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Atypical Hemolytic Uremic SyndromePhase 3COMMUTE-aNCT04861259

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

A Phase 3 study testing Crovalimab in people with Atypical Hemolytic Uremic Syndrome, run by Hoffmann-La Roche at 42 sites in 16 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

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

Who is it for?
Ages 12 years and older
Conditions the study is for
Atypical Hemolytic Uremic Syndrome
What is being tested?
Crovalimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
42 sitesin 16 countries
Study dates
22 Oct 2021to 20 Aug 2029
Phase
Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

42 sites in 16 countries.

42 sites in 16 countries

United States6 sites

  • Emory Children's Center

    Atlanta, Georgia, 20010

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43212

  • UT Health Science Center

    San Antonio, Texas, 78229

  • Univ of CA San Francisco

    San Francisco, California, 94143

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

Germany4 sites

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

    Cologne, 50937

  • Universitätsklinikum Essen

    Essen, 45122

  • Klinik für Nephrologie des Universitätsklinikum Essen

    Essen, 45147

  • Medizinische Hochschule Hannover

    Hanover, 30625

Other trials in Germany

Mexico4 sites

  • Hospital General de México

    Distrito Federal, Mexico CITY (federal District), 06726

  • Instituto Nacional de Ciencias

    Mexico City, Mexico CITY (federal District), 14080

  • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

    Monterrey, Nuevo León, 64460

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

    Zapopan, 45116

Other trials in Mexico

Turkey (Türkiye)4 sites

  • Istanbul University Istanbul Medical Faculty

    Istanbul, 34390

  • Kocaeli University Medical Faculty

    Kocaeli, 41380

  • Necmettin Erbakan University Meram Medical Faculty

    Konya, 42080

  • Malatya Park Hospital

    Malatya, 44330

Other trials in Turkey (Türkiye)

Brazil3 sites

  • Santa Casa de Misericordia

    Belo Horizonte, Minas Gerais, 30150-221

  • UPECLIN Hospital das Clinicas da Faculdade de Medicina de Botucatu

    Botucatu, São Paulo, 18618-686

  • Hospital das Clinicas - FMUSP

    São Paulo, São Paulo, 05403-000

Other trials in Brazil

France3 sites

  • Hopital Lapeyronie

    Montpellier, 34295

  • Hôpital Robert Debré

    Paris, 75019

  • Hopital Tenon

    Paris, 75970

Other trials in France

Israel3 sites

  • Rambam Medical Center

    Haifa, 3109601

  • Rabin Medical Center

    Petah Tikva, 49100

  • Sheba MC

    Ramat Gan, 52621

Other trials in Israel

Japan3 sites

  • Nagoya University Hospital

    Aichi, 466-8560

  • Saitama Medical University Hospital

    Saitama, 350-0451

  • The University of Tokyo Hospital

    Tokyo, 113-8655

Other trials in Japan

Spain3 sites

  • Complejo Hospitalario Universitario A Coruña (CHUAC)

    A Coruña, 15006

  • Hospital Clinic i Provincial

    Barcelona, 08036

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

Other trials in Spain

India2 sites

  • Medanta-The Medicity

    Gurgaon, Haryana, 122001

  • All India Institute Of Medical Sciences (AIIMS)

    New Delhi, National Capital Territory of Delhi, 110029

Other trials in India

Italy2 sites

  • A.O. Universitaria S. Martino Di Genova

    Genoa, Liguria, 16132

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Rome, Lazio, 00168

Other trials in Italy

Belgium1 site

  • UZ Leuven Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Canada1 site

  • Vancouver General Hospital

    Vancouver, British Columbia, V5Z 2S3

Other trials in Canada

China1 site

  • Peking University First Hospital

    Beijing, 100034

Other trials in China

Hungary1 site

  • Del- Pesti Centrumkorhaz- Szent Laszlo Korhaz Telephely

    Budapest, 1097

Other trials in Hungary

Poland1 site

  • Instytut ?Centrum Zdrowia Matki Polki

    Lodz, 93-338

Other trials in Poland

About this study

Official title: A Phase III, Multicenter, Single-Arm Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Adult and Adolescent Patients With Atypical Hemolytic Uremic Syndrome (aHUS)

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

Being tested
Crovalimab
Medical subject headings
Atypical Hemolytic Uremic Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CrovalimabDrug

    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).

Study groups in NCT04861259
Study groupRoleWhat they receive
CrovalimabExperimentalParticipants 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.
Receives: Drug: Crovalimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants with Complete Thormbotic Microangiopathy Response (cTMAr)

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

Secondary outcomes (25)

  1. Change from Baseline in Dialysis Status

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

  2. Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)

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

  3. Percentage of Participants with Change from Baseline in Chronic Kidney Disease (CKD) Stage

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

  4. Observed Value in Platelet Count

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

  5. Observed Value in Lactate Dehydrogenase (LDH)

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

  6. Observed Value in Hemoglobin

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

  7. Change from Baseline in Platelet Count

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

  8. Change from Baseline in Lactate Dehydrogenase (LDH)

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

  9. Change from Baseline in Hemoglobin

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

  10. 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].

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

  11. Percentage of Participants with Platelet Count >= Lower Limits of Normal (LLN) (Naive Cohort only)

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

  12. Percentage of Participants with Normalization of LDH (i.e. =< Upper Limit of Normal (ULN)) (Naive Cohort only)

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

  13. Percentage of Participants with >=25% Decrease in Serum Creatinine (Naive Cohort only)

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

  14. Time to cTMAr (Naive Cohort only)

    Measured: Up to 8 years

  15. Duration of cTMAr (Naive Cohort only)

    Measured: Up to 8 years

  16. Percentage of Participants with Ongoing cTMAr (Naive Cohort only)

    Measured: At Week 25

  17. Percentage of Participants with Maintained Thrombotic Microangiopathy Control (mTMAc) (Switch Cohort only)

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

  18. Percentage of Participants with Adverse Events (AEs)

    Measured: Up to 8 years

  19. Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, Malignant Hypertension (Including Malignant Renal Hypertension) and Infections (Including Meningococcal Meningitis)

    Measured: Up to 8 years

  20. Number of Participants with AEs Leading to Study Drug Discontinuation

    Measured: Up to 8 years

  21. 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

    Measured: Up to Week 25

  22. Serum Concentrations of Crovalimab Over Time

    Measured: Up to 8 years

  23. Prevalence of Anti-Crovalimab Antibodies at Baseline

    Measured: Baseline

  24. Percentage of Participants with Anti-Crovalimab Antibodies

    Measured: Up to 8 years

  25. Observed value of Pharmacodynamic Markers (CH50, Free/Total C5)

    Measured: Up to 8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2021
  2. Study start22 Oct 2021
  3. Primary completion9 Oct 2025
  4. Study completion20 Aug 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04861259
Sponsor's protocol ID
BO42353
Other IDs
2020-002475-35, 2023-505089-27-00, 2023
Acronym
COMMUTE-a
Status last verified
Jul 2026
First submitted
23 Apr 2021
Last updated
21 Jul 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing

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