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

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Revamilast; Drug: Revamilast; Drug: Revamilast; Drug: Placebo Comparator

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Medium Dose; Medium Dose Revamilast	Drug: Revamilast; Tablet, Low dose, Once daily for 12 weeks; Drug: Revamilast; Tablet, Medium dose, Once daily for 12 weeks; Drug: Revamilast; Tablet, High dose, Once daily for 12 weeks
EXPERIMENTAL: High Dose; High Dose Revamilast	Drug: Revamilast; Tablet, Low dose, Once daily for 12 weeks; Drug: Revamilast; Tablet, Medium dose, Once daily for 12 weeks; 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; Drug: Revamilast; Tablet, Medium dose, Once daily for 12 weeks; Drug: Revamilast; Tablet, High dose, Once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients achieving ACR20 response	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients achieving ACR50 and ACR 70 response	12 weeks
Change in DAS-28 score	week 12
Change in serum CRP and ESR values	12 weeks
Frequency and use of rescue medication	12 weeks

Collaborators and Investigators

• Sponsor: Glenmark Pharmaceuticals Ltd. India
• Collaborators: Glenmark Pharmaceuticals S.A.
• Investigators: Study Director: Dr Lalit Lakhwani, Glenmark Pharamceuticals SA

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): December 1, 2012
• Study Completion (ACTUAL): December 1, 2012

Study Registration Dates

• First Submitted: September 7, 2011
• First Submitted That Met QC Criteria: September 7, 2011
• First Posted (ESTIMATE): September 8, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): December 28, 2012
• Last Update Submitted That Met QC Criteria: December 27, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Anti-inflammatory drugs, DMARD
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: GRC 4039-203; 2011-000107-40 (EUDRACT_NUMBER)