Paroxysmal Nocturnal Hemoglobinuria
Conditions
Brief summary
A study designed to evaluate the safety of crovalimab with eculizumab in participants with PNH currently treated with complement inhibitors. This study will enroll approximately 190 participants.
Interventions
DRUGCrovalimab
Dosing depends on body weight. Participants will be dosed as follows: * 5 kg to \< 12 kg: 100 mg IV on Week 1 Day 1 (W1D1); 85 mg SC on Week 1 Day 2 (W1D2) and Q2W from Week 3 until end of study * 12 kg to \< 20 kg: 200 mg IV on W1D1; 85 mg SC on W1D2, Weeks 2, 3 and 4; 170 mg SC, Q2W from Week 5 until end of study * 20 kg to \< 30 kg: 300 mg IV on W1D1; 85 mg SC on W1D2, Weeks 2, 3 and 4; 340 mg SC, Q4W from Week 5 until end of study * 30 kg to \< 40 kg: 400 mg IV on W1D1; 170 mg SC on W1D2, Weeks 2, 3 and 4; 510 mg SC, Q4W from Week 5 until end of study * 40 kg to \< 100 kg: 1000 mg IV on W1D1; 340 mg SC W1D2, Weeks 2, 3 and 4; 680 mg SC, Q4W from Week 5 until end of study * 100 kg: 1500 mg IV on W1D1; 340 mg SC W1D2, Weeks 2, 3 and 4; 1020 mg SC, Q4W from Week 5 until end of study.
DRUGEculizumab
Eculizumab will be administered at a dose of 900 mg Q2W, as per the dosing schedule described above.
Sponsors
Hoffmann-La Roche
Chugai Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Body weight ≥ 40 kg at screening (pediatric participants with body weight \< 40 kg) * Treated with eculizumab or ravulizumab for PNH for at least 3 months prior to Day 1 * Lactate Dehydrogenase Levels ≤ 2x the upper limit of normal (ULN) at screening * Willingness and ability to comply with all study visits and procedures * Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry * 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 * Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 10.5 months after the final dose of crovalimab or for 3 months after the final dose of eculizumab (or longer if required by the local product label)
Exclusion criteria
* History of allogeneic bone marrow transplantation * 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, within 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) * Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within 5 half-lives of that investigational product, whichever was greater: participants enrolled in an eculizumab or ravulizumab interventional study are eligible provided they fulfill eligibility (e.g., are willing and able to comply with the study assessments) and stop their participation in current trial before randomisation/enrolment * Positive for Active Hepatitis B and C infection (HBV/HCV) * 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 participant, or would, in the opinion of the investigator, preclude the participant's safe participation in and completion of the study * History of or ongoing cryoglobulinemia at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) and by Severity | Up to approximately 6 years | Severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5 (CTCAE v5). |
| Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis) | Up to approximately 6 years | — |
| Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation | Up to approximately 6 years | — |
| 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 | Up to approximately 6 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time | Up to approximately 6 years |
| Observed Value in Reticulocyte Count (count/milliliters [mL]) | Up to approximately 6 years |
| Observed Value in Free Hemoglobin and Haptoglobin (milligrams per deciliter [mg/dL]) | Up to approximately 6 years |
| Absolute Change From Baseline in Reticulocyte Count (count/mL) | Baseline up to Week 25 |
| Change Over Time in Free C5 Concentration in Crovalimab-treated Participants | Up to approximately 6 years |
| Absolute Change From Baseline in Free Hemoglobin and Haptoglobin (mg/dL) | Baseline up to Week 25 |
| Serum Concentrations of Crovalimab or Eculizumab Over Time | Up to approximately 6 years |
| Serum Concentrations of Ravulizumab at the Time of Crovalimab Initiation | Baseline |
| Percentage of Participants With Anti-crovalimab Antibodies | Up to approximately 6 years |
Countries
Belgium, Brazil, Czechia, Estonia, France, Germany, Greece, Hong Kong, Hungary, Ireland, Italy, Japan, Netherlands, Poland, Portugal, Saudi Arabia, Singapore, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed