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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04958265
Other study ID # BO42354
Secondary ID 2020-002437-15
Status Recruiting
Phase Phase 3
First received
Last updated
Start date November 17, 2021
Est. completion date September 16, 2029

Study information

Verified date June 2024
Source Hoffmann-La Roche
Contact Reference Study ID Number: BO42354 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 pediatric participants with aHUS.


Recruitment information / eligibility

Status Recruiting
Enrollment 45
Est. completion date September 16, 2029
Est. primary completion date December 12, 2025
Accepts healthy volunteers No
Gender All
Age group 28 Days to 17 Years
Eligibility Inclusion Criteria: - Body weight >= 5 kg at screening. - Vaccination against Neisseria meningitis serotypes A, C, W, and Y; vaccination against serotype B, according to national vaccination recommendations. - Vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae, according to national vaccination recommendations. - For patients 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. - 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). - Poorly controlled TMA following treatment with another C5 inhibitor (for C5 SNP participants in the Pretreated Cohort only). - Known C5 polymorphism (for C5 SNP participants in the Pretreated 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 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 Cohort only). - Receiving PE/PI within 8 weeks of the first crovalimab administration (Switch Cohort only). - Positive for active Hepatitis B and/or C infections (HBV/HCV) (for Switch Cohort and switching C5 SNP Pretreated 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 Diacylglycerol kinase e (DGKE) nephropathy.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Crovalimab
Crovalimab will be administered at a dose of 1000 mg intravenously (IV) (for participants weighing 40 to <100 kg) or 1500 mg IV (for participants weighing >=100 kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, crovalimab will be administered at a dose of 340 mg subcutaneously (SC). On Week 5 and Q4W thereafter, it will be administered at a dose of 680 mg SC (for participants weighing 40 to <100 kg) or 1020 mg SC (for participants weighing >=100 kg). Enrollment of participants weighing <40 kg will be staggered using two weight-based dose confirmation groups (Group 1 participants weighing >=20 kg to <40 kg, followed by Group 2 participants weighing >=5 kg to <20 kg). All participants will receive an initial IV loading dose, which will be followed by SC dosing at either Q2W or Q4W intervals (depending on body weight), until study completion.

Locations

Country Name City State
Belgium UZ Gent Gent
Belgium UZ Leuven Gasthuisberg Leuven
Belgium CHC MontLégia Liege
Brazil Santa Casa de Belo Horizonte; Centro de Hemodiálise Belo Horizonte MG
Brazil UPECLIN Hospital das Clinicas da Faculdade de Medicina de Botucatu Botucatu SP
Brazil Inst. Da Criança- Faculdade de Medicina Usp; Unidade de Pneumologia Sao Paulo SP
Canada CHU Sainte-Justine Montreal Quebec
China Beijing Children's Hospital, Capital Medical University Beijing City
China Peking University First Hospital Beijing City
China The children's hospital , Zhejiang university school of medicine Hangzhou City
China Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech Wuhan
France Hôpital Arnaud de Villeneuve; Néphrologie pédiatrique Montpellier
France Gh Necker Enfants Malades; Nephrologie Paris
France Hôpital Robert Debré; Nephrologie pediatrique Paris
France CHU de Toulouse - Hôpital des Enfants; Nephro - Rhumato - Medecine Interne - Hypertension Toulouse
Hungary Szegedi Tudományagyetem; Gyermekgyógyászati Klinika Szeged
India Medanta-The Medicity Gurgaon Haryana
India All India Institute Of Medical Sciences (AIIMS) New Delhi Delhi
Israel Rambam medical Center; Pediatric Nephrology Haifa
Italy Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Nefrologia Pediatrica Milano Lombardia
Japan Aichi Children?s Health and Medical Center Aichi
Japan Chiba Children's Hospital Chibashi, Chibaken
Japan Hiroshima Prefectural Hospital Hiroshima
Japan Yokohama City University Medical Center Kanagawa
Japan Okinawa Prefectural Nanbu Medical Center & Children's Medical Center Okinawa
Mexico Hospital de Especialidades Puerta de Hierro S.A de C.V. Zapopan Jalisco
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 Instytut Pomnik-Centrum Zdrowia Dziecka, Klinika Nefrologii, Transp. Nerek i Nadcisnienia Tetniczego 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
Spain Hospital Universitario Virgen del Rocío Sevilla
United States Children's Hospital Colorado Aurora Colorado
United States Cincinnati Children's Hospital Medical Center; Investigational Drug Services Cincinnati Ohio
United States Hackensack University Medical Center Hackensack New Jersey
United States Memorial Healthcare Systems Hollywood Florida
United States University of Nebraska; Pediatric Nephrology Omaha Nebraska
United States University of California Davis Medical Center; Gi and Hepatology Sacramento California
United States University Of Utah Hosp & Clin; Investigational Pharmacy Salt Lake City Utah
United States UT Health Science Center; SouthTexas Pediatric Blood and Cancer Ctr San Antonio Texas

Sponsors (2)

Lead Sponsor Collaborator
Hoffmann-La Roche Chugai Pharmaceutical

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  China,  France,  Hungary,  India,  Israel,  Italy,  Japan,  Mexico,  Poland,  South Africa,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants with complete TMA response (cTMAr) (Naive Cohort only) Baseline up to Week 25
Secondary Change from Baseline in Dialysis Status Baseline up to Week 25
Secondary Change in Estimated Glomerular Filtration Rate (eGFR) (Naive and Switch Cohorts) Baseline up to Week 25
Secondary Percentage of Participants with Change from Baseline in Chronic Kidney Disease (CKD) stage (Naive and Switch Cohorts) Baseline up to Week 25
Secondary Observed Value in Platelet Count (Naive and Switch Cohorts) Baseline up to Week 25
Secondary Observed Value in Lactate Dehydrogenase (LDH) (mg/dL) (Naive and Switch Cohorts) Baseline up to Week 25
Secondary Observed Value in Hemoglobin (mg/dL) (Naive and Switch Cohorts) Baseline up to Week 25
Secondary Change from Baseline in Platelet Count (Naive and Switch Cohorts) Baseline up to Week 25
Secondary Change from Baseline in Lactate Dehydrogenase (LDH) (mg/dL) (Naive and Switch Cohorts) Baseline up to Week 25
Secondary Change from Baseline in Hemoglobin (mg/dL) (Naive and Switch Cohorts) Baseline up to Week 25
Secondary Percentage of Participants with Platelet Count >= LLN (Naive Cohort only) Baseline up to Week 25
Secondary Percentage of Participants with Normalisation of LDH (i.e., =< Upper Limit 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 8 years
Secondary Duration of complete TMA response (cTMAr) (Naive Cohort only) Up to 8 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 8 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 8 years
Secondary Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation Up to 8 years
Secondary Percentage of Participants with Clinical Manifestations of Drug-Target-Drug Complex (DTDC) formation amongst participants who switched to crovalimab treatment from eculizumab/ravulizumab treatment (Switch Cohort and switching Pretreated participants) Up to Week 25
Secondary Serum Concentrations of Crovalimab over time Up to 8 years
Secondary Percentage of Participants with Anti-Crovalimab Antibodies Up to 8 years
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