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CTRI Number  CTRI/2023/12/060535 [Registered on: 19/12/2023] Trial Registered Prospectively
Last Modified On: 11/01/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Single Arm Study 
Public Title of Study   Clinical trial study for atypical hemolytic uremic syndrome in adult & adolescent patients.  
Scientific Title of Study   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) 
Trial Acronym  Commute 
Secondary IDs if Any  
Secondary ID  Identifier 
BO42353_Version 4_dated08April2022  Protocol Number 
NCT04861259  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Sidharth Kumar Sethi 
Designation  Senior Consultant - Nephrology & Kidney Transplant Medicine 
Affiliation  Medanta The Medicity 
Address  Kidney & Urology Institute, 12 Floor Room No 21 Sector -38, CH Bhaktawar Singh Road, Gurgaon, Haryana

Gurgaon
HARYANA
122001
India 
Phone  91-9868306235  
Fax    
Email  sidsdoc@gmail.com  
 
Details of Contact Person
Scientific Query

Modification(s)  
Name  Dr Viraj Suvarna 
Designation  Chief Medical Officer 
Affiliation  Roche Products (India) Pvt. Ltd.  
Address  146-B, 166 A, Unit No. 7, 8, 9 8th Floor, R City Office, R City Mall Lal Bahadur Shastri Marg Ghatkopar

Mumbai
MAHARASHTRA
400086
India 
Phone  91-9820006317  
Fax    
Email  viraj.suvarna@roche.com  
 
Details of Contact Person
Public Query
 
Name  Ms Priyanka Bhattacharya  
Designation  Lead-Clinical Operations 
Affiliation  Roche Products India Private Limited  
Address  146-B, 166 A, Unit No. 7, 8, 9 8th Floor, R City Office, R City Mall Lal Bahadur Shastri Marg Ghatkopar

Mumbai
MAHARASHTRA
400086
India 
Phone  91-8879099480  
Fax    
Email  priyanka.bhattacharya@roche.com  
 
Source of Monetary or Material Support  
F HoffmannLa Roche Ltd, CH-4070 Basel, Switzerland  
 
Primary Sponsor  
Name  Roche Products India Pvt Ltd 
Address  146-B, 166 A, Unit No. 7, 8, 9 8th Floor, R City Office, R City Mall Lal Bahadur Shastri Marg Ghatkopar, Mumbai  
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Belgium
Brazil
Canada
China
France
Germany
Hungary
India
Israel
Italy
Japan
Mexico
Peru
Poland
South Africa
Spain
Turkey
United States of America  
Sites of Study
Modification(s)  
No of Sites = 3  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Aditi Sinha  All India Institute of Medical Sciences  #802, Department of Pediatrics. Eight floor, Mother and Child block, All India institute of Medical Sciences, Ansari Nagar , New Delhi 110029, India
New Delhi
DELHI 
9899145489

aditisinhaaiims@gmail.com 
Dr Sidharth Kumar Sethi  Medanta The Medicity  Kidney & Urology Institute, 12 Floor Room No 21 Sector 38, CH Bhaktawar Singh Road, Gurugram 122001
Gurgaon
HARYANA 
9868306235

sidsdoc@gmail.com 
Dr Dhananjai Agrawal  Sawai Man Singh (SMS) Superspeciality Hospital  Attached to SMS Medical College, Vivekanand Marg, C-Scheme, Jaipur-302001, Rajasthan
Jaipur
RAJASTHAN 
9414459790

dhananjaynephro@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 3  
Name of Committee  Approval Status 
Ethics Committee - S.M.S Medical College and Attached Hospitals, Jaipur  Approved 
Institute Ethics Committee - AIIMS  Approved 
Medanta Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: D593||Hemolytic-uremic syndrome,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Crovalimab IV  Dose: 340 mg IV ; Frequency: A loading series will include an initial IV crovalimab dose on Week 1 Day 1 ; Duration: 3 years 
Intervention  Crovalimab SC  Dose: 340 mg SC; Frequency: A loading series will include an initial IV crovalimab dose on Week 1 Day 1 followed by four once weekly SC crovalimab doses on Week 1 Day 2, then on Weeks 2, 3, and 4. Maintenance dosing will begin at Week 5 and will continue Q4W thereafter, for a total of at least 24 weeks of crovalimab treatment. To collect long-term safety and efficacy data, after completing 24 weeks of treatment with crovalimab (i.e., at the Week 25 visit), patients who derive clinical benefit may continue to receive crovalimab during the extension period of the study (which may last for a maximum of 3 years after the last patient has completed the primary treatment period [i.e., Week 25 visit]); Duration: 3 years 
Comparator Agent  Not Applicable  Not Applicable as it is open label and there is no comparator 
 
Inclusion Criteria  
Age From  12.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  Body weight 40 kg above 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). 
 
ExclusionCriteria 
Details  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 (38 degree Celcius above) 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. 
 
Method of Generating Random Sequence    
Method of Concealment    
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Percentage of Participants with complete TMA response (cTMAr)   Baseline up to Week 25  
 
Secondary Outcome  
Outcome  TimePoints 
Naive and Switch Cohort:
Dialysis requirement status, change from baseline to Week 25

Observed value and change from baseline in estimated glomerular filtration rate (eGFR)

Proportion of patients with change from baseline in CKD stage, classified as improved, stable (no change), or worsened based on the National Kidney Foundation Chronic Kidney Disease Stage

Observed value and change from baseline in hematologic parameters (platelet count, LDH, hemoglobin)
 
upto 7 years 
Naive Cohort Only:
Proportion of patients with platelet count more than LLN at two separate assessments, obtained at least 4 weeks (28 days) apart, by Week 25
Proportion of patients with normalization of LDH (i.e., less than ULN) at two separate assessments, obtained at least 4 weeks (28 days) apart, by Week 25
Proportion of patients with more than 25% decrease in serum creatinine from baseline, confirmed at two separate assessments, obtained at least 4 weeks (28 days) apart, by Week 25
Time to cTMAr
Duration of cTMAr, among patients who achieved cTMAr
Proportion of patients with cTMAr at Week 25
 
Baseline up to Week 25  
Switch Cohort:
Proportion of patients with maintained TMA control (mTMAc) from baseline through Week 25 (after 24 weeks on treatment)
 
Baseline up to Week 25  
 
Target Sample Size   Total Sample Size="90"
Sample Size from India="12" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   20/12/2023 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  22/10/2021 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="7"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Open to Recruitment 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   Not applicable at present 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   BO42353 is a single-arm, uncontrolled, multicenter, global Phase III study designed to evaluate the efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics of Crovalimab in patients with aHUS, aged more than 12 years, and weighing more than 40 kg. Patients will be enrolled in three parallel cohorts, based on their previous exposure and response to complement inhibitor therapy. All cohorts will contribute to PK and safety evaluations of Crovalimab.  
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