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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04958265

Collaborator

Chugai Pharmaceutical (Industry)

Enrollment

Locations

Arm

Anticipated Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Atypical Hemolytic Uremic Syndrome	Drug: Crovalimab	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Nov 17, 2021

Anticipated Primary Completion Date :

Dec 12, 2025

Anticipated Study Completion Date :

Sep 16, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Crovalimab Participants will be enrolled in three cohorts: [1] Naive Cohort - participants who have not been previously treated with complement inhibitor therapy; [2] Switch Cohort - participants who switch to crovalimab from another C5 inhibitor and [3] Pretreated Cohort (includes C5 SNP (Single Nucleotide Polymorphism) participants) - participants who received treatment with another C5 inhibitor and subsequently discontinued it.	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.

Arm

Intervention/Treatment

Experimental: Crovalimab

Participants will be enrolled in three cohorts: [1] Naive Cohort - participants who have not been previously treated with complement inhibitor therapy; [2] Switch Cohort - participants who switch to crovalimab from another C5 inhibitor and [3] Pretreated Cohort (includes C5 SNP (Single Nucleotide Polymorphism) participants) - participants who received treatment with another C5 inhibitor and subsequently discontinued it.

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.

Outcome Measures

Primary Outcome Measures

Percentage of Participants with complete TMA response (cTMAr) (Naive Cohort only) [Baseline up to Week 25]

Secondary Outcome Measures

Dialysis Requirement Status (Yes/No) (Naive and Switch Cohorts) [Baseline up to Week 25]
Observed Value in Estimated Glomerular Filtration Rate (eGFR) (Naive and Switch Cohorts) [Up to 8 years]
Change in Estimated Glomerular Filtration Rate (eGFR) (Naive and Switch Cohorts) [Up to 8 years]
Percentage of Participants with Change from Baseline in Chronic Kidney Disease (CKD) stage (Naive and Switch Cohorts) [Up to 8 years]
Observed Value in Platelet Count (Naive and Switch Cohorts) [Up to 8 years]
Observed Value in Lactate Dehydrogenase (LDH) (mg/dL) (Naive and Switch Cohorts) [Up to 8 years]
Observed Value in Hemoglobin (mg/dL) (Naive and Switch Cohorts) [Up to 8 years]
Change from Baseline in Platelet Count (Naive and Switch Cohorts) [Up to 8 years]
Change from Baseline in Lactate Dehydrogenase (LDH) (mg/dL) (Naive and Switch Cohorts) [Up to 8 years]
Change from Baseline in Hemoglobin (mg/dL) (Naive and Switch Cohorts) [Up to 8 years]
Percentage of Participants with Platelet Count >= LLN (Naive Cohort only) [Baseline up to Week 25]
Percentage of Participants with Normalisation of LDH (i.e., =< ULN) (Naive Cohort only) [Baseline up to Week 25]
Percentage of Participants with >=25% decrease in Serum Creatinine (Naive Cohort only) [Baseline up to Week 25]
Time to complete TMA response (cTMAr) (Naive Cohort only) [Baseline up to Week 25]
Duration of complete TMA response (cTMAr) (Naive Cohort only) [Baseline up to Week 25]
Percentage of Participants with complete TMA response (cTMAr) (Naive Cohort only) [Week 25]
Percentage of Participants with maintained TMA control (mTMAc) (Switch Cohort only) [Baseline through Week 25]
Percentage of Participants with Adverse Events (AEs) [Up to 8 years]
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]
Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation [Up to 8 years]
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 8 years]
Serum Concentrations of Crovalimab over time [Up to 8 years]
Percentage of Participants with Anti-Crovalimab Antibodies [Up to 8 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

28 Days to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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, 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 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 (>= 38oC) within 7 days before the first crovalimab administration.
Multi-system organ dysfunction or failure.
Recent 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).
PE/PI should not be administered within 6 hours of 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 ε (DGKE) nephropathy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Healthcare Systems	Hollywood	Florida	United States	33021
2	Cincinnati Children's Hospital Medical Center; Investigational Drug Services	Cincinnati	Ohio	United States	45229
3	UZ Gent	Gent		Belgium	9000
4	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
5	Santa Casa de Belo Horizonte; Centro de Hemodiálise	Belo Horizonte	MG	Brazil	30150-221
6	UPECLIN Hospital das Clinicas da Faculdade de Medicina de Botucatu	Botucatu	SP	Brazil	18618-686
7	Inst. Da Criança- Faculdade de Medicina Usp; Unidade de Pneumologia	Sao Paulo	SP	Brazil	05403-900
8	CHU Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
9	Peking University First Hospital	Beijing City		China	100034
10	Beijing Children's Hospital, Capital Medical University	Beijing City		China	100045
11	The children's hospital , Zhejiang university school of medicine	Hangzhou City		China	310003
12	Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech	Wuhan		China	430030
13	Hôpital Arnaud de Villeneuve; Néphrologie pédiatrique	Montpellier		France	34295
14	Gh Necker Enfants Malades; Nephrologie	Paris		France	75743
15	Rambam medical Center; Pediatric Nephrology	Haifa		Israel	3109601
16	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Nefrologia Pediatrica	Milano	Lombardia	Italy	20122
17	Aichi Children's Health and Medical Center	Aichi		Japan	474-8710
18	Chiba Children's Hospital	Chibashi, Chibaken		Japan	266-0007
19	Hiroshima Prefectural Hospital	Hiroshima		Japan	734-8530
20	Yokohama City University Medical Center	Kanagawa		Japan	232-0024
21	Okinawa Prefectural Nanbu Medical Center & Children's Medical Center	Okinawa		Japan	901-1193
22	Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadciśnienia Dzieci i Mlodziezy	Gdansk		Poland	80-952
23	Instytut "Centrum Zdrowia Matki Polki; Klinika Pediatrii i Immunologii i Nefrologii	Lodz		Poland	93-338
24	Instytut Pomnik-Centrum Zdrowia Dziecka, Klinika Nefrologii, Transp. Nerek i Nadcisnienia Tetniczego	Warszawa		Poland	04-730
25	Szpital Kliniczny nr 1 im. prof. Szyszko; Oddz. Nefrologii Dzieciecej z Pododdziałem Dializoterapii	Zabrze		Poland	41-800
26	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013

Sponsors and Collaborators

Hoffmann-La Roche
Chugai Pharmaceutical

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT04958265

Other Study ID Numbers:

BO42354
2020-002437-15

First Posted:

Jul 12, 2021

Last Update Posted:

Aug 25, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Azotemia

Hemolytic-Uremic Syndrome

Atypical Hemolytic Uremic Syndrome

Syndrome

Hemolysis

Study Results

No Results Posted as of Aug 25, 2022