Study of Iguratimod Plus Methotrexate Compared to Leflunomid Plus Methotrexate in Patients With Rheumatoid Arthritis

A Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Iguratimod or Leflunomide in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis

This study is intended to evaluate the efficacy and safety of Iguratimod Plus Methotrexate Compared to Leflunomid Plus Methotrexate in patients with active Rheumatoid Arthritis (RA).

Study Overview

• Status: Unknown
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Iguratimod; Drug: Methotrexate; Drug: Leflunomide

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: weihong zhao, doctor; Phone Number: 8701 +86(25) 8556 6666; Email: zhaoweihong@simcere.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100032
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Fengchun Zhang, doctor; Phone Number: +86（10）6915 6114; Email: zhangfccra@yahoo.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with a diagnosis of RA according to the diagnostic criteria of the American College of Rheumatology (ACR) (revised in 1987)
• Rheumatoid Arthritis for more than 3 months from the time of the initial diagnosis
• Functional Class II-III
• Subjects have active RA at the time of screening
• Subjects with inadequate response to biologics should have a washout period before the initiation of study. For etanercept, washout period should be 2-week, and 8-week for infliximab and adalimumab.
• For firstly diagnostic RA patients, the disease activity should be moderate to severe, with DAS28>3.2
• Must have at least 4 tender joints (66 join count) and 8 swollen joints( 68 join count) at screening and baseline
• Has a C-reactive protein ≥ 10 mg/L(or 1.0 mg/dL) OR Erythrocyte Sedimentation Rate (ESR) ≥ 28 mm/hr
• Must have a negative Pregnancy test and use adequate method of contraception throughout the trial
• Written informed consent

Exclusion Criteria:

• Preceding treatment with DMARDs, immunosuppressants (cyclophosphamide, cyclosporine, azathioprine, etc.), or Tripterygium within 4 weeks prior to study entry
• Subjects have been treated with iguratimod or leflunomide combined with MTX before screening.
• Subjects combined with other autoimmune disease, such as systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleriasis and polymyositis, except for Sjögren syndrome.
• Chest x-ray abnormalities, such as tuberculosis, interstitial pulmonary fibrosis, etc.
• ALT >1.5×ULN, AST >1.5×ULN, Cr >135umol/L, total bilirubin>1.5×ULN
• WBC<4×109/L，HGB<85g/L，PLT<100×109/L
• Subjects with serious cardiovascular, renal, hematologic, endocrine diseases or malignant
• Women of Pregnant or breastfeeding, and male or female with recent plan to conception
• Subjects with immunodeficiency, uncontrolled infection and active gastrointestinal disease
• Allergic to any of the study drugs
• History of alcoholism
• Subjects with mental illness
• Subjects receiving live vaccines recently
• Subjects participating in other clinical study within 3 months prior to study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iguratimod and MTX combination; Drug:Iguratimod 25 mg/tablet, taken orally, 2 tablets/day (bid) Drug:MTX 2.5 mg/tablet, taken orally once a week, 4 tablets/week	Drug: Iguratimod; Iguratimod 25 mg/tablet, taken orally, 2 tablets/day (bid),52 weeks; Other Names: Iremod; Drug: Methotrexate; Methotrexate 2.5 mg/tablet, taken orally once a week, 4 tablets/week,52 weeks
Active Comparator: Leflunomide and MTX combination; Drug: Leflunomide 10 mg/tablet, taken orally, 2 tablets/day (bid) Drug: Methotrexate 2.5 mg/tablet, taken orally once a week, 4 tablets/week	Drug: Methotrexate; Methotrexate 2.5 mg/tablet, taken orally once a week, 4 tablets/week,52 weeks; Drug: Leflunomide; Leflunomide 10 mg/tablet, taken orally, 2 tablets/day (bid),52 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients with ACR 20 response and Change in Disease Activity as measured by the DAS28	week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in modified Total Sharp Score (mTSS)	week 52
Percentage of patients with ACR 50 response and ACR70 response	week 24,week 52
Change from baseline in number of swollen and tender joins, Erythrocyte sedimentation rate (ESR) ,C-reactive protein (CRP),anti-citrullinated-protein antibody (ACPA) and heumatoid factor(RF)	week 24, week 52
Time to achieve the ACR20, ACR50 and ACR70	week 12, week 24, week 40, week 52
Percentage of patients with Simplified Disease Activity Index (SDAI) ≤ 3.3 and change from baseline in Health Assessment Questionnaire (HAQ)	week 12, week 24, week 40, week 52
Incidence of adverse events	up to 52 weeks

Collaborators and Investigators

• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): February 1, 2016

Study Registration Dates

• First Submitted: October 23, 2014
• First Submitted That Met QC Criteria: October 23, 2014
• First Posted (Estimate): October 27, 2014

Study Record Updates

• Last Update Posted (Estimate): October 27, 2014
• Last Update Submitted That Met QC Criteria: October 23, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Leflunomide
• Other Study ID Numbers: Tranmod