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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04861259




Registration number
NCT04861259
Ethics application status
Date submitted
23/04/2021
Date registered
27/04/2021

Titles & IDs
Public title
A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
Scientific 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)
Secondary ID [1] 0 0
2020-002475-35
Secondary ID [2] 0 0
BO42353
Universal Trial Number (UTN)
Trial acronym
COMMUTE-a
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atypical Hemolytic Uremic Syndrome 0 0
Condition category
Condition code
Blood 0 0 0 0
Other blood disorders
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Blood 0 0 0 0
Anaemia
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Crovalimab

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 Complement Component 5 (C5) inhibitor and \[3\] C5 Single Nucleotide Polymorphism (C5 inhibitor) Cohort - participants with documented C5 polymorphism.


Treatment: Drugs: Crovalimab
Crovalimab will be administered at a dose of 1000 milligrams (mg) intravenous (IV) (for participants with body weight at least 40 (\>=) and up to 100 kilograms (kg) 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 subcutaneously (SC). On Week 5 and every 4 weeks (Q4W) thereafter, it will be administered at a dose of 680 mg SC (for participants with body weight \>= 40kg to \<100kg) or 1020 mg SC (for participants with body weight \>=100kg).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Complete Thormbotic Microangiopathy Response (cTMAr)
Timepoint [1] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [1] 0 0
Change from Baseline in Dialysis Status
Timepoint [1] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [2] 0 0
Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)
Timepoint [2] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [3] 0 0
Percentage of Participants with Change from Baseline in Chronic Kidney Disease (CKD) Stage
Timepoint [3] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [4] 0 0
Observed Value in Platelet Count
Timepoint [4] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [5] 0 0
Observed Value in Lactate Dehydrogenase (LDH)
Timepoint [5] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [6] 0 0
Observed Value in Hemoglobin
Timepoint [6] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [7] 0 0
Change from Baseline in Platelet Count
Timepoint [7] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [8] 0 0
Change from Baseline in Lactate Dehydrogenase (LDH)
Timepoint [8] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [9] 0 0
Change from Baseline in Hemoglobin
Timepoint [9] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [10] 0 0
Mean Change From Baseline in Fatigue (in Adult Participants only)
Timepoint [10] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [11] 0 0
Percentage of Participants with Platelet Count >= Lower Limits of Normal (LLN) (Naive Cohort only)
Timepoint [11] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [12] 0 0
Percentage of Participants with Normalization of LDH (i.e. =< Upper Limit of Normal (ULN)) (Naive Cohort only)
Timepoint [12] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [13] 0 0
Percentage of Participants with >=25% Decrease in Serum Creatinine (Naive Cohort only)
Timepoint [13] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [14] 0 0
Time to cTMAr (Naive Cohort only)
Timepoint [14] 0 0
Up to 8 years
Secondary outcome [15] 0 0
Duration of cTMAr (Naive Cohort only)
Timepoint [15] 0 0
Up to 8 years
Secondary outcome [16] 0 0
Percentage of Participants with Ongoing cTMAr (Naive Cohort only)
Timepoint [16] 0 0
At Week 25
Secondary outcome [17] 0 0
Percentage of Participants with Maintained Thrombotic Microangiopathy Control (mTMAc) (Switch Cohort only)
Timepoint [17] 0 0
Baseline up to Week 25 (after 24 weeks on treatment)
Secondary outcome [18] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [18] 0 0
Up to 8 years
Secondary outcome [19] 0 0
Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, Malignant Hypertension (Including Malignant Renal Hypertension) and Infections (Including Meningococcal Meningitis)
Timepoint [19] 0 0
Up to 8 years
Secondary outcome [20] 0 0
Number of Participants with AEs Leading to Study Drug Discontinuation
Timepoint [20] 0 0
Up to 8 years
Secondary outcome [21] 0 0
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
Timepoint [21] 0 0
Up to Week 25
Secondary outcome [22] 0 0
Serum Concentrations of Crovalimab Over Time
Timepoint [22] 0 0
Up to 8 years
Secondary outcome [23] 0 0
Prevalence of Anti-Crovalimab Antibodies at Baseline
Timepoint [23] 0 0
Baseline
Secondary outcome [24] 0 0
Percentage of Participants with Anti-Crovalimab Antibodies
Timepoint [24] 0 0
Up to 8 years
Secondary outcome [25] 0 0
Observed value of Pharmacodynamic Markers (CH50, Free/Total C5)
Timepoint [25] 0 0
Up to 8 years

