Multi-centre, randomized, double-blind,two-arm, parallel group, comparativeclinical study to evaluate pharmacokinetic, efficacy andsafety of Etanercept in Patients with ActiveRheumatoid Arthritis
Phase 3
Active, not recruiting
- Conditions
- In Patients with ActiveRheumatoid Arthritis on a stable dose of Methotrexate
- Registration Number
- CTRI/2016/07/007097
- Lead Sponsor
- Reliance Life Sciences Pvt Ltd
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- All
- Target Recruitment
- 105
Inclusion Criteria
- Males and females, aged 18 to 65, inclusive.
- 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.
- Subjects must have ACR/EULAR diagnostic criteria score ≥6.
- 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.
- 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.
- 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.
- Subjects must be literate and capable of giving informed consent, and written consent must have been obtained prior to any study procedures.
- Subjects must have the ability to understand and comply with instructions and be able to complete study-related forms and questionnaires.
- 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.
- Menopausal females must have experienced their last period more than 12 months prior to study entry to be classified as not of childbearing potential.
Exclusion Criteria
- Pregnant women, nursing mothers or a planned pregnancy within 18 months of randomization.
- Subjects who are incapacitated, largely or wholly bedridden or confined to a wheelchair, and who have little or no ability for self-care.
- 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.
- History within one year prior to randomization of illicit drug use.
- 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.
- Subjects with prior and current use of anakinra or abatacept 8.
- Subjects with autoimmune disease other than Rheumatoid Arthritis.
- 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.
- 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.
- History or presence of any form of cancer within the 10 years prior to randomization.
- 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.
- 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.
- Presence of psoriatic arthritis, vasculitis, interstitial lung disease, severe extra articular manifestations or other auto-immune diseases (having documented evidence) except rheumatoid arthritis.
- Major surgery (including joint surgery) within 12 weeks prior to randomization.
- 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.
- Pre-existing central nervous system demyelinating disorders.
- Known allergy to any of the excipients of etanercept.
- Active tuberculosis.
- 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.
- 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.
- Participation in any clinical study of an investigational product within the previous 3 months.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary efficacy endpoint will be the proportion of subjects achieving clinical response Week 12 according to the ACR 20 criteria Week 12
- Secondary Outcome Measures
Name Time Method Pharmacokinetic parameters assessment after first dose: Cmax, AUC0-t, AUC0-∞, T1/2, Tmax,Kel Absolute values and changes from baseline in the DAS28 Week 12 and Week 24 Safety evaluation - Incidence of adverse events (AEs) and Serious Adverse Events(SAEs) Week 12 and Week 24 Absolute values and changes from baseline in Rheumatoid Factor. ACR20 Week 24 ACR50 Week 12 and Week 24 ACR70 Week 12 and Week 24 Absolute values and changes from baseline in Acute Phase Reactant. Absolute values and changes from baseline in the HAQ-DI Week 12 and Week 24 Immunogenicity assessment Baseline, at 12 Weeks and at 24 Weeks
Trial Locations
- Locations (13)
B. J Government Medical College and Sasoon General Hospitals
🇮🇳Pune, MAHARASHTRA, India
Government Medical College and Hospital
🇮🇳Nagpur, MAHARASHTRA, India
Indira Gandhi Govt. Medical College
🇮🇳Nagpur, MAHARASHTRA, India
Jasleen Hospital
🇮🇳Nagpur, MAHARASHTRA, India
Medipoint Hospital
🇮🇳Pune, MAHARASHTRA, India
Meenakshi Mission Hospital & Research Centre
🇮🇳Madurai, TAMIL NADU, India
Oyster & Pearl Hospital
🇮🇳Pune, MAHARASHTRA, India
Sancheti Institute for Orthopeadics & Rehabilitation
🇮🇳Pune, MAHARASHTRA, India
Shalby Hospitals
🇮🇳Ahmadabad, GUJARAT, India
Sir Ganga Ram Hospital
🇮🇳Delhi, DELHI, India
Scroll for more (3 remaining)B. J Government Medical College and Sasoon General Hospitals🇮🇳Pune, MAHARASHTRA, IndiaDr Amit KalePrincipal investigatordrkalea@gmail.com