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

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.

Study Overview

• Status: Recruiting
• Conditions: Atypical Hemolytic Uremic Syndrome
• Intervention / Treatment: Drug: Crovalimab

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BO42353 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven Gasthuisberg
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30150-221
      • Active, not recruiting
      • Santa Casa de Misericordia; de Belo Horizonte
  • SP
    • Botucatu, SP, Brazil, 18618-686
      • Active, not recruiting
      • UPECLIN Hospital das Clinicas da Faculdade de Medicina de Botucatu
    • Sao Paulo, SP, Brazil, 05403-010
      • Active, not recruiting
      • Hospital das Clinicas - FMUSP
    • São Paulo, SP, Brazil, 01232-010
      • Withdrawn
      • Hospital Samaritano
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1L8
      • Recruiting
      • Vancouver General Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Recruiting
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Toronto General Hospital
• China
  • Beijing, China, 100034
    • Recruiting
    • Peking University First Hospital; NEPHROLOGY
  • Beijing City, China, 100045
    • Recruiting
    • Beijing Children's Hospital, Capital Medical University
• France
  • Montpellier, France, 34295
    • Recruiting
    • Hopital Lapeyronie; Nephrologie
  • Montpellier, France, 34295
    • Recruiting
    • Hôpital Arnaud de Villeneuve; Néphrologie pédiatrique
  • Paris, France, 75019
    • Recruiting
    • Hôpital Robert Debré; Nephrologie pediatrique
  • Paris, France, 75743
    • Recruiting
    • Gh Necker Enfants Malades; Nephrologie
  • Paris, France, 75970
    • Recruiting
    • Hopital Tenon; Service SINRA
• Germany
  • Essen, Germany, 45122
    • Recruiting
    • Universitätsklinikum Essen; Klinik für Kinder- und Jugendmedizin Pädiatrie II
  • Essen, Germany, 45147
    • Recruiting
    • Klinik für Nephrologie des Universitätsklinikum Essen; Klinik für Infektiologie - MFZ
  • Hannover, Germany, 30625
    • Recruiting
    • Medizinische Hochschule Hannover; Klinik für Nieren- und Hochdruckerkrankungen
  • Köln, Germany, 50937
    • Recruiting
    • Klinik II für Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin
• Hungary
  • Budapest, Hungary, 1097
    • Recruiting
    • Del- Pesti Centrumkorhaz- Szent Laszlo Korhaz Telephely
• India
  • Delhi
    • New Delhi, Delhi, India, 110029
      • Recruiting
      • All India Institute of Medical Sciences (AIIMS)
  • Haryana
    • Gurgaon, Haryana, India, 122001
      • Recruiting
      • Medanta-The Medicity
  • Rajasthan
    • Jaipur, Rajasthan, India, 302004
      • Recruiting
      • Sawai Man Singh Hospital and Medical College
• Israel
  • Haifa, Israel, 3109601
    • Active, not recruiting
    • Rambam Medical Center; Department of Nephrology and Hypertension
  • Petach Tikva, Israel, 0049100
    • Recruiting
    • Rabin Medical Center; Nephrology
  • Ramat-Gan, Israel, 5262000
    • Recruiting
    • Sheba MC; Nephrology
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS; U.O.C. Nefrologia
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Recruiting
      • A.O. Universitaria S. Martino Di Genova; Nefrologia
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Recruiting
      • Presidio Ospedaliero Maggiore Policlinico Fondazione IRCCS; Pad Croff Div Nefrologia Dialisi
  • Toscana
    • Firenze, Toscana, Italy, 50139
      • Recruiting
      • Az. Osp. Careggi; Reparto Di Nefrologia, Dialisi E Trapianti
• Japan
  • Aichi, Japan, 466-8560
    • Recruiting
    • Nagoya University Hospital
  • Mie, Japan, 514-8507
    • Recruiting
    • Mie University Hospital
  • Saitama, Japan, 350-0451
    • Active, not recruiting
    • Saitama Medical University Hospital
  • Tokyo, Japan, 113-8655
    • Recruiting
    • The University of Tokyo Hospital
• Mexico
  • Jalisco
    • Zapopan, Jalisco, Mexico, 45116
      • Recruiting
      • Hospital de Especialidades Puerta de Hierro S.A de C.V.
  • Mexico CITY (federal District)
    • Ciudad de México, Mexico CITY (federal District), Mexico, 14080
      • Recruiting
      • Instituto Nacional de Ciencias; Medicas y Nutricion; Salvador Zubiran
    • Distrito Federal, Mexico CITY (federal District), Mexico, 06726
      • Active, not recruiting
      • Hospital General de Mexico
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64460
      • Recruiting
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
  • Sinaloa
    • Culiacán Rosales, Sinaloa, Mexico, 80230
      • Withdrawn
      • Centro para el Desarrollo de la Medicina y de Asistencia
• New Zealand
  • Auckland, New Zealand, 1001
    • Recruiting
    • Auckland City Hospital; Renal Unit, Level 15
  • Christchurch, New Zealand, 8011
    • Recruiting
    • New Zealand Clinical Research - Christchurch
  • Dunedin, New Zealand, 9054
    • Recruiting
    • Dunedin Hospital; Otago District Health Board
• Peru
  • Bellavista, Peru, Callao 2
    • Recruiting
    • Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion
  • Lima, Peru
    • Recruiting
    • Hospital Nacional Dos de Mayo
• Poland
  • Gdansk, Poland, 80-952
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadci?nienia Dzieci i Mlodziezy
  • Lodz, Poland, 93-338
    • Active, not recruiting
    • Instytut ?Centrum Zdrowia Matki Polki; Klinika Pediatrii i Immunologii i Nefrologii
  • Warszawa, Poland, 02-097
    • Recruiting
    • SAMODZIELNY PUBLICZNY CENTRALNY SZPITAL KLINICZNY; Department KLINIKA NEFROLOGII, DIALIZOTERAPII I C
  • Zabrze, Poland, 41-800
    • Recruiting
    • Szpital Kliniczny nr 1 im. prof. Szyszko; Oddz. Nefrologii Dzieciecej z Pododdzia?em Dializoterapii
• South Africa
  • Rondebosch, South Africa, 7700
    • Recruiting
    • Red Cross War Memorial Children's Hospital; Pediatric Nephrology
  • Umkumbaan, South Africa, 4091
    • Withdrawn
    • Inkosi Albert Luthuli Central Hospital; Pediatric Nephrology
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic i Provincial; Servicio de Nefrologia
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre; Servicio de Nefrologia
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocío
  • LA Coruña
    • La Coruna, LA Coruña, Spain, 15006
      • Recruiting
      • Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Nefrologia
• Turkey
  • Istanbul, Turkey, 34390
    • Recruiting
    • Istanbul University Istanbul Medical Faculty; Department of Internal Medicine
  • Kayseri, Turkey, 38039
    • Withdrawn
    • Erciyes University Medical Faculty; Internal Medicine
  • Kocaeli, Turkey, 41380
    • Active, not recruiting
    • Kocaeli University Medical Faculty
  • Konya, Turkey, 42080
    • Recruiting
    • Necmettin Erbakan University Meram Medical Faculty ; Internal Diseases
  • Malatya, Turkey, 44280
    • Withdrawn
    • Inonu University Faculty of Medicine Turgut Ozal Medical Center
  • Malatya, Turkey, 44330
    • Recruiting
    • Malatya Park Hospital
  • Samsun, Turkey, 55139
    • Withdrawn
    • Ondokuz Mayis Univ. Med. Fac.
• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • University of California Irvine Chao Family Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California Davis
    • San Francisco, California, United States, 94143-0435
      • Recruiting
      • Univ of CA San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
  • Florida
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • Memorial Healthcare Systems
  • Georgia
    • Atlanta, Georgia, United States, 20010
      • Recruiting
      • Emory Children's Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Womens Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Recruiting
      • Washington University
  • New York
    • Stony Brook, New York, United States, 11790
      • Recruiting
      • SUNY At Stony Brook
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43212
      • Recruiting
      • The Ohio State University Wexner Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Active, not recruiting
      • UT Health Science Center; SouthTexas Pediatric Blood and Cancer Ctr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 ) within 7 days before the first crovalimab administration
• 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).
• Documented 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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 C5 inhibitor and [3] C5 SNP (Single Nucleotide Polymorphism) Cohort - participants with documented C5 polymorphism.

Drug: Crovalimab; Crovalimab will be administered at a dose of 1000 mg IV (for participants with body weight between 40 and 100kg) 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 SC. On Week 5 and Q4W thereafter, it will be administered at a dose of 680 mg SC (for participants with body weight between 40 and 100kg) or 1020 mg SC (for participants with body weight >=100kg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with complete TMA response (cTMAr)	Baseline up to Week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Platelet Count >= Lower Limits of Normal (LLN) (Naive Cohort only)		Baseline up to Week 25
Percentage of Participants with Normalization of LDH (i.e. =< Upper Limit of Normal (ULN)) (Naive Cohort only)		Baseline up to Week 25
Percentage of Participants with >=25% decrease in Serum Creatinine (Naive Cohort only)		Baseline up to Week 25
Percentage of Participants with complete TMA response (cTMAr) (Naive Cohort only)		Week 25
Percentage of Participants with maintained TMA control (mTMAc) (Switch Cohort only)		Baseline through Week 25
Change from Baseline in Dialysis Status		Baseline up to Week 25
Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)		Baseline up to Week 25
Percentage of Participants with Change from Baseline in Chronic Kidney Disease (CKD) stage		Baseline up to Week 25
Observed Value in Platelet Count		Baseline up to Week 25
Observed Value in Lactate Dehydrogenase (LDH)		Baseline up to Week 25
Observed Value in Hemoglobin		Baseline up to Week 25
Change from Baseline in Platelet Count		Baseline up to Week 25
Change from Baseline in Lactate Dehydrogenase (LDH)		Baseline up to Week 25
Change from Baseline in Hemoglobin		Baseline up to Week 25
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].	Baseline up to Week 25
Time to complete TMA response (cTMAr) (Naive Cohort only)		Up to 9 years
Duration of complete TMA response (cTMAr) (Naive Cohort only)		Up to 9 years
Percentage of Participants with Adverse Events (AEs)		Up to 9 years
Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, Malignant Hypertension (including malignant renal hypertension) and Infections (including meningococcal meningitis)		Up to 9 years
Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation		Up to 9 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 9 years
Percentage of Participants with Anti-Crovalimab Antibodies		Up to 9 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Chugai Pharmaceutical
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2021
• Primary Completion (Estimated): June 13, 2025
• Study Completion (Estimated): December 7, 2029

Study Registration Dates

• First Submitted: April 23, 2021
• First Submitted That Met QC Criteria: April 23, 2021
• First Posted (Actual): April 27, 2021

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Hematologic Diseases; Anemia; Thrombocytopenia; Blood Platelet Disorders; Anemia, Hemolytic; Thrombotic Microangiopathies; Uremia; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cytopenia; Syndrome; Azotemia; Hemolysis; Hemolytic-Uremic Syndrome; Atypical Hemolytic Uremic Syndrome
• Other Study ID Numbers: BO42353; 2020-002475-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No