| CTRI Number |
CTRI/2023/12/060535 [Registered on: 19/12/2023] Trial Registered Prospectively |
| Last Modified On: |
03/07/2024 |
| 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 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
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
400086
India |
| Phone |
9820300215 |
| Fax |
|
| Email |
rupesh.choudhary@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
|
|
|
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
|
|
|
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)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
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. |