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

Rheumatoid Arthritis Clinical Trial

— TERRA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01430507
• Other study ID #: GRC 4039-203
• Secondary ID: 2011-000107-40
• Status: Completed
• Phase: Phase 2
• First received: September 7, 2011
• Last updated: December 27, 2012
• Start date: September 2011
• Est. completion date: December 2012

Study information

• Verified date: August 2012
• Source: Glenmark Pharmaceuticals Ltd. India
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyIndia: Drugs Controller General of IndiaPhilippines: Bureau of Food and Drugs
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 406
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Revamilast
Tablet, Low dose, Once daily for 12 weeks
• Revamilast
Tablet, Medium dose, Once daily for 12 weeks
• Revamilast
Tablet, High dose, Once daily for 12 weeks
• Placebo Comparator
Matching Placebo in triple dummy format, Tablet, Once daily for 12 weeks

Locations

Country	Name	City	State
India	Rathi Orthopaedic & Research Center	Ahmedabad	Gujarat
India	Shalby Hospitals	Ahmedabad	Gujarat
India	Chanre Rheumatology and Immunology centre and Research	Bangalore	Karnataka
India	M S Ramaiah Medical College and Hospital	Bangalore	Karnataka
India	Chennai Meenakshi Multispeciality Hospital Limited	Chennai	Tamil Nadu
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	Institute of Post Graduate Medical Education & Research (IPGMER)	Kolkata	West Bengal
India	Chhatrapati Shahuji Maharaj Medical University	Lucknow	Uttar Pradesh
India	Sanjay Gandhi Postgraduate Institute of Medical Sciences	Lucknow	Uttar Pradesh
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	Krishna Institute of Medical Sciences	Secunderabad	Andhra Pradesh
India	Centre for Knee & Hip Surgery	Vadodara	Gujarat.
Philippines	Internal Medicine and Rheumatology, Chong Hua Hospital	Cebu
Philippines	Department of Medicine, Davao Doctor's Hospital	Davao
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
Poland	Oddzial Kliniczny Reumatologii i Ukladowych Chorob Tkanki Lacznej	Bydgoszcz	Wojewodztwo kujawsko pomorskie
Poland	Centrum Medyczne MEDENS S.C. Grupowa Praktyka Lekarska	Chelm Slaski	Wojewodztwo slaskie
Poland	Specjalistyczna Praktyka Lekarska Joanna Badowska	Czestochowa	Wojewodztwo slaskie
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	Wojewodzki Zespol Specjalistycznej Opieki Zdrowotnej	Wroclaw	Wojewodztwo slaskie
Sri Lanka	Colombo South Teaching Hospital	Colombo
Sri Lanka	National Hospital of Sri Lnka	Colombo
Sri Lanka	Nawaloka Hospitals PLC	Colombo
Sri Lanka	Teaching Hospital Karapitiya	Galle	Colombo
United Kingdom	The Leeds Teaching Hosptial NHS Trust, Chapel Allerton Hospital	Leeds	Yorkshire
United Kingdom	Queen's Hospital	Romford	Essex

Sponsors (2)

Lead Sponsor	Collaborator
Glenmark Pharmaceuticals Ltd. India	Glenmark Pharmaceuticals S.A.

Countries where clinical trial is conducted

India,  Philippines,  Poland,  Sri Lanka,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients achieving ACR20 response		12 weeks	No
Secondary	Percentage of patients achieving ACR50 and ACR 70 response		12 weeks	No
Secondary	Change in DAS-28 score		week 12	No
Secondary	Change in serum CRP and ESR values		12 weeks	No
Secondary	Frequency and use of rescue medication		12 weeks	Yes