Atypical Hemolytic Uremic Syndrome Clinical Trial
— COMMUTE-aOfficial 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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Hoffmann-La Roche | Chugai Pharmaceutical |
United States, Belgium, Brazil, Canada, China, France, Germany, Hungary, India, Israel, Italy, Japan, Mexico, New Zealand, Peru, Poland, South Africa, Spain, Turkey,
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 |
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