CTRI/2016/07/007097 [Registered on: 15/07/2016] Trial Registered Prospectively
Last Modified On:
14/09/2017
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Multi-centre, randomized, double-blind,
two-arm, parallel group, comparative
clinical study to evaluate pharmacokinetic, efficacy and
safety of Etanercept in Patients with Active
Rheumatoid Arthritis
Scientific Title of Study
Prospective, multi-centre, randomized, double-blind,
two-arm, parallel group, active-control, comparative
clinical study to evaluate pharmacokinetic, efficacy and
safety of R-TPR-018/ Enbrel® in Patients with Active
Rheumatoid Arthritis on a stable dose of Methotrexate
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
RLS/RA/2014/01; Version 1.0, Dated: 03 Nov 2014
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Dr Shashank Deoghare
Designation
Medical Monitor
Affiliation
Reliance Life Sciences Pvt. Ltd.
Address
Reliance Life Sciences Pvt Ltd
Dhirubhai Ambani Life Sciences Centre
Plot R282 TTC Area of MIDC
Thane Belapur Road Rabale
Navi Mumbai
Ethics Committee Chennai Meenakshi Multispeciality Hospital, Chennai Meenakshi Multi-speciality Hospital, Hospital, Old No: 148, New No.72, Luz Church Road, Mylapore, Chennai 600 004, Tamil Nadu, India
Approved
Ethics Committee, Indira Gandhi Govt. Medical College
Approved
Ethics Committee, Sir Ganga ram Hospital
Approved
Institutional Ethics Committee Meenakshi Mission Hospital & Research Centre Lake Area, Melur Road, Madurai 625 107, Tamil Nadu, India
Approved
Institutional Ethics Committee, B. J Government Medical College and Sasoon General Hospitals
Approved
Institutional Ethics Committee, Government Medical College and Hospital
Approved
Institutional Ethics Committee, Jasleen Hospital, Big Bazzar,Panchashil Square, Dhantoli,Nagpur-440012, Maharashtra, India
Approved
Institutional Ethics Committee, Sacheti Institute for Orthopaedics and Rehabilitation, Sacheti Research Centre, 16, Shivaji Nagar, Pune- 411005, Maharashtra, India
Penta-Med Ethics Committee, Medipoint Hospital Pvt. Ltd. 241/1, New D.P. Road, Aundh, Pune- 411007, Maharashtra, India
Approved
Sushruta Hospitals Ethics Committee, C/o Sushruta Multispeciality Hospital & Research Centre Private Limited., P. B. Road, Vidyanagar, Hubli-580021, Karnataka, India.
Approved
Yash Society Institutional Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
In Patients with Active
Rheumatoid Arthritis on a stable dose of Methotrexate,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Enbrel® (Etanercept)and Methotrexate
Strength: 25mg/ml vial
Dose: 50mg
Route: Subcutaneous injection
Frequency: Weekly
Methotrexate:
Dose:10-25mg/week
Duration: 4 weeks prior to screening and for the entire duration of the study
Frequency : weekly
Route of admin: Oral or intramuscular
Intervention
Etanercept coded as R-TPR-018 and Methotrexate
Strength: 25mg/ml vial
Dose: 50 mg
Route: Subcutaneous injection
Frequency: Weekly
Methotrexate:
Dose:10-25mg/week
Duration: 4 weeks prior to screening and for the entire duration of the study
Frequency : weekly
Route of admin: Oral or intramuscular
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Males and females, aged 18 to 65, inclusive.
2. Diagnosis of Rheumatoid Arthritis according to the criteria based on the revised 2010
American College of Rheumatology (ACR)/ European League against Rheumatism
(EULAR) classification criteria for Rheumatoid Arthritis.
3. Subjects must have ACR/EULAR diagnostic criteria score ≥6.
4. Subjects must have active disease as defined by:
a. ≥6 swollen joints
b. ≥6 tender joints and
c. Acute phase reactant values (CRP >8 mg/L or ESR >28 mm/h)
5. Subjects must have been on treatment with methotrexate (10 to 25 mg/week) (oral or
injectable) for at least 3 months with no break(s) in treatment of more than 2 weeks in
total during this period and stable dose between 10 and 25mg/week for at least 4 weeks prior to screening and it is planned that the same dose will continue for the entire duration of the study
6. Subjects using oral corticosteroids must have been on a stable dose of up to 10 mg/day prednisolone or equivalent, for at least 4 weeks prior to screening. If currently not using corticosteroids, the subject must have not received corticosteroids for at least 4 weeks prior to screening.
7. If using NSAIDs [except rofecoxib (Vioxx®) which is not permitted], subjects should have been on a stable dose for at least 4 weeks prior to screening.
8. The screening laboratory tests must meet the following criteria:
• Haemoglobin ≥ 5.0 mmol/L (≥8.0 g/dL).
• WBC ≥3.5 x 109/L
• Neutrophils ≥1.5 x 109/L
• Platelets ≥100 x 109/L
• Serum transaminase ≤2 times the upper limit of normal
• Alkaline phosphatase levels ≤2 times the upper limit of normal
• Serum creatinine ≤150 μmol/L (≤1.7mg/dL)
9. Subjects must be able to adhere to the study visit schedule and other protocol requirements.
10. Subjects must be literate and capable of giving informed consent, and written consent must have been obtained prior to any study procedures.
11. Subjects must have the ability to understand and comply with instructions and be able to complete study-related forms and questionnaires.
12. Men and women of childbearing potential must be using adequate birth control measures, as discussed with the study doctor and should agree to continue such precautions for 6 months after receiving the last injection.
13. Menopausal females must have experienced their last period more than 12 months prior to study entry to be classified as not of childbearing potential.
ExclusionCriteria
Details
1. Pregnant women, nursing mothers or a planned pregnancy within 18 months of randomization.
2. Subjects who are incapacitated, largely or wholly bedridden or confined to a wheelchair, and who have little or no ability for self-care.
3. Subjects who have any current systemic inflammatory condition with signs and symptoms that might confound the evaluations of benefit from the etanercept therapy, e.g., Lyme disease or a rheumatic disease other than Rheumatoid
Arthritis.
4. History within one year prior to randomization of illicit drug use.
5. Prior use of infliximab, adalimumab, certolizumab, golimumab, tocilizumab, rituximab, or etanercept (or any biological treatment of Rheumatoid Arthritis)
6. Prior use of disease-modifying anti-rheumatic drugs, other than methotrexate, including hydroxychloroquine, chloroquine, or sulfasalazine, within 4 weeks prior to screening. Patients who discontinued leflunomide and have had successful chelation with 8g of cholestyramine (3 times daily) for 11 days must wait for 4 weeks prior to screening. Patients who discontinued leflunomide and did not have
cholestyramine washout must wait for 12 weeks after last dose of leflunomide before randomization.
7. Subjects with prior and current use of anakinra or abatacept
8. Subjects with autoimmune disease other than Rheumatoid Arthritis.
9. Subjects must not be on prescription herbal, homeopathic, ayurvedic or traditional medicines, including massage/manipulation therapies for at least 1 month prior to randomization, Subsequently after study medication administration these treatments will be not be allowed throughout study period.
10. Subjects who have a current or past history of chronic infection with Hepatitis B, Hepatitis C, or infection with Human Immunodeficiency Virus-1 or-2 or who have a positive result to the screening test for those infections.
11. History or presence of any form of cancer within the 10 years prior to randomization.
12. Current signs or symptoms of significant, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease that renders the subject incapable of participating in the study
13. History of congestive heart failure [New York Heart Association class III/IV] or
unstable angina.
14. History of lymphoproliferative disease including lymphoma or signs suggestive of
possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic areas), or splenomegaly.
15. Presence of psoriatic arthritis, vasculitis, interstitial lung disease, severe extra articular manifestations or other auto-immune diseases (having documented evidence) except rheumatoid arthritis.
16. Major surgery (including joint surgery) within 12 weeks prior to randomization.
17. History of serious infection, which caused hospitalization within 6 months prior to randomization or other severe or chronic infection (such as sepsis, abscess or opportunistic infections, invasive fungal infection such as histoplasmosis, or a history of recurrent herpes zoster or other chronic or recurrent infection) or a past diagnosis without sufficient documentation of complete resolution following treatment.
18. Pre-existing central nervous system demyelinating disorders.
19. Administration of live or live-attenuated vaccine within 8 weeks of screening.
20. Known allergy to any of the excipients of etanercept.
21. Active tuberculosis. Also excluded are subjects who have evidence of latent tuberculosis [evidence of tuberculosis based on chest X ray, tuberculin skin(Mantoux) test, QuantiFERON®-TB Gold test or other tuberculosis screening tests performed during screening]. Also excluded are subjects with evidence of
an old or latent tuberculosis infection. Subjects with a current close contact with
an individual with active tuberculosis will also be excluded. Additionally, subjects with a household member who has a history of active pulmonary tuberculosis, should have had a thorough evaluation for tuberculosis prior to study enrolment.
Also excluded are subjects with opportunistic infections including, but not limited
to, evidence of active cytomegalovirus, active pneumocystis carinii, aspergillosis, or atypical mycobacterial infection, etc., within the previous 6 months.
22. History or presence of any medical or psychiatric condition or disease, or laboratory abnormality or any other condition that, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation and may prevent the subject from completing the study.
23. Participation in any clinical study of an investigational product within the previous 3 months
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
The primary efficacy endpoint will be the proportion of subjects achieving clinical response
according to the ACR 20 criteria
Week 12
Secondary Outcome
Outcome
TimePoints
Pharmacokinetic parameters assessment after first dose: Cmax, AUC0-t, AUC0-∞, T1/2,
Tmax,Kel
Week 12
ACR20
Week 24
ACR50
Week 12 and Week 24
ACR70
Week 12 and Week 24
Absolute values and changes from baseline in the DAS28
Week 12 and Week 24
Absolute values and changes from baseline in the HAQ-DI
Week 12 and Week 24
Absolute values and changes from baseline in Acute Phase
Reactant.
Week 12 and Week 24
Absolute values and changes from baseline in Rheumatoid
Factor.
Week 12 and Week 24
Safety evaluation - Incidence of adverse events (AEs) and Serious Adverse Events(SAEs)
Week 12 and Week 24
Immunogenicity assessment
Baseline, at 12 Weeks and at 24 Weeks
Target Sample Size
Total Sample Size="105" Sample Size from India="105" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
Prospective, multi-centre, randomized, double-blind, two-arm, parallel group, active-control, comparative clinical study to evaluate efficacy and safety of R-TPR-018/ Enbrel® in Patients with Active Rheumatoid Arthritis on a stable dose of Methotrexate.prospective, multi-centre, randomized, double-blind, two-arm, parallel group, active-control, comparative clinical study to evaluate efficacy and safety of R-TPR-018/ Enbrel® in Patients with Active Rheumatoid Arthritis on a stable dose of Methotrexate.