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

Atypical Hemolytic Uremic Syndrome Clinical Trial

— COMMUTE-a  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04861259
• Other study ID #: BO42353
• Secondary ID: 2020-002475-35
• Status: Recruiting
• Phase: Phase 3
• Start date: October 22, 2021
• Est. completion date: December 7, 2029

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BO42353 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 7, 2029
• Est. primary completion date: June 13, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atypical Hemolytic Uremic Syndrome
• Azotemia
• Hemolysis
• Hemolytic-Uremic Syndrome
• Syndrome

Intervention

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).

Locations

Country	Name	City	State
Belgium	UZ Leuven Gasthuisberg	Leuven
Brazil	Santa Casa de Misericordia; de Belo Horizonte	Belo Horizonte	MG
Brazil	UPECLIN Hospital das Clinicas da Faculdade de Medicina de Botucatu	Botucatu	SP
Brazil	Hospital das Clinicas - FMUSP	Sao Paulo	SP
Brazil	Hospital Samaritano	São Paulo	SP
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
China	Peking University First Hospital; NEPHROLOGY	Beijing
China	Beijing Children's Hospital, Capital Medical University	Beijing City
France	Hôpital Arnaud de Villeneuve; Néphrologie pédiatrique	Montpellier
France	Hopital Lapeyronie; Nephrologie	Montpellier
France	Gh Necker Enfants Malades; Nephrologie	Paris
France	Hôpital Robert Debré; Nephrologie pediatrique	Paris
France	Hopital Tenon; Service SINRA	Paris
Germany	Klinik für Nephrologie des Universitätsklinikum Essen; Klinik für Infektiologie - MFZ	Essen
Germany	Universitätsklinikum Essen; Klinik für Kinder- und Jugendmedizin Pädiatrie II	Essen
Germany	Medizinische Hochschule Hannover; Klinik für Nieren- und Hochdruckerkrankungen	Hannover
Germany	Klinik II für Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin	Köln
Hungary	Del- Pesti Centrumkorhaz- Szent Laszlo Korhaz Telephely	Budapest
India	Medanta-The Medicity	Gurgaon	Haryana
India	Sawai Man Singh Hospital and Medical College	Jaipur	Rajasthan
India	All India Institute Of Medical Sciences (AIIMS)	New Delhi	Delhi
Israel	Rambam Medical Center; Department of Nephrology and Hypertension	Haifa
Israel	Rabin Medical Center; Nephrology	Petach Tikva
Israel	Sheba MC; Nephrology	Ramat-Gan
Italy	Az. Osp. Careggi; Reparto Di Nefrologia, Dialisi E Trapianti	Firenze	Toscana
Italy	A.O. Universitaria S. Martino Di Genova; Nefrologia	Genova	Liguria
Italy	Presidio Ospedaliero Maggiore Policlinico Fondazione IRCCS; Pad Croff Div Nefrologia Dialisi	Milano	Lombardia
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS; U.O.C. Nefrologia	Roma	Lazio
Japan	Nagoya University Hospital	Aichi
Japan	Mie University Hospital	Mie
Japan	Saitama Medical University Hospital	Saitama
Japan	The University of Tokyo Hospital	Tokyo
Mexico	Instituto Nacional de Ciencias; Medicas y Nutricion; Salvador Zubiran	Ciudad de México	Mexico CITY (federal District)
Mexico	Centro para el Desarrollo de la Medicina y de Asistencia	Culiacán Rosales	Sinaloa
Mexico	Hospital General de México	Distrito Federal	Mexico CITY (federal District)
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEON
Mexico	Hospital de Especialidades Puerta de Hierro S.A de C.V.	Zapopan	Jalisco
New Zealand	Auckland City Hospital; Renal Unit, Level 15	Auckland
New Zealand	New Zealand Clinical Research - Christchurch	Christchurch
New Zealand	Dunedin Hospital; Otago District Health Board	Dunedin
Peru	Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion	Bellavista
Peru	Hospital Nacional Dos de Mayo	Lima
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadci?nienia Dzieci i Mlodziezy	Gdansk
Poland	Instytut ?Centrum Zdrowia Matki Polki; Klinika Pediatrii i Immunologii i Nefrologii	Lodz
Poland	SAMODZIELNY PUBLICZNY CENTRALNY SZPITAL KLINICZNY; Department KLINIKA NEFROLOGII, DIALIZOTERAPII I C	Warszawa
Poland	Szpital Kliniczny nr 1 im. prof. Szyszko; Oddz. Nefrologii Dzieciecej z Pododdzia?em Dializoterapii	Zabrze
South Africa	Red Cross War Memorial Children's Hospital; Pediatric Nephrology	Rondebosch
South Africa	Inkosi Albert Luthuli Central Hospital; Pediatric Nephrology	Umkumbaan
Spain	Hospital Clinic i Provincial; Servicio de Nefrologia	Barcelona
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Nefrologia	La Coruna	LA Coruña
Spain	Hospital Universitario 12 de Octubre; Servicio de Nefrologia	Madrid
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Turkey	Istanbul University Istanbul Medical Faculty; Department of Internal Medicine	Istanbul
Turkey	Erciyes University Medical Faculty; Internal Medicine	Kayseri
Turkey	Kocaeli University Medical Faculty	Kocaeli
Turkey	Necmettin Erbakan University Meram Medical Faculty ; Internal Diseases	Konya
Turkey	Inonu University Faculty of Medicine Turgut Ozal Medical Center	Malatya
Turkey	Malatya Park Hospital	Malatya
Turkey	Ondokuz Mayis Univ. Med. Fac.	Samsun
United States	Emory Children's Center	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Brigham and Womens Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Memorial Healthcare Systems	Hollywood	Florida
United States	University of California Irvine Chao Family Comprehensive Cancer Center	Orange	California
United States	University of California Davis	Sacramento	California
United States	Washington University	Saint Louis	Missouri
United States	UT Health Science Center; SouthTexas Pediatric Blood and Cancer Ctr	San Antonio	Texas
United States	Univ of CA San Francisco	San Francisco	California
United States	SUNY at Stony Brook	Stony Brook	New York

