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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04861259

Collaborator

Chugai Pharmaceutical (Industry)

Enrollment

Locations

Arm

68.1

Anticipated Duration (Months)

1.6

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 adult and adolescent participants with aHUS.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 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 Adult and Adolescent Patients With Atypical Hemolytic Uremic Syndrome (aHUS)

Actual Study Start Date :

Oct 22, 2021

Anticipated Primary Completion Date :

Mar 8, 2024

Anticipated Study Completion Date :

Jun 25, 2027

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] C5 SNP (Single Nucleotide Polymorphism) Cohort - participants with documented C5 polymorphism.	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).

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] C5 SNP (Single Nucleotide Polymorphism) Cohort - participants with documented C5 polymorphism.

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).

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Dialysis Requirement Status (Yes/No) [Baseline up to Week 25]
Observed Value in Estimated Glomerular Filtration Rate (eGFR) [Up to 7 years]
Change in Estimated Glomerular Filtration Rate (eGFR) [Up to 7 years]
Percentage of Participants with Change from Baseline in Chronic Kidney Disease (CKD) stage [Up to 7 years]
Observed Value in Platelet Count [Up to 7 years]
Observed Value in Lactate Dehydrogenase (LDH) (mg/dL) [Up to 7 years]
Observed Value in Hemoglobin (mg/dL) [Up to 7 years]
Change from Baseline in Platelet Count [Up to 7 years]
Change from Baseline in Lactate Dehydrogenase (LDH) (mg/dL) [Up to 7 years]
Change from Baseline in Hemoglobin (mg/dL) [Up to 7 years]
Mean Change in Fatigue [Up to 7 years]
Assessed by the FACIT-Fatigue Questionnaire.
Percentage of Participants with Platelet Count >= LLN (Naive Cohort only) [Baseline up to Week 25]
Percentage of Participants with Normalization 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 7 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 7 years]
Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation [Up to 7 years]
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 7 years]
Serum Concentrations of Crovalimab over time [Up to 7 years]
Percentage of Participants with Anti-Crovalimab Antibodies [Up to 7 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 receiving other therapies (e.g., immunosuppressants, corticosteroids, mTORi, or calcineurin inhibitors: stable dose for 28 days.
For female participants of childbearing potential: an agreement to remain abstinent or use contraception.
Female patients 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 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) not 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 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 Diacylglycerol kinase ε (DGKE) nephropathy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Irvine Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
2	Memorial Healthcare Systems	Hollywood	Florida	United States	33021
3	Harvard Institutes of Medicine	Boston	Massachusetts	United States	02115
4	Washington University	Saint Louis	Missouri	United States	63128
5	SUNY at Stony Brook	Stony Brook	New York	United States	11790
6	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
7	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43212
8	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
9	Santa Casa de Misericordia; de Belo Horizonte	Belo Horizonte	MG	Brazil	30150-221
10	UPECLIN Hospital das Clinicas da Faculdade de Medicina de Botucatu	Botucatu	SP	Brazil	18618-686
11	Hospital das Clinicas - FMUSP	Sao Paulo	SP	Brazil	05403-900
12	Hospital Samaritano	São Paulo	SP	Brazil	01232-010
13	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1L8
14	St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
15	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
16	Beijing Children's Hospital, Capital Medical University	Beijing City		China	100045
17	Peking University First Hospital; NEPHROLOGY	Beijing		China	100034
18	Hopital Lapeyronie; Nephrologie	Montpellier		France	34295
19	Hôpital Arnaud de Villeneuve; Néphrologie pédiatrique	Montpellier		France	34295
20	Hôpital Robert Debré; Nephrologie pediatrique	Paris		France	75019
21	Gh Necker Enfants Malades; Nephrologie	Paris		France	75743
22	Hopital Tenon; Service SINRA	Paris		France	75970
23	Universitätsklinikum Essen; Klinik für Kinder- und Jugendmedizin Pädiatrie II	Essen		Germany	45122
24	Klinik für Nephrologie des Universitätsklinikum Essen; Klinik für Infektiologie - MFZ	Essen		Germany	45147
25	Medizinische Hochschule Hannover; Klinik für Nieren- und Hochdruckerkrankungen	Hannover		Germany	30625
26	Klinik II für Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin	Köln		Germany	50937
27	Del- Pesti Centrumkorhaz- Szent Laszlo Korhaz Telephely	Budapest		Hungary	1097
28	Rambam Medical Center; Department of Nephrology and Hypertension	Haifa		Israel	3109601
29	Rabin Medical Center; Nephrology	Petach Tikva		Israel	0049100
30	Sheba MC; Nephrology	Ramat-Gan		Israel	5262000
31	A.O. Universitaria S. Martino Di Genova; Nefrologia	Genova	Liguria	Italy	16132
32	Presidio Ospedaliero Maggiore Policlinico Fondazione IRCCS; Pad Croff Div Nefrologia Dialisi	Milano	Lombardia	Italy	20122
33	Az. Osp. Careggi; Reparto Di Nefrologia, Dialisi E Trapianti	Firenze	Toscana	Italy	50139
34	Nagoya University Hospital	Aichi		Japan	466-8560
35	Mie University Hospital	Mie		Japan	514-8507
36	Saitama Medical University Hospital	Saitama		Japan	350-0451
37	The University of Tokyo Hospital	Tokyo		Japan	113-8655
38	Hospital General de México	Distrito Federal	Mexico CITY (federal District)	Mexico	06726
39	Centro para el Desarrollo de la Medicina y de Asistencia	Culiacán Rosales	Sinaloa	Mexico	80230
40	Instituto Nacional de Ciencias; Medicas y Nutricion; Salvador Zubiran	Mexico, Distrito Federal		Mexico	14000
41	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey		Mexico	64460
42	Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion	Bellavista		Peru	Callao 2
43	Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadciśnienia Dzieci i Mlodziezy	Gdansk		Poland	80-952
44	Instytut "Centrum Zdrowia Matki Polki; Klinika Pediatrii i Immunologii i Nefrologii	Lodz		Poland	93-338
45	Szpital Kliniczny nr 1 im. prof. Szyszko; Oddz. Nefrologii Dzieciecej z Pododdziałem Dializoterapii	Zabrze		Poland	41-800
46	Inkosi Albert Luthuli Central Hospital; Pediatric Nephrology	Umkumbaan		South Africa	4091
47	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Nefrologia	La Coruna	LA Coruña	Spain	15006
48	Hospital Clinic i Provincial; Servicio de Nefrologia	Barcelona		Spain	08036
49	Hospital Universitario 12 de Octubre; Servicio de Nefrologia	Madrid		Spain	28041
50	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
51	Istanbul University Istanbul Medical Faculty; Department of Internal Medicine	Istanbul		Turkey	34390
52	Erciyes University Medical Faculty; Internal Medicine	Kayseri		Turkey	38039
53	Kocaeli University Medical Faculty	Kocaeli		Turkey	41380
54	Necmettin Erbakan University Meram Medical Faculty ; Internal Diseases	Konya		Turkey	42080
55	Inonu University Faculty of Medicine Turgut Ozal Medical Center	Malatya		Turkey	44280
56	Ondokuz Mayis Univ. Med. Fac.	Samsun		Turkey	55139

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:

NCT04861259

Other Study ID Numbers:

BO42353
2020-002475-35

First Posted:

Apr 27, 2021

Last Update Posted:

Jul 21, 2022

Last Verified:

Jul 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 Jul 21, 2022