A PHASE III, RANDOMIZED, OPEN-LABEL, ACTIVE-CONTROLLED, MULTICENTER STUDY EVALUATING SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS, AND EFFICACY OF CROVALIMAB VERSUS ECULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) CURRENTLY TREATED WITH COMPLEMENT INHIBITORS
- Conditions
- Paroxysmal nocturnal hemoglobinuriaPNH10038158
- Registration Number
- NL-OMON54448
- Lead Sponsor
- F. Hoffmann- La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 4
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
standardofcare
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
- 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) prognosticrisk 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>1. Incidence and severity of adverse events<br /><br>2. Change from baseline in targeted vital signs<br /><br>3. Change from baseline in targeted clinical laboratory test results<br /><br>4. Incidence and severity of injection-site reactions, infusion-related<br /><br>reactions, hypersensitivity, and infections<br /><br>5. Incidence of adverse events leading to study drug discontinuation<br /><br>6. Incidence and severity of clinical manifestations of drug-target-drug<br /><br>complex formation in patients who switched to crovalimab treatment<br /><br>from eculizumab or ravulizumab treatment</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. Serum concentration of crovalimab or eculizumab<br /><br>2. Serum concentration of ravulizumab<br /><br>3. Prevalence and incidence of anti-drug antibodies (ADAs) to<br /><br>crovalimab<br /><br>4. Change over time in pharmacodynamic biomarkers<br /><br>5. Change over time in free C5 concentration in crovalimab-treated<br /><br>patients<br /><br>6. Observed value and absolute change in parameters reflecting<br /><br>hemolysis<br /><br>7. Percent change from baseline in LDH level averaged over Weeks 21,<br /><br>23, and 25 LDH measurements<br /><br>8. Proportion of patients with transfusion avoidance<br /><br>9. Proportion of patients with breakthrough hemolysis<br /><br>10. Proportion of patients with stabilization of hemoglobin<br /><br>11. Mean change in fatigue as assessed through use of the Functional<br /><br>Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale</p><br>