A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
Phase 3
Active, not recruiting
- Conditions
- Atypical Hemolytic Uremic Syndrome
- Interventions
- Registration Number
- NCT04861259
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study aims to evaluate the efficacy and safety of crovalimab in adult and adolescent participants with aHUS.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 83
Inclusion Criteria
- Body weight >= 40 kg at screening.
- Vaccination against Neisseria meningitidis serotypes A, C, W, and Y; vaccination against serotypes B, according to national vaccination recommendations.
- Vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae, according to national vaccination recommendations.
- For participants continuing to receive other therapies concomitantly with crovalimab (e.g., immunosuppressants, corticosteroids, mammalian target of rapamycin inhibitor (mTORi) , or calcineurin inhibitors): stable dose for >=28 days prior to screening and up to the first crovalimab administration.
- For female participants of childbearing potential: an agreement to remain abstinent or use contraception.
- Female participants of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of crovalimab.
- Participants with a prior kidney transplant are eligible if they have a known history of complement-mediated aHUS prior to the kidney transplant.
- Onset of initial TMA presentation within 28 days prior to the first dose of crovalimab (for Naive Cohort only).
- Documented treatment with either eculizumab or ravulizumab (for Switch Cohort only).
- Clinical evidence of response to a C5 inhibitor (for Switch Cohort only).
- Known C5 polymorphism (for C5 SNP Cohort only).
- Poorly controlled TMA following treatment with another C5 inhibitor (for C5 SNP Cohort only).
Exclusion Criteria
- TMA associated with non-aHUS related renal disease.
- Positive direct Coombs test.
- Chronic dialysis within 90 days prior to first crovalimab administration and/or end stage renal disease.
- Identified drug exposure-related TMA.
- Presence or history of a condition that could trigger TMA, such as malignancy, bone marrow or organ transplant (other than kidney transplant) or autoimmune disease.
- History of a kidney disease, other than aHUS.
- History of Neisseria meningitidis infection within 6 months of study enrollment.
- Known or suspected immune deficiency (e.g., history of frequent recurrent infections).
- Positive Human Immunodeficiency Virus (HIV) test.
- Active systemic bacterial, viral, or fungal infection within 14 days before first crovalimab administration
- Presence of fever (>= 38°C)
- Multi-system organ dysfunction or failure.
- Recent intravenous immunoglobulin (IVIg) treatment.
- Pregnant or breastfeeding or intending to become pregnant.
- Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within five half lives of that investigational product, whichever is greater.
- Recent use of tranexamic acid.
- Current or previous treatment with a complement inhibitor (for Naive Cohort only).
- First initiation of plasma exchange/plasma infusions (PE/PI) should not be more than 28 days prior to first crovalimab administration (for Naive Cohort only).
- Last PE/PI completed less than 2 hours prior to first crovalimab administration (for Naive Chorot only).
- Receiving PE/PI within 8 weeks of the first crovalimab administration (Switch Cohort only).
- Positive for active Hepatitis B and C infection (HBV/HCV) (for Switch Cohort and C5 SNP Cohort participants who recently received C5 inhibitor treatment).
- Cryoglobulinemia at screening (for Switch Cohort and C5 SNP Cohort participants who recently received C5 inhibitor treatment).
- Diagnosis of condition leading to non-aHUS TMA: Thrombotic Thrombocytopenic Purpura (TTP), Shiga Toxin producing Escherichia Coli (STEC)
- TMA, Pneumococcal HUS, TMA secondary to cobalamin C defect and TMA related to a known DGKE nephropathy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Crovalimab Crovalimab Participants will be enrolled in three cohorts: \[1\] Naive Cohort - participants who have not been previously treated with complement inhibitor therapy; \[2\] Switch Cohort - participants who switch to crovalimab from another Complement Component 5 (C5) inhibitor and \[3\] C5 Single Nucleotide Polymorphism (C5 inhibitor) Cohort - participants with documented C5 polymorphism.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Complete Thormbotic Microangiopathy Response (cTMAr) Baseline up to Week 25 (after 24 weeks on treatment)
- Secondary Outcome Measures
Name Time Method Change from Baseline in Dialysis Status Baseline up to Week 25 (after 24 weeks on treatment) Change from Baseline in Estimated Glomerular Filtration Rate (eGFR) Baseline up to Week 25 (after 24 weeks on treatment) Percentage of Participants with Change from Baseline in Chronic Kidney Disease (CKD) Stage Baseline up to Week 25 (after 24 weeks on treatment) Observed Value in Platelet Count Baseline up to Week 25 (after 24 weeks on treatment) Observed Value in Lactate Dehydrogenase (LDH) Baseline up to Week 25 (after 24 weeks on treatment) Observed Value in Hemoglobin Baseline up to Week 25 (after 24 weeks on treatment) Change from Baseline in Platelet Count Baseline up to Week 25 (after 24 weeks on treatment) Change from Baseline in Lactate Dehydrogenase (LDH) Baseline up to Week 25 (after 24 weeks on treatment) Change from Baseline in Hemoglobin Baseline up to Week 25 (after 24 weeks on treatment) Mean Change From Baseline in Fatigue (in Adult Participants only) Baseline up to Week 25 (after 24 weeks on treatment) 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 \[better score\].Percentage of Participants with Platelet Count >= Lower Limits of Normal (LLN) (Naive Cohort only) 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) Baseline up to Week 25 (after 24 weeks on treatment) Percentage of Participants with >=25% Decrease in Serum Creatinine (Naive Cohort only) Baseline up to Week 25 (after 24 weeks on treatment) Percentage of Participants with Maintained Thrombotic Microangiopathy Control (mTMAc) (Switch Cohort only) Baseline up to Week 25 (after 24 weeks on treatment) Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, Malignant Hypertension (Including Malignant Renal Hypertension) and Infections (Including Meningococcal Meningitis) Up to 8 years Number of Participants with AEs Leading to Study Drug Discontinuation 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 Up to Week 25 Serum Concentrations of Crovalimab Over Time Up to 8 years Prevalence of Anti-Crovalimab Antibodies at Baseline Baseline Percentage of Participants with Anti-Crovalimab Antibodies Up to 8 years Observed value of Pharmacodynamic Markers (CH50, Free/Total C5) Up to 8 years Time to cTMAr (Naive Cohort only) Up to 8 years Duration of cTMAr (Naive Cohort only) Up to 8 years Percentage of Participants with Ongoing cTMAr (Naive Cohort only) At Week 25 Percentage of Participants with Adverse Events (AEs) Up to 8 years
Trial Locations
- Locations (50)
University of California Irvine Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
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
🇺🇸Saint 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
Scroll for more (40 remaining)University of California Irvine Chao Family Comprehensive Cancer Center🇺🇸Orange, California, United States