A Study Evaluating The Safety, Pharmacokinetics, and Efficacy Of Crovalimab Versus Eculizumab In Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Registration Number
- NCT04432584
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 190
Inclusion Criteria:<br><br> - Body weight >= 40 kg at screening.<br><br> - Treated with eculizumab or ravulizumab for PNH for at least 3 months prior to Day 1.<br><br> - Lactate Dehydrogenase Levels =< 2x the upper limit of normal (ULN) at screening.<br><br> - Willingness and ability to comply with all study visits and procedures.<br><br> - Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry.<br><br> - Vaccination against Neisseria meningitidis serotypes A, C, W, and Y < 3 years prior<br> to initiation of study treatment; or, if not previously done, vaccination<br> administered no later than one week after the first drug administration.<br><br> - Women of childbearing potential: agreement to remain abstinent (refrain from<br> heterosexual intercourse) or use contraception during the treatment period and for<br> 10.5 months after the final dose of crovalimab or for 3 months after the final dose<br> of eculizumab (or longer if required by the local product label).<br><br>Exclusion Criteria:<br><br> - History of allogeneic bone marrow transplantation.<br><br> - History of myelodysplastic syndrome with Revised International Prognostic Scoring<br> System (IPSS-R) prognostic risk categories of intermediate, high and very high.<br><br> - Pregnant or breastfeeding, or intending to become pregnant during the study, within<br> 10.5 months after the final dose of crovalimab, or 3 months after the final dose of<br> eculizumab (or longer if required by the local product label).<br><br> - Participation in another interventional treatment study with an investigational<br> agent or use of any experimental therapy within 28 days of screening or within 5<br> half-lives of that investigational product, whichever was greater: participants<br> enrolled in an eculizumab or ravulizumab interventional study are eligible provided<br> they fulfill eligibility (e.g., are willing and able to comply with the study<br> assessments) and stop their participation in current trial before<br> randomisation/enrolment.<br><br> - Positive for Active Hepatitis B and C infection (HBV/HCV).<br><br> - Concurrent disease, treatment, procedure, or surgery or abnormality in clinical<br> laboratory tests that could interfere with the conduct of the study, may pose any<br> additional risk for the participant, or would, in the opinion of the investigator,<br> preclude the participant's safe participation in and completion of the study.<br><br> - History of or ongoing cryoglobulinemia at screening.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Percentage of Participants with Adverse Events (AEs) and by Severity;Percentage of Participants with Injection- Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis);Percentage of Participants with Adverse Events (AEs) Leading to Study Drug Discontinuation;Percentage of Participants with Clinical Manifestations of Drug-Target-Drug Complex (DTDC) Formation Amongst Those Participants who Switched to Crovalimab Treatment from Eculizumab Treatment or Ravulizumab Treatment
- Secondary Outcome Measures
Name Time Method Serum Concentrations of Crovalimab or Eculizumab Over Time;Serum Concentrations of Ravulizumab at the time of Crovalimab Initiation;Percentage of Participants with Anti-Crovalimab Antibodies;Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time;Change Over Time in Free C5 Concentration in Crovalimab-Treated Participants;Observed Value in Reticulocyte Count (count/mL);Observed Value in Free Hemoglobin and Haptoglobin (mg/dL);Change in Reticulocyte Count (count/mL);Absolute Change in Free Hemoglobin and Haptoglobin (mg/dL)