Clinical trial NCT01430507: A Clinical Trial to Study the Effects of Revamilast in Patients With Rheumatoid Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Anti-inflammatory drugs, DMARD
Lead sponsor: Glenmark Pharmaceuticals Ltd. India
Sponsor class: INDUSTRY
Collaborators: name: Glenmark Pharmaceuticals S.A.
First posted: 2011-09-08
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of patients achieving ACR20 response
timeFrame: 12 weeks
Secondary outcomes:
measure: Percentage of patients achieving ACR50 and ACR 70 response
timeFrame: 12 weeks
measure: Change in DAS-28 score
timeFrame: week 12
measure: Change in serum CRP and ESR values
timeFrame: 12 weeks
measure: Frequency and use of rescue medication
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: Advance Rheumatology Clinic
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Mahavir Hospital and Research Center
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Sri Deepti Rheumatology Center
state: Andhra Pradesh
city: Secunderabad
country: India
facility: Krishna Institute of Medical Sciences
state: Andhra Pradesh
city: Vadodara
country: India
facility: Centre for Knee & Hip Surgery
state: Gujarat.
city: Ahmedabad
country: India
facility: Rathi Orthopaedic & Research Center
state: Gujarat
city: Ahmedabad
country: India
facility: Shalby Hospitals
state: Gujarat
city: Bangalore
country: India
facility: Chanre Rheumatology and Immunology centre and Research
state: Karnataka
city: Bangalore
country: India
facility: M S Ramaiah Medical College and Hospital
state: Karnataka
city: Mumbai
country: India
facility: Kennisha Rheumatology Care & Diagnostics
state: Maharashtra
city: Nagpur
country: India
facility: Sushrut Hospital Research Centre and PG Institute of Orthopaedics
state: Maharashtra
city: Nagpur
country: India
facility: Vidarbha Arthritis & Superspeciality Clinic
state: Maharashtra
city: Chennai
country: India
facility: Chennai Meenakshi Multispeciality Hospital Limited
state: Tamil Nadu
city: Lucknow
country: India
facility: Chhatrapati Shahuji Maharaj Medical University
state: Uttar Pradesh
city: Lucknow
country: India
facility: Sanjay Gandhi Postgraduate Institute of Medical Sciences
state: Uttar Pradesh
city: Kolkata
country: India
facility: Institute of Post Graduate Medical Education & Research (IPGMER)
state: West Bengal
city: Davao City
country: Philippines
facility: Brokenshire Memorial Hospital
state: Davao
city: Las Pinas City
country: Philippines
facility: University of Perpetual Help Dalta Medical Center
state: Metro Manila
city: Manila
country: Philippines
facility: Manila Doctors Hospital
state: Metro Manila
city: Manila
country: Philippines
facility: University of Santo Tomas Hospital
state: Metro Manila
city: Quezon City
country: Philippines
facility: St. Luke's Medical Center
state: Metro Manila
city: Cebu
country: Philippines
facility: Internal Medicine and Rheumatology, Chong Hua Hospital
city: Davao
country: Philippines
facility: Department of Medicine, Davao Doctor's Hospital
city: Bydgoszcz
country: Poland
facility: Oddział Kliniczny Reumatologii i Ukladowych Chorob Tkanki Lacznej
state: Wojewodztwo kujawsko pomorskie
city: Lublin
country: Poland
facility: NZOZ Reumed
state: Wojewodztwo lubelskie
city: Lublin
country: Poland
facility: Osrodek Badan Klinicznych Prof. Dr hab. med.
state: Wojewodztwo lubelskie
city: Warszawa
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Medica Pro Familia Sp. z o.o.
state: Wojewodztwo lubelskie
city: Chelm Slaski
country: Poland
facility: Centrum Medyczne MEDENS S.C. Grupowa Praktyka Lekarska
state: Wojewodztwo slaskie
city: Czestochowa
country: Poland
facility: Specjalistyczna Praktyka Lekarska Joanna Badowska
state: Wojewodztwo slaskie
city: Wroclaw
country: Poland
facility: Wojewodzki Zespol Specjalistycznej Opieki Zdrowotnej
state: Wojewodztwo slaskie
city: Galle
country: Sri Lanka
facility: Teaching Hospital Karapitiya
state: Colombo
city: Colombo
country: Sri Lanka
facility: Colombo South Teaching Hospital
city: Colombo
country: Sri Lanka
facility: National Hospital of Sri Lnka
city: Colombo
country: Sri Lanka
facility: Nawaloka Hospitals PLC
city: Romford
country: United Kingdom
facility: Queen's Hospital
state: Essex
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hosptial NHS Trust, Chapel Allerton Hospital
state: Yorkshire
Study officials:
affiliation: Glenmark Pharamceuticals SA
name: Dr Lalit Lakhwani
role: STUDY_DIRECTOR
References: