A Study to Evaluate the Efficacy and Safety of Crovalimab versus Eculizumab in 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-PT
- 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, or, if not previously done, vaccination administered
no later than one week after the first drug administration. Vaccination
currency should be maintained throughout the study in accordance with
most current local guidelines or standard-of-care as applicable in
patients with complement deficiency
- Platelet count >= 30,000/mm*3 at screening without transfusion
support within 7 days of lab testing
- ANC > 500/micro L at screening
- 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 <18 old, currently treated with eculizumab OR
- Currently treated with ravulizumab OR
- 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: 4
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 196
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)
- History of allogeneic bone marrow transplantation
- 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 6 months after the final dose of crovalimab, or 3
months after the 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 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): Percent change from baseline in LDH level averaged over Weeks 21, 23,<br>and 25 LDH measurements;Timepoint(s) of evaluation of this end point: From Baseline to Weeks 21, 23, 25
- Secondary Outcome Measures
Name Time Method