Efficacy and Safety of Iguratimod in Patients With Hand Osteoarthritis (ESIGO)

Study Overview
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Brief Summary
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Hand osteoarthritis is one of the most common arthritis, resulting in pain in finger and thumb base joints. The disease is characterized by pain and stiffness of the affected joints and is the most common cause of disability in aged people. Currently limited therapy options are available. Synovial inflammation is involved in the joint pain. Iguratimod is a small disease-modifying compound that can influence anti-inflammatory pathways in models of rheumatoid arthritis. It has an anabolic effect on the bone metabolism of infected joint by osteoclastogenesis inhibition and osteoblast differentiation. The investigators hypothesize that Iguratimod will alleviate pain of patient with inflammatory hand osteoarthritis, and that a beneficial effect of Iguratimod on pain will be accompanied by a decrease of synovial inflammation.

Official Title
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Efficacy and Safety of Iguratimod in Patients With Hand Osteoarthritis (ESIGO) : a Randomized Control Trial

Conditions
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Hand Osteoarthritis, Inflammatory Arthritis

Intervention / Treatment
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* Drug: Iguratimod
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Patients to be included must meet the following criteria: Age of 45-75 years. Men or women. Hand OA according to the ACR criteria. Symptomatic interphalangeal osteoarthritis for more than 3 months (at least every other day). At least 1 IPJ (DIP/PIP/IP1st) with soft tissue swelling or erythema. At least 1 IPJ with positive power Doppler signal or/and synovial thickening of at least grade 2 on ultrasound. Finger pain which was more than 40 mm as evaluated by visual analogue scales (VAS) (0-100 mm) in the preceding 48 hours. Be able to adhere to the study visit schedule and other protocol requirements. Capable of giving informed consent and the consent must be obtained prior to any screening procedures. Exclusion Criteria: Other known medical disease that may affect joints, e.g. rheumatoid arthritis, gout, psoriatic arthritis, reactive arthritis, ankylosing spondylitis, Lyme disease, Systemic lupus erythematosus, Sjogren Syndrome, Systemic sclerosis. Psoriasis. involving carpometacarpal [CMC] joints, without interphalangeal joints. Existence of painful syndrome of upper limbs likely to interfere with the monitoring of pain (cervicobrachial neuralgia, incapacitating carpal tunnel syndrome, joint disorders of the elbow or shoulder, poly-articular chondrocalcinosis, fibromyalgia). Trigger finger, injury in joints within past 6 months. Slow-acting drugs for OA (e.g. glucosamine, chondroitin, diacerhein) initiated within the previous 3 months before the study. Intra-articular treatments or aspirations of any kind of any joint in the hands 3 months before screening. Intra-articular corticosteroids into any joint or use of systemic corticosteroids 1 month before screening. Treatment with analgesics initiated within the previous 1 month and NSAIDs initiated within the previous 2 weeks. History of hand surgery within 12 months prior enrolment. Participation in experimental device or experimental drug study 3 months prior to enrolment. Scheduled surgery during study participation. Pregnant or lactating women，planned pregnancy within the study period, 3 months after end of study treatment for female fertile participant. Known blood dyscrasias and coagulation disorders. Elevated alanine transaminase (AST/ALT > 2x upper normal range). GRF (MDRD) < 60 mg/min/1.73m2. Known viral hepatitis B or C. Uncontrolled diseases, such as asthma or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids. History of peptic ulcer. Patients who have severe comorbidities, including cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, GI disease. Known any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or which obstruct participation, such as e.g. psychiatric disorders.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Iguratimod group<br>subjects with Iguratimod | Drug: Iguratimod<br>* iguratimod, 25mg bid po.<br>|
| Placebo Comparator: placebo group<br>subjects with placebo | Drug: placebo<br>* placebo 1 tablet bid po.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in patient's assessment of arthritis pain on a visual analogue scale | Change from baseline in self-reported finger joint pain previous 48 hours on a 0-100 mm scale at 12 weeks of treatment; higher value indicate worse outcome. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in patient's assessment of arthritis pain on a visual analogue scale prior to each visit | Differences in self-reported finger joint pain previous 48 hours on a 0-100 mm scale at 4 weeks, 8 weeks, and 12 weeks; higher value indicate worse outcome. | 4 weeks, 8 weeks, 12 weeks | 
| Change from baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) scores at each visit. | The AUSCAN Index is a self-administered questionnaire consisting of a 15-item scale which measures pain (5 items), stiffness (1 item) and degree of disability/physical function (9 items) during the preceding 48 hours; higher value indicate worse outcome. | 4 weeks, 8 weeks, 12 weeks | 
| Change from baseline in Functional Index for Hand Osteoarthritis (FIHOA) | The Functional Index for Hand Osteoarthritis (FIHOA) is a leading assessment tool for hand OA-related functional impairment; higher value indicate worse outcome. | 12 weeks | 
| Change from baseline in Health Assessment Questionnaire Disability Index (HAQ) | Change from baseline in Health Assessment Questionnaire Disability Index (HAQ) at week 12; higher value indicate worse outcome. | 12 weeks | 
| Change from baseline in the Scores of SF-36 questionnaire | Change from baseline in SF-36, including physical and mental component sores (PCS and MCS) at week 12; higher value indicate worse outcome. | 12 weeks | 
| Change from baseline in Michigan Hand Outcomes Questionnaire (MHOQ) | Michigan Hand Outcomes Questionnaire (MHOQ) pain and physical function subscales; function subscale range 10-50, higher value indicate worse outcome; task subscale range 17-85, higher value indicate worse outcome; work subscale range 5-25, higher value indicate worse outcome; pain subscale range 10-48, higher value indicate better outcome. | 12 weeks | 
| Change from baseline in Ultrasound record | Ultrasound record: number of finger joints with synovial thickening and power Doppler signals. | 12 weeks | 
| Change from baseline in OMERACT hand OA magnetic resonance imaging score | OMERACT hand OA magnetic resonance imaging score includes synovitis (0-3), erosive damage(0-3), cyst (0-3), osteophyte (0-3), cartilage space loss(0-3), malalignment (0-3), and bone marrow lesions (0-3); higher value indicate worse outcome | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inflammatory hand osteoarthritis, iguratimod, a randomized control trial