CTRI/2021/05/033719 [Registered on: 21/05/2021] Trial Registered Prospectively
Last Modified On:
18/05/2021
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A Clinical Study to Test the Effectiveness and Side Effects of Hetero-Tocilizumab in Rheumatoid
Arthritis Patients
Scientific Title of Study
A Prospective, Randomized, Multiple-Dose, Multi-Center,
Comparative, Parallel Group Clinical Study to Compare the Efficacy, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Safety of Intravenous Injection of Tocilizumab (Hetero Biopharma Limited) and Reference Medicinal Product (Tocilizumab - Roche) Concomitantly Administered with Methotrexate in Patients with Rheumatoid
Arthritis
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
HCR/III/TOCIRA/08/2020; Version 2.0 Dated 09/Dec/2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Hetero Biopharma Limited, H. No. 8-3-166/1,2, 105 to 108, 1st Floor, G Block, EastWing, Challa Estates, Erragadda, Hyderabad, Telangana, India, 500018. Tel No. & Fax No.: 914023810110
Primary Sponsor
Name
Hetero Biopharma Limited
Address
Hetero Biopharma Limited, H. No. 8-3-166/1,2, 105 to 108, 1st Floor, G Block, EastWing, Challa Estates, Erragadda, Hyderabad, Telangana, India, 500018. Tel No. & Fax No.: 914023810110
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 10
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Vishnu Sharma
Avron Hospitals Pvt. Ltd.
Department of Rheumatology, 4, Shantiniketan Park, Nr. Sardar Patel Colony, Naranpura, Ahmedabad-380013, Gujarat Ahmadabad GUJARAT
8511555477
drvishnusharma@yahoo.co.in
Dr Krishnamurthy Venkataraman
Chennai Meenakshi Multispeciality Hospital Ltd.
Department of Rheumatology, Old No. 149, New No. 72, Luz Church Road, Mylapore, Chennai - 600004, Tamilnadu Chennai TAMIL NADU
9841041717
drvk56@gmail.com
Dr S Sham
Gleneagles Global Health City
Department of Rheumatology, No. 439, Cheran Nagar, Perumbakam, Chennai - 600100, Tamil Nadu Chennai TAMIL NADU
9600190790
itsdrsham@gmail.com
Dr Abhishek Arvind Zanwar
Grant Medical foundation Ruby Hall Clinic
Department of Rheumatology, 40, Sassoon Road, Pune - 411001, Maharashtra Pune MAHARASHTRA
9699507339
abhishek.zanwar@gmail.com
Dr Piyush Joshi
Kanoria Hospital & Research Centre
Department of Rheumatology, Airport-Gandhinagar Highway, Village: Bhat
Dist. Gandhinagar- 382428, Gujarat Gandhinagar GUJARAT
8879102056
pnjoshi2005@gmail.com
Dr Rahul Jain
Maharaja Agrasen Superspeciality Hospital
Department of General Medicine, Central Spine, Agrasen Aspatal Marg, Sector- 7, Vidyadhar nagar, Jaipur -302039, Rajasthan Jaipur RAJASTHAN
8826264447
drrahuljain17@gmail.com
Dr Pradeep Kumar
Mazumdar Shaw Medical Centre
Department of Rheumatology, A unit of Narayana Health Care, 258/A Bommasandra Industrial Area, Anekal Taluk, Bangalore- 560099, Karnataka Bangalore KARNATAKA
8747081888
pkharrsha@gmail.com
Dr Romi Kirankumar Shah
Shalby Multi Speciality Hospital
Department of General Medicine, Near Navyug College, Rander Road, Adajan, Surat-395009, Gujarat Surat GUJARAT
8238004052
romi25389@gmail.com
Dr Aradhana Singh
SMS Hospital
Department of General Medicine, Jaipur-302004, Jaipur, Rajasthan Jaipur RAJASTHAN
9166916692
aradhanas610@yahoo.com
Dr Firdaus Fatima
St. Theresa Hospital
Department of Rheumatology, Sanath Nagar, Hyderabad-500018, Telangana Hyderabad TELANGANA
9848315051
cpdstth@gmail.com
Details of Ethics Committee
No of Ethics Committees= 10
Name of Committee
Approval Status
Avron Multispecialty Hospitals Ethics Committee, 4 Shantiniketan Park, Near Sardar Patel Colony, Naranpura, Ahmedabad-380013, Gujarat, ECR/1136/Inst/GJ/2018
Submittted/Under Review
Chennai Meenakshi Multispecialty Hospitals Ethics Committee, Old#149, New#72, Luz Church Road, Mylapore, Chennai-600004, ECR/516/Inst/TN/2014/RR-20
Submittted/Under Review
Ethics Committee, SMS Medical College and attached Hospitals, JLN Marg, Jaipur, Rajastan-302004, ECR/26/Inst/RJ/2013/RR-19
Submittted/Under Review
Ethics Committee, St Theresa Hospital, Sanath Nagar, Hyderabad-500018, ECR/230/Inst/AP/2013/RR-19
Hetero-Tocilizumab
Injection: 80 mg/4 mL (20 mg/mL), 200 mg/10 mL (20
mg/mL), 400 mg/20 mL (20 mg/mL) in single-dose vials for further dilution prior to intravenous infusion
8mg/kg mg will be administered every 4 weeks for 24 weeks with concomitant Methotrexate therapy.
Comparator Agent
RMP-Tocilizumab. Roche Injection: 80 mg/4 mL (20 mg/mL), 200 mg/10 mL (20 mg/mL), 400 mg/20 mL (20 mg/mL) in single-dose vials for further dilution prior to intravenous infusion
8mg/kg mg will be administered every 4 weeks for 24 weeks with concomitant Methotrexate therapy.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Adult male or female patients of age 18 to 65 years (both inclusive)
2. Patients with diagnosis of Active Rheumatoid Arthritis as per the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA score of ≥6 and has a disease duration of at least three months before randomization
3. Patients with Swollen Joint Count (SJC) ≥6 (66 joint count), and Tender Joint Count (TJC) ≥6 (68 joint count) at screening and randomization
4. Patients with erythrocyte sedimentation rate of more than 28mm/hr measured by Westergren method and/or C-reactive protein ≥10 mg/L
5. Patients who are on NSAIDs, must be on a stable dose for at least 8 weeks prior to randomization.
6. The screening laboratory tests must be: Haemoglobin ≥9.0 g/dL, Absolute Neutrophil Count ≥2.0 × 109/L, Platelets ≥100 × 109/L, SGOT and SGPT ≤ ULN, Alkaline phosphatase levels ≤ ULN, Serum creatinine ≤1.5 mg/dL
ExclusionCriteria
Details
1. Patients with known or suspected allergy or
hypersensitivity to Tocilizumab or excipients
2. Patients with functional class IV disease as defined by the American College of Rheumatology (ACR) classification of functional status in RA
3. Patients with history of use of biological disease modifying anti-rheumatic drugs (bDMARDs) within 8 weeks prior to randomization.
4. Patients with history of intra-articular or parenteral corticosteroids use within 8 weeks prior to randomization.
5. Patients with active systemic bacterial, viral, fungal, mycobacterial, or other infections
6. Patients with history of treatment with intravenous antibiotics within 30 days or oral antibiotics within 14 days prior to randomization
7. Patients with history or signs of lymphoproliferative disease
8. Patients who received live or live-attenuated vaccine within 8 weeks prior to randomization
9. Patients participated in an investigational drug study within 8 weeks prior to randomization.
10. Patients with history of blood donation or blood loss of >300ml within 3 months prior to randomization
Method of Generating Random Sequence
Permuted block randomization, fixed
Method of Concealment
On-site computer system
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Proportion of patients with ACR 20 response (≥20%
improvement in the ACR core criteria)
8 weeks and 12
weeks
Secondary Outcome
Outcome
TimePoints
Proportion of patients with ACR 20 response (≥20%
improvement in the ACR core criteria)
24 weeks
Proportion of patients with an ACR 50 and ACR 70
response (≥50%, ≥70% improvement in the ACR core
criteria)
8 weeks, 12 weeks, and 24 weeks
Change from baseline in Disease Activity Score 28
(DAS28-ESR)
8 weeks, 12 weeks, and 24 weeks
Compare the single dose pharmacokinetic parameters of
Cmax, AUC0-t, AUC0-∞
Pre-dose, Post dose at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr, 336 hr, 504 hr and 672 hr after first dose
Compare the treatment emergent adverse events by
monitoring of significant clinical signs and symptoms, and laboratory abnormalities during treatment
All Visits
Target Sample Size
Total Sample Size="210" Sample Size from India="210" 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)
26/05/2021
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
Not Applicable
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is a double blind, randomized, active controlled, parallel group clinical study to compare the efficacy, pharmacokinetics, pharmacodynamics, immunogenicity and safety of intravenous injection of Hetero-Tocilizumab with Reference medicinal product (RMP, Roche) in patients with rheumatoid arthritis. Appropriate number of patients will be enrolled and randomly assigned into two treatment groups in the ratio 2:1 (Hetero-Tocilizumab vs Roche-Tocilizumab). All the patients will be administered either Hetero-Tocilizumab or Roche-Tocilizumab every 4 weeks at 8 mg/kg intravenously. Patients will be administered study drug every 4 weeks for up to a maximum of 24 weeks.