This study aims to evaluate the efficacy and safety of crovalimab in adult and adolescent participants with aHUS.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
83
Crovalimab will be administered at a dose of 1000 milligrams (mg) intravenous (IV) (for participants with body weight at least 40 (\>=) and up to 100 kilograms (kg) or 1500 mg IV (for participants with body weight \>=100kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, it will be administered at a dose of 340 mg subcutaneously (SC). On Week 5 and every 4 weeks (Q4W) thereafter, it will be administered at a dose of 680 mg SC (for participants with body weight \>= 40kg to \<100kg) or 1020 mg SC (for participants with body weight \>=100kg).
Percentage of Participants with Complete Thormbotic Microangiopathy Response (cTMAr)
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 from Baseline in Estimated Glomerular Filtration Rate (eGFR)
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
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Observed Value in Platelet Count
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Observed Value in Lactate Dehydrogenase (LDH)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Observed Value in Hemoglobin
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Change from Baseline in Platelet Count
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Change from Baseline in Lactate Dehydrogenase (LDH)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Change from Baseline in Hemoglobin
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
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Univ of CA San Francisco
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Emory Children's Center
Atlanta, Georgia, United States
Washington University
St Louis, Missouri, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
UT Health Science Center
San Antonio, Texas, United States
UZ Leuven Gasthuisberg
Leuven, Belgium
Santa Casa de Misericordia
Belo Horizonte, Minas Gerais, Brazil
UPECLIN Hospital das Clinicas da Faculdade de Medicina de Botucatu
Botucatu, São Paulo, Brazil
...and 33 more locations
Mean Change From Baseline in Fatigue (in Adult Participants only)
Assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire. The FACIT-Fatigue (version 4) assesses self-reported fatigue and its impact upon daily activities and function. It consists of 13 items that assess fatigue using a 7-day recall period. Items are scored on a 0 (not at all) to 4 (very much) response scale. Relevant items are reverse scored and all items are summed to create total scores ranging from 0 \[worse score\] to 52 \[better score\].
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Percentage of Participants with Platelet Count >= Lower Limits of Normal (LLN) (Naive Cohort only)
Time frame: Baseline up to Week 25 (after 24 weeks on treatment)
Percentage of Participants with Normalization of LDH (i.e. =< Upper Limit of 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 cTMAr (Naive Cohort only)
Time frame: Up to 8 years
Duration of cTMAr (Naive Cohort only)
Time frame: Up to 8 years
Percentage of Participants with Ongoing cTMAr (Naive Cohort only)
Time frame: At Week 25
Percentage of Participants with Maintained Thrombotic Microangiopathy Control (mTMAc) (Switch Cohort only)
Time frame: Baseline up to 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
Number of Participants with 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 Those Participants who Switched to Crovalimab Treatment From Eculizumab Treatment or Ravulizumab Treatment
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