A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS)

NCT04958265 | Active Not Recruiting Phase 3 FDA Drug

• 3 other identifiers: BO423542020-002437-152023-505638-82-00
• Study Type: interventional
• Target: 41
• Locations: 10 countries
• Sites: 20

Brief Summary

This study aims to evaluate the efficacy and safety of crovalimab in pediatric participants with aHUS.

Conditions

Atypical Hemolytic Uremic Syndrome

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with complete TMA response (cTMAr) (Naive Cohort only)

  Baseline up to Week 25 (after 24 weeks on treatment)

Secondary Outcomes (24)

• Change from Baseline in Dialysis Status

  Baseline up to Week 25 (after 24 weeks on treatment)

• Change in Estimated Glomerular Filtration Rate (eGFR) (Naive and Switch Cohorts)

  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)

  Baseline up to Week 25 (after 24 weeks on treatment)

• Observed Value in Platelet Count (Naive and Switch Cohorts)

  Baseline up to Week 25 (after 24 weeks on treatment)

• Observed Value in Lactate Dehydrogenase (LDH) (mg/dL) (Naive and Switch Cohorts)

  Baseline up to Week 25 (after 24 weeks on treatment)

Study Arms (1)

Crovalimab

EXPERIMENTAL

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 C5 inhibitor and \[3\] Pretreated Cohort (includes C5 SNP (Single Nucleotide Polymorphism) participants) - participants who received treatment with another C5 inhibitor and subsequently discontinued it.

Drug: Crovalimab

Interventions

Crovalimab DRUG

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.

Crovalimab

Eligibility Criteria

• Age: 28 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Body weight \>= 5 kg at screening.
• Vaccination against Neisseria meningitis serotypes A, C, W, and Y; vaccination against serotype B, according to national vaccination recommendations.
• Vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae, according to national vaccination recommendations.
• For patients 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.
• 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).
• Poorly controlled TMA following treatment with another C5 inhibitor (for C5 SNP participants in the Pretreated Cohort only).
• Known C5 polymorphism (for C5 SNP participants in the Pretreated Cohort only).

You may not qualify if:

• 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 HIV test.
• Active systemic bacterial, viral, or fungal infection within 14 days before first crovalimab administration.
• Presence of fever (\>= 38°C) before the first crovalimab administration (If fevers are solely due to the underlying aHUS pathology, and there is no evidence or suspicion of a systemic infection, participants may enroll).
• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Chugai Pharmaceutical: collaborator

Study Sites (20)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Nebraska

Omaha, Nebraska, 68198, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Inst. Da Criança- Faculdade de Medicina Usp

São Paulo, São Paulo, 05403-900, Brazil

Location

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Peking University First Hospital

Beijing, 100034, China

Location

Beijing Children's Hospital, Capital Medical University

Beijing, 100045, China

Location

The children's hospital , Zhejiang university school of medicine

Hangzhou, 310051, China

Location

Hôpital Arnaud de Villeneuve

Montpellier, 34295, France

Location

Gh Necker Enfants Malades

Paris, 75743, France

Location

Institute of Kidney Diseases and Research Centre

Ahmedabad, Gujarat, 380016, India

Location

Medanta-The Medicity

Gurgaon, Haryana, 122001, India

Location

All India Institute Of Medical Sciences (AIIMS)

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Aichi Children?s Health and Medical Center

Aichi, 474-8710, Japan

Location

Chiba Children's Hospital

Chibashi, Chibaken, 266-0007, Japan

Location

Hospital de Especialidades Puerta de Hierro S.A de C.V.

Zapopan, 45116, Mexico

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-294, Poland

Location

Instytut ?Centrum Zdrowia Matki Polki

Lodz, 93-338, Poland

Location

MeSH Terms

Conditions

Atypical Hemolytic Uremic Syndrome

Condition Hierarchy (Ancestors)

Hemolytic-Uremic Syndrome; Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2021
• First Posted: July 12, 2021
• Study Start: November 17, 2021
• Primary Completion: July 4, 2025
• Study Completion (Estimated): May 19, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

BR (1); FR (2); BE (2); CA (1); US (3); IN (3); PL (2); CN (3); JP (2); ME (1)