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Chugai Pharmaceutical

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  China,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Japan,  Mexico,  New Zealand,  Peru,  Poland,  South Africa,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with complete TMA response (cTMAr)		Baseline up to Week 25
Secondary	Change from Baseline in Dialysis Status		Baseline up to Week 25
Secondary	Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)		Baseline up to Week 25
Secondary	Percentage of Participants with Change from Baseline in Chronic Kidney Disease (CKD) stage		Baseline up to Week 25
Secondary	Observed Value in Platelet Count		Baseline up to Week 25
Secondary	Observed Value in Lactate Dehydrogenase (LDH)		Baseline up to Week 25
Secondary	Observed Value in Hemoglobin		Baseline up to Week 25
Secondary	Change from Baseline in Platelet Count		Baseline up to Week 25
Secondary	Change from Baseline in Lactate Dehydrogenase (LDH)		Baseline up to Week 25
Secondary	Change from Baseline in Hemoglobin		Baseline up to Week 25
Secondary	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
Secondary	Percentage of Participants with Platelet Count >= Lower Limits of Normal (LLN) (Naive Cohort only)		Baseline up to Week 25
Secondary	Percentage of Participants with Normalization of LDH (i.e. =< Upper Limit of Normal (ULN)) (Naive Cohort only)		Baseline up to Week 25
Secondary	Percentage of Participants with >=25% decrease in Serum Creatinine (Naive Cohort only)		Baseline up to Week 25
Secondary	Time to complete TMA response (cTMAr) (Naive Cohort only)		Up to 9 years
Secondary	Duration of complete TMA response (cTMAr) (Naive Cohort only)		Up to 9 years
Secondary	Percentage of Participants with complete TMA response (cTMAr) (Naive Cohort only)		Week 25
Secondary	Percentage of Participants with maintained TMA control (mTMAc) (Switch Cohort only)		Baseline through Week 25
Secondary	Percentage of Participants with Adverse Events (AEs)		Up to 9 years
Secondary	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
Secondary	Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation		Up to 9 years
Secondary	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
Secondary	Serum Concentrations of Crovalimab Over Time		Up to 9 years
Secondary	Percentage of Participants with Anti-Crovalimab Antibodies		Up to 9 years