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

This study has been completed.
Sponsor:
Collaborator:
Glenmark Pharmaceuticals SA
Information provided by (Responsible Party):
Glenmark Pharmaceuticals Ltd. India
ClinicalTrials.gov Identifier:
NCT01430507
First received: September 7, 2011
Last updated: December 27, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Revamilast
Drug: Placebo Comparator
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIb, 12 Week Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Evaluate Efficacy, Safety and Tolerability of Revamilast in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate

Resource links provided by NLM:


Further study details as provided by Glenmark Pharmaceuticals Ltd. India:

Primary Outcome Measures:
  • Percentage of patients achieving ACR20 response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of patients achieving ACR50 and ACR 70 response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in DAS-28 score [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Change in serum CRP and ESR values [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Frequency and use of rescue medication [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 406
Study Start Date: September 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Medium Dose
Medium Dose Revamilast
Drug: Revamilast
Tablet, Medium dose, Once daily for 12 weeks
Experimental: High Dose
High Dose Revamilast
Drug: Revamilast
Tablet, High dose, Once daily for 12 weeks
Placebo Comparator: Placebo
Matching Placebo in Triple Dummy Format
Drug: Placebo Comparator
Matching Placebo in triple dummy format, Tablet, Once daily for 12 weeks
Experimental: Low dose
Low dose Revamilast
Drug: Revamilast
Tablet, Low dose, Once daily for 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01430507

Locations
India
Advance Rheumatology Clinic
Hyderabad, Andhra Pradesh, India
Mahavir Hospital and Research Center
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
Shalby Hospitals
Ahmedabad, Gujarat, India
Rathi Orthopaedic & Research Center
Ahmedabad, Gujarat, India
Chanre Rheumatology and Immunology centre and Research
Bangalore, Karnataka, India
M S Ramaiah Medical College and Hospital
Bangalore, Karnataka, India
Kennisha Rheumatology Care & Diagnostics
Mumbai, Maharashtra, India
Sushrut Hospital Research Centre and PG Institute of Orthopaedics
Nagpur, Maharashtra, India
Vidarbha Arthritis & Superspeciality Clinic
Nagpur, Maharashtra, India
Chennai Meenakshi Multispeciality Hospital Limited
Chennai, Tamil Nadu, India
Chhatrapati Shahuji Maharaj Medical University
Lucknow, Uttar Pradesh, India
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Lucknow, Uttar Pradesh, India
Institute of Post Graduate Medical Education & Research (IPGMER)
Kolkata, West Bengal, India, 700020
Philippines
Brokenshire Memorial Hospital
Davao City, Davao, Philippines
University of Perpetual Help Dalta Medical Center
Las Pinas City, Metro Manila, Philippines
Manila Doctors Hospital
Manila, Metro Manila, Philippines
University of Santo Tomas Hospital
Manila, Metro Manila, Philippines
St. Luke's Medical Center
Quezon City, Metro Manila, Philippines
Internal Medicine and Rheumatology, Chong Hua Hospital
Cebu, Philippines
Department of Medicine, Davao Doctor's Hospital
Davao, Philippines
Poland
Oddział Kliniczny Reumatologii i Ukladowych Chorob Tkanki Lacznej
Bydgoszcz, Wojewodztwo kujawsko pomorskie, Poland
NZOZ Reumed
Lublin, Wojewodztwo lubelskie, Poland
Osrodek Badan Klinicznych Prof. Dr hab. med.
Lublin, Wojewodztwo lubelskie, Poland
Niepubliczny Zaklad Opieki Zdrowotnej Medica Pro Familia Sp. z o.o.
Warszawa, Wojewodztwo lubelskie, Poland, 01-868
Centrum Medyczne MEDENS S.C. Grupowa Praktyka Lekarska
Chelm Slaski, Wojewodztwo slaskie, Poland
Specjalistyczna Praktyka Lekarska Joanna Badowska
Czestochowa, Wojewodztwo slaskie, Poland
Wojewodzki Zespol Specjalistycznej Opieki Zdrowotnej
Wroclaw, Wojewodztwo slaskie, Poland, 50-403
Sri Lanka
Teaching Hospital Karapitiya
Galle, Colombo, Sri Lanka
Colombo South Teaching Hospital
Colombo, Sri Lanka
Nawaloka Hospitals PLC
Colombo, Sri Lanka
National Hospital of Sri Lnka
Colombo, Sri Lanka
United Kingdom
Queen's Hospital
Romford, Essex, United Kingdom
The Leeds Teaching Hosptial NHS Trust, Chapel Allerton Hospital
Leeds, Yorkshire, United Kingdom
Sponsors and Collaborators
Glenmark Pharmaceuticals Ltd. India
Glenmark Pharmaceuticals SA
Investigators
Study Director: Dr Lalit Lakhwani Glenmark Pharamceuticals SA
  More Information

No publications provided

Responsible Party: Glenmark Pharmaceuticals Ltd. India
ClinicalTrials.gov Identifier: NCT01430507     History of Changes
Other Study ID Numbers: GRC 4039-203, 2011-000107-40
Study First Received: September 7, 2011
Last Updated: December 27, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Drugs Controller General of India
Philippines: Bureau of Food and Drugs

Keywords provided by Glenmark Pharmaceuticals Ltd. India:
Anti-inflammatory drugs, DMARD

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 23, 2014