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

NCT04861259 | Active Not Recruiting Phase 3 FDA Drug

• 3 other identifiers: BO423532020-002475-352023-505089-27-00
• Study Type: interventional
• Target: 83
• Locations: 16 countries
• Sites: 42

Brief Summary

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

Conditions

Atypical Hemolytic Uremic Syndrome

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with Complete Thormbotic Microangiopathy Response (cTMAr)

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

Secondary Outcomes (25)

• 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)

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 Complement Component 5 (C5) inhibitor and \[3\] C5 Single Nucleotide Polymorphism (C5 inhibitor) Cohort - participants with documented C5 polymorphism.

Drug: Crovalimab

Interventions

Crovalimab DRUG

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).

Crovalimab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

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 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.

Sponsors & Collaborators

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

Study Sites (42)

Univ of CA San Francisco

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Emory Children's Center

Atlanta, Georgia, 20010, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43212, United States

Location

UT Health Science Center

San Antonio, Texas, 78229, United States

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Santa Casa de Misericordia

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

UPECLIN Hospital das Clinicas da Faculdade de Medicina de Botucatu

Botucatu, São Paulo, 18618-686, Brazil

Location

Hospital das Clinicas - FMUSP

São Paulo, São Paulo, 05403-000, Brazil

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 2S3, Canada

Location

Peking University First Hospital

Beijing, 100034, China

Location

Hopital Lapeyronie

Montpellier, 34295, France

Location

Hôpital Robert Debré

Paris, 75019, France

Location

Hopital Tenon

Paris, 75970, France

Location

Klinik II für Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin

Cologne, 50937, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

Klinik für Nephrologie des Universitätsklinikum Essen

Essen, 45147, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Del- Pesti Centrumkorhaz- Szent Laszlo Korhaz Telephely

Budapest, 1097, Hungary

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

Rambam Medical Center

Haifa, 3109601, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Sheba MC

Ramat Gan, 52621, Israel

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, 00168, Italy

Location

A.O. Universitaria S. Martino Di Genova

Genoa, Liguria, 16132, Italy

Location

Nagoya University Hospital

Aichi, 466-8560, Japan

Location

Saitama Medical University Hospital

Saitama, 350-0451, Japan

Location

The University of Tokyo Hospital

Tokyo, 113-8655, Japan

Location

Hospital General de México

Distrito Federal, Mexico CITY (federal District), 06726, Mexico

Location

Instituto Nacional de Ciencias

Mexico City, Mexico CITY (federal District), 14080, Mexico

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, Nuevo León, 64460, Mexico

Location

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

Zapopan, 45116, Mexico

Location

Instytut ?Centrum Zdrowia Matki Polki

Lodz, 93-338, Poland

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, 15006, Spain

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Istanbul University Istanbul Medical Faculty

Istanbul, 34390, Turkey (Türkiye)

Location

Kocaeli University Medical Faculty

Kocaeli, 41380, Turkey (Türkiye)

Location

Necmettin Erbakan University Meram Medical Faculty

Konya, 42080, Turkey (Türkiye)

Location

Malatya Park Hospital

Malatya, 44330, Turkey (Türkiye)

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: April 23, 2021
• First Posted: April 27, 2021
• Study Start: October 22, 2021
• Primary Completion: October 9, 2025
• Study Completion (Estimated): August 20, 2029
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

IT (2); BR (3); CA (1); BE (1); HU (1); ES (3); PL (1); CN (1); TU (4); FR (3); IL (3); ME (4); JP (3); US (6); DE (4); IN (2)