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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04861259
Other study ID # BO42353
Secondary ID 2020-002475-35
Status Recruiting
Phase Phase 3
First received
Last updated
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
Health authority
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.

Study Design


Related Conditions & MeSH terms


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
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