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

Atypical Hemolytic Uremic Syndrome Clinical Trial

— COMMUTE-p  

Official title:

A Phase III, Multicenter, Single-Arm Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Pediatric Patients With Atypical Hemolytic Uremic Syndrome (aHUS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04958265
• Other study ID #: BO42354
• Secondary ID: 2020-002437-15
• Status: Recruiting
• Phase: Phase 3
• 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
• 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.

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 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