Eligibility
Key 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).
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)
* 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).
* Diagnosis of 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
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/06/2029
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Brazil
State/province [11] 0 0
MG
Country [12] 0 0
Brazil
State/province [12] 0 0
SP
Country [13] 0 0
Canada
State/province [13] 0 0
British Columbia
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
China
State/province [15] 0 0
Beijing City
Country [16] 0 0
China
State/province [16] 0 0
Beijing
Country [17] 0 0
France
State/province [17] 0 0
Montpellier
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
Germany
State/province [19] 0 0
Essen
Country [20] 0 0
Germany
State/province [20] 0 0
Hannover
Country [21] 0 0
Germany
State/province [21] 0 0
Köln
Country [22] 0 0
Hungary
State/province [22] 0 0
Budapest
Country [23] 0 0
India
State/province [23] 0 0
Delhi
Country [24] 0 0
India
State/province [24] 0 0
Haryana
Country [25] 0 0
India
State/province [25] 0 0
Rajasthan
Country [26] 0 0
Israel
State/province [26] 0 0
Haifa
Country [27] 0 0
Israel
State/province [27] 0 0
Petach Tikva
Country [28] 0 0
Israel
State/province [28] 0 0
Ramat-Gan
Country [29] 0 0
Italy
State/province [29] 0 0
Lazio
Country [30] 0 0
Italy
State/province [30] 0 0
Liguria
Country [31] 0 0
Italy
State/province [31] 0 0
Lombardia
Country [32] 0 0
Italy
State/province [32] 0 0
Toscana
Country [33] 0 0
Japan
State/province [33] 0 0
Aichi
Country [34] 0 0
Japan
State/province [34] 0 0
Mie
Country [35] 0 0
Japan
State/province [35] 0 0
Saitama
Country [36] 0 0
Japan
State/province [36] 0 0
Tokyo
Country [37] 0 0
Mexico
State/province [37] 0 0
Jalisco
Country [38] 0 0
Mexico
State/province [38] 0 0
Mexico CITY (federal District)
Country [39] 0 0
Mexico
State/province [39] 0 0
Nuevo LEON
Country [40] 0 0
Mexico
State/province [40] 0 0
Sinaloa
Country [41] 0 0
New Zealand
State/province [41] 0 0
Auckland
Country [42] 0 0
New Zealand
State/province [42] 0 0
Christchurch
Country [43] 0 0
New Zealand
State/province [43] 0 0
Dunedin
Country [44] 0 0
Peru
State/province [44] 0 0
Bellavista
Country [45] 0 0
Peru
State/province [45] 0 0
Lima
Country [46] 0 0
Poland
State/province [46] 0 0
Gdansk
Country [47] 0 0
Poland
State/province [47] 0 0
Lodz
Country [48] 0 0
Poland
State/province [48] 0 0
Warszawa
Country [49] 0 0
Poland
State/province [49] 0 0
Zabrze
Country [50] 0 0
South Africa
State/province [50] 0 0
Rondebosch
Country [51] 0 0
South Africa
State/province [51] 0 0
Umkumbaan
Country [52] 0 0
Spain
State/province [52] 0 0
LA Coruña
Country [53] 0 0
Spain
State/province [53] 0 0
Barcelona
Country [54] 0 0
Spain
State/province [54] 0 0
Madrid
Country [55] 0 0
Spain
State/province [55] 0 0
Sevilla
Country [56] 0 0
Turkey
State/province [56] 0 0
Istanbul
Country [57] 0 0
Turkey
State/province [57] 0 0
Kayseri
Country [58] 0 0
Turkey
State/province [58] 0 0
Kocaeli
Country [59] 0 0
Turkey
State/province [59] 0 0
Konya
Country [60] 0 0
Turkey
State/province [60] 0 0
Malatya
Country [61] 0 0
Turkey
State/province [61] 0 0
Samsun

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Chugai Pharmaceutical
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: BO42353 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04861259