A Safety & Efficacy Study of Treatment With AP1189 in Rheumatoid Arthritis Patients naïve to DMARD Treatment

Study Overview
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Brief Summary
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The study is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of 12 weeks daily treatment with 100 mg AP1189 in RA patients who are to start up-titration with methotrexate (MTX).

Official Title
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A Double-blind, Multi-center, Randomized, Placebo-controlled Study of the Safety and Efficacy of 12 Weeks Extended Treatment With AP1189 in Early Rheumatoid Arthritis (RA) Patients naïve to DMARD Treatment

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: 100 mg AP1189
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Confirmed diagnosis of RA according to the 2010 ACR/EULAR RA classification criteria and are ACR class I-III ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts). Candidate for MTX treatment Is about to begin treatment with MTX Must meet at least one of the following parameters at Screening: positive result for anti-CCP or RF Serum CRP ≥ 6 mg/L Highly active RA (CDAI > 22) at screening and baseline Negative QuantiFERON-in-Tube test (QFG-IT) Females of child-bearing potential must use of highly effective birth control method Main Exclusion Criteria: Major surgery (including joint operation) within 8 weeks prior to screening or planned surgery within 1 month following randomization Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or significant systemic involvement secondary to RA. Sjögren's syndrome with RA is