This study aims to evaluate the efficacy and safety of crovalimab in pediatric participants with aHUS.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Crovalimab will be administered at a dose of 1000 mg intravenously (IV) (for participants weighing =\> 40 to \<100 kg) or 1500 mg IV (for participants weighing \>=100 kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, crovalimab will be administered at a dose of 340 mg subcutaneously (SC). On Week 5 and Q4W thereafter, it will be administered at a dose of 680 mg SC (for participants weighing =\> 40 to \<100 kg) or 1020 mg SC (for participants weighing \>=100 kg). Enrollment of participants weighing \<40 kg will be staggered using two weight-based dose confirmation groups (Group 1 participants weighing \>=20 kg to \<40 kg, followed by Group 2 participants weighing \>=5 kg to \<20 kg). All participants will receive an initial IV loading dose, which will be followed by SC dosing at either Q2W or Q4W intervals (depending on body weight), until study completion.
Children's Hospital Colorado
Aurora, Colorado, United States
University of Nebraska
Omaha, Nebraska, United States
Percentage of Participants with complete TMA response (cTMAr) (Naive Cohort only)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Change from Baseline in Dialysis Status
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Change in Estimated Glomerular Filtration Rate (eGFR) (Naive and Switch Cohorts)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Percentage of Participants with Change from Baseline in Chronic Kidney Disease (CKD) stage (Naive and Switch Cohorts)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Observed Value in Platelet Count (Naive and Switch Cohorts)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Observed Value in Lactate Dehydrogenase (LDH) (mg/dL) (Naive and Switch Cohorts)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Observed Value in Hemoglobin (mg/dL) (Naive and Switch Cohorts)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Change from Baseline in Platelet Count (Naive and Switch Cohorts)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Change from Baseline in Lactate Dehydrogenase (LDH) (mg/dL) (Naive and Switch Cohorts)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
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Hackensack University Medical Center
Hackensack, New Jersey, United States
UZ Gent
Ghent, Belgium
UZ Leuven Gasthuisberg
Leuven, Belgium
Inst. Da Criança- Faculdade de Medicina Usp
São Paulo, São Paulo, Brazil
CHU Sainte-Justine
Montreal, Quebec, Canada
Peking University First Hospital
Beijing, China
Beijing Children's Hospital, Capital Medical University
Beijing, China
The children's hospital , Zhejiang university school of medicine
Hangzhou, China
...and 10 more locations
Change from Baseline in Hemoglobin (mg/dL) (Naive and Switch Cohorts)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Percentage of Participants with Platelet Count >= LLN (Naive Cohort only)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Percentage of Participants with Normalisation of LDH (i.e., =< Upper Limit Normal (ULN)) (Naive Cohort only)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Percentage of Participants with >=25% decrease in Serum Creatinine (Naive Cohort only)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Time to complete TMA response (cTMAr) (Naive Cohort only)
Time frame: Up to 8 years
Duration of complete TMA response (cTMAr) (Naive Cohort only)
Time frame: Up to 8 years
Percentage of Participants with ongoing complete TMA response (cTMAr) (Naive Cohort only)
Time frame: At Week 25
Percentage of Participants with maintained TMA control (mTMAc) (Switch Cohort only)
Time frame: Baseline through Week 25 (after 24 weeks on treatment)
Percentage of Participants with Adverse Events (AEs)
Time frame: Up to 8 years
Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, Malignant Hypertension (including malignant renal hypertension) and Infections (including meningococcal meningitis)
Time frame: Up to 8 years
Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation
Time frame: Up to 8 years
Percentage of Participants with Clinical Manifestations of Drug-Target-Drug Complex (DTDC) formation amongst participants who switched to crovalimab treatment from eculizumab/ravulizumab treatment (Switch Cohort and switching Pretreated participants)
Time frame: Up to Week 25
Serum Concentrations of Crovalimab over time
Time frame: Up to 8 years
Prevalence of Anti-Crovalimab Antibodies at Baseline
Time frame: Baseline
Percentage of Participants with Anti-Crovalimab Antibodies
Time frame: Up to 8 years
Observed value of Pharmacodynamic Markers (CH50, Free/Total C5)
Time frame: Up to 8 years