared to eculizumab<br>• To characterize the crovalimab, eculizumab, and ravulizumab pharmacokinetics profile<br>• To evaluate the immune response to crovalimab<br>• To identify and/or evaluate biomarkers that can potentially provide evidence of crovalimab, eculizumab, and ravulizumab activity<br><br>;Primary end point(s): Mean percent change in LDH level;Timepoint(s) of evaluation of this end point: From Baseline to Week 25
- Secondary Outcome Measures
Name Time Method