A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, andefficacy of Crovalimab versus Eculizumab in Adult and Adolescent Patientswith Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated withComplement 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-PL
- Lead Sponsor
- F.Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 190
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 serotypes A, C, W, and Y <
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 standardof-
care as applicable in patients with complement deficiency
- Vaccination against Haemophilus influenzae type B and Streptococcus
pneumoniae according to national vaccination recommendations
- 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
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 Non Randomized 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
- Adult patients currently treated with approved doses of eculizumab LDH <= 1.5 × ULN at screening
Are the trial subjects under 18? yes
Number of subjects for this age range: 3
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 152
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35
- 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 46 weeks (approximately 10.5 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
- Secondary Outcome Measures
Name Time Method