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CTRI Number  CTRI/2023/12/060590 [Registered on: 20/12/2023] Trial Registered Prospectively
Last Modified On: 08/07/2024
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 childrens aged more than 28 days to less than 18 years. 
Scientific Title of Study   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) 
Trial Acronym  Commute-p 
Secondary IDs if Any  
Secondary ID  Identifier 
BO42354_Version 3_dated 08April2022  Protocol Number 
NCT04958265  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

Mumbai
MAHARASHTRA
400086
India 
Phone  91-9820006317  
Fax    
Email  viraj.suvarna@roche.com  
 
Details of Contact Person
Public Query
Modification(s)  
Name  Rupesh Choudhary 
Designation  Manager - 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

Mumbai
MAHARASHTRA
400086
India 
Phone  9820300215  
Fax    
Email  rupesh.choudhary@roche.com  
 
Source of Monetary or Material Support  
F HoffmannLa Roche Ltd Grenzacherstrasse 124, CH-4070 Basel, Switzerland 
 
Primary Sponsor  
Name  F HoffmannLa Roche Ltd 
Address  Grenzacherstrasse 124, CH-4070 Basel, Switzerland 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
Roche Products India Pvt Ltd  146-B, 166 A, Unit No. 7, 8, 9 8th Floor, R City Office, R City Mall Lal Bahadur Shastri Marg Ghatkopar, Mumbai 
 
Countries of Recruitment     Belgium
Brazil
Canada
China
France
Hungary
India
Israel
Italy
Japan
Poland
South Africa
Spain
United States of America  
Sites of Study
Modification(s)  
No of Sites = 2  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Aditi Sinha   All India Institute of Medical Sciences  Department of Pediatrics, #802, A Wing Eighth Floor Mother And Child Block, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, Delhi, 110029
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, Haryana
Gurgaon
HARYANA 		 9868306235

sidsdoc@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 2  
Name of Committee  Approval Status 
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: Body Weight more than equal to 12 kg to less than 20 kg  Crovalimab Loading Dose Day 1: 200 mg IV Day 2: 85 mg SC Weeks 2, 3, and 4 85 mg SC weekly Crovalimab Maintenance Doses: Week 5 and until study completion 170 mg SC every 2 weeks  
Intervention  Crovalimab: Body Weight more than equal to 5kg to less than 12kg  Crovalimab Loading Dose: Week 1:- Day 1: 100 mg IV Day 2: 85 mg SC Crovalimab Maintenance Doses: Week 3 and until study completion 85 mg SC Q2W  
Intervention  Crovalimab: Body Weight more than equal to 100 kg   Crovalimab Loading Dose: Week 1 Day 1: 1500 mg IV Day 2: 340 mg SC Weeks 2, 3, and 4 340 mg SC weekly Crovalimab Maintenance Doses: Week 5 and until study completion 1020 mg SC every 4 weeks  
Intervention  Crovalimab: Body Weight more than equal to 20 kg to less than 30 kg  Crovalimab Loading Dose Week 1 Day 1: 300 mg IV Day 2: 85 mg SC Weeks 2, 3 and 4 85 mg SC weekly Crovalimab Maintenance Doses: Week 5 and until study completion 340 mg SC every 4 weeks  
Intervention  Crovalimab: Body Weight more than equal to 30 kg to less than 40 kg  Crovalimab Loading Dose: Week 1 Day 1: 400 mg IV Day 2: 170 mg SC Weeks 2, 3, and 4 170 mg SC weekly Crovalimab Maintenance Doses: Week 5 and until study completion 510 mg SC every 4 weeks  
Intervention  Crovalimab: Body Weight more than equal to 40 kg to less than 100 kg  Crovalimab Loading Dose: Week 1 Day 1: 1000 mg IV Day 2: 340 mg SC Weeks 2, 3, and 4 340 mg SC weekly Crovalimab Maintenance Doses: Week 5 and until study completion 680 mg SC every 4 weeks  
Comparator Agent  Not Applicable  It is an open label study and there is no comparator. 
 
Inclusion Criteria  
Age From  28.00 Day(s)
Age To  18.00 Year(s)
Gender  Both 
Details  Body weight more than 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 participants receiving other therapies (e.g. immunosuppressants, corticosteroids, mTORi, or calcineurin inhibitors: stable dose for more than 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).
 
 
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 (more than 38 degrees celsius) 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/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.
 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Percentage of Participants with complete TMA response (cTMAr) (Naive Cohort only)  Upto 25 weeks 
 
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 8 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="30"
Sample Size from India="6" 
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)   30/01/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  14/12/2021 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="8"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Open to Recruitment 
Recruitment Status of Trial (India)  Closed to Recruitment of Participants 
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   BO42354 is a single arm, multicenter, global Phase III study designed to evaluate the efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics of Crovalimab in patients with aHUS, aged more than 28 days to less than 18 years, and weighing more than 5 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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