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A Clinical Trial to Study the Effects of Revamilast in Patients With Rheumatoid Arthritis

Phase 2
Completed
Conditions
Rheumatoid Arthritis
Interventions
Drug: Placebo Comparator
Registration Number
NCT01430507
Lead Sponsor
Glenmark Pharmaceuticals Ltd. India
Brief Summary

Rheumatoid arthritis (RA) is a systemic autoimmune and chronic inflammatory disease that causes progressive damage to joints of the body, affecting the functional capacity. Effective management of patients with RA requires a multidisciplinary approach. Despite the various combinations, there is a significant population of RA patients who are not responding to these combinations or showing inadequate response to methotrexate alone. Hence, there is a need for a unique combination of drugs targeting different pathological process to yield the best results in those patients where prognosis is poor. Combination of revamilast with first line therapy like methotrexate could provide better treatment options to a larger population of RA patients having moderate to severe disease and who are inadequately controlled on one or the other DMARDs.

This is randomized, double-blind, placebo-controlled, parallel group study. The study will include patients with active RA receiving stable and maximum tolerated dose of MTX.

Patients will be recruited after providing written informed consent. After screening and run in period (single blind placebo for 4 weeks), patients will be randomized (meeting randomization criteria) in 1:2:2:2 ratios to receive either one of three doses (Low, Medium and High) of revamilast or placebo along with MTX.

The primary objective of the study is to determine the percentage of patients achieving ACR20 response at 12 weeks. Secondary objectives include determining percentage of patients with ACR50 and ACR70 response, change in DAS-28 score, change in serum CRP and ESR values and frequency and use of rescue medication.

During the treatment period, there will be 5 further study visits at week 2, week 4, week 8, week 12, for efficacy, safety and tolerability assessment and visit at week 14 will be follow up visit.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
406
Inclusion Criteria
  1. Male or female ≥18 to ≤ 65 years of age

  2. Documented history of RA; diagnosed according to the revised American College of Rheumatology criteria (ACR)

  3. Active RA defined as patients with:

    • 6 swollen joint counts

    • 6 tender/painful joint counts, and

      • At least two of the three following criteria:

        • Rheumatoid Factor positive or Anti CCP positive
        • CRP ≥1.2 times upper limit of normal reference range or ESR >28 mm/hr
        • Morning stiffness lasting >45 min for at least last4 weeks
  4. DAS-28 CRP values ≥ 4.5 at screening (visit 1)

  5. Patients must have been on stable (15 mg to 25 mg) or maximum tolerated dose of MTX for at least 12 weeks prior to screening

  6. The patient's written informed consent to participate in the study

  7. Female participants must have a negative serum pregnancy test at screening visit.

  8. Males must agree to use barrier while on study medication and for 90 days after taking the last dose of study medication

  9. Must meet the following laboratory criteria:

    • Hemoglobin ≥ 9 g/dL
    • White blood cell (WBC) count; ≥3.0 X 109/L
    • Platelet count ≥ 100,000 /L (100 X 109/L)
    • Serum creatinine <1.5 mg/dL (or 133mol/L)
    • Total bilirubin <2.0 mg/dL
    • AST & ALT<1.5 times upper limit of normal
Exclusion Criteria
  1. Diagnosis of RA prior to 16 years of age (Juvenile RA)
  2. Non-degenerative joint diseases or other joint diseases that could interfere with the evaluation of RA
  3. Patients with any other autoimmune rheumatic disorders with the exception of Sjogren's syndrome.
  4. Patients with first degree relative with immune deficiency
  5. History of infection with human immunodeficiency virus and/or active hepatitis B or C
  6. Severe disabling arthritis leaving the patient eligible for surgical intervention, or incapacitated and prostrated patients
  7. Patients with a history of drug or alcohol abuse or chronic smoking
  8. Uncontrolled diabetes mellitus
  9. Concurrent diseases that might interfere with the conduct of the study,
  10. ECG abnormalities judged by the investigator to be clinically significant
  11. History of using any other test drug, one month before the beginning of this trial
  12. Women who are pregnant or breast-feeding or on hormonal therapy
  13. Patients who in the Investigator's opinion might not be suitable for the study.
  14. Patients with a life expectancy of less than 1 year

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo ComparatorMatching Placebo in Triple Dummy Format
Low doseRevamilastLow dose Revamilast
Medium DoseRevamilastMedium Dose Revamilast
High DoseRevamilastHigh Dose Revamilast
Primary Outcome Measures
NameTimeMethod
Percentage of patients achieving ACR20 response12 weeks
Secondary Outcome Measures
NameTimeMethod
Change in DAS-28 scoreweek 12
Change in serum CRP and ESR values12 weeks
Frequency and use of rescue medication12 weeks
Percentage of patients achieving ACR50 and ACR 70 response12 weeks

Trial Locations

Locations (36)

M S Ramaiah Medical College and Hospital

🇮🇳

Bangalore, Karnataka, India

Oddział Kliniczny Reumatologii i Ukladowych Chorob Tkanki Lacznej

🇵🇱

Bydgoszcz, Wojewodztwo kujawsko pomorskie, Poland

NZOZ Reumed

🇵🇱

Lublin, Wojewodztwo lubelskie, Poland

Niepubliczny Zaklad Opieki Zdrowotnej Medica Pro Familia Sp. z o.o.

🇵🇱

Warszawa, Wojewodztwo lubelskie, Poland

Chennai Meenakshi Multispeciality Hospital Limited

🇮🇳

Chennai, Tamil Nadu, India

Queen's Hospital

🇬🇧

Romford, Essex, United Kingdom

Mahavir Hospital and Research Center

🇮🇳

Hyderabad, Andhra Pradesh, India

Advance Rheumatology Clinic

🇮🇳

Hyderabad, Andhra Pradesh, India

Sri Deepti Rheumatology Center

🇮🇳

Hyderabad, Andhra Pradesh, India

Krishna Institute of Medical Sciences

🇮🇳

Secunderabad, Andhra Pradesh, India

Centre for Knee & Hip Surgery

🇮🇳

Vadodara, Gujarat., India

Chanre Rheumatology and Immunology centre and Research

🇮🇳

Bangalore, Karnataka, India

Sushrut Hospital Research Centre and PG Institute of Orthopaedics

🇮🇳

Nagpur, Maharashtra, India

Rathi Orthopaedic & Research Center

🇮🇳

Ahmedabad, Gujarat, India

Shalby Hospitals

🇮🇳

Ahmedabad, Gujarat, India

Kennisha Rheumatology Care & Diagnostics

🇮🇳

Mumbai, Maharashtra, India

Vidarbha Arthritis & Superspeciality Clinic

🇮🇳

Nagpur, Maharashtra, India

Sanjay Gandhi Postgraduate Institute of Medical Sciences

🇮🇳

Lucknow, Uttar Pradesh, India

Chhatrapati Shahuji Maharaj Medical University

🇮🇳

Lucknow, Uttar Pradesh, India

Brokenshire Memorial Hospital

🇵🇭

Davao City, Davao, Philippines

University of Perpetual Help Dalta Medical Center

🇵🇭

Las Pinas City, Metro Manila, Philippines

Institute of Post Graduate Medical Education & Research (IPGMER)

🇮🇳

Kolkata, West Bengal, India

Manila Doctors Hospital

🇵🇭

Manila, Metro Manila, Philippines

St. Luke's Medical Center

🇵🇭

Quezon City, Metro Manila, Philippines

University of Santo Tomas Hospital

🇵🇭

Manila, Metro Manila, Philippines

Internal Medicine and Rheumatology, Chong Hua Hospital

🇵🇭

Cebu, Philippines

Department of Medicine, Davao Doctor's Hospital

🇵🇭

Davao, Philippines

Osrodek Badan Klinicznych Prof. Dr hab. med.

🇵🇱

Lublin, Wojewodztwo lubelskie, Poland

Centrum Medyczne MEDENS S.C. Grupowa Praktyka Lekarska

🇵🇱

Chelm Slaski, Wojewodztwo slaskie, Poland

Specjalistyczna Praktyka Lekarska Joanna Badowska

🇵🇱

Czestochowa, Wojewodztwo slaskie, Poland

Teaching Hospital Karapitiya

🇱🇰

Galle, Colombo, Sri Lanka

National Hospital of Sri Lnka

🇱🇰

Colombo, Sri Lanka

Wojewodzki Zespol Specjalistycznej Opieki Zdrowotnej

🇵🇱

Wroclaw, Wojewodztwo slaskie, Poland

Colombo South Teaching Hospital

🇱🇰

Colombo, Sri Lanka

Nawaloka Hospitals PLC

🇱🇰

Colombo, Sri Lanka

The Leeds Teaching Hosptial NHS Trust, Chapel Allerton Hospital

🇬🇧

Leeds, Yorkshire, United Kingdom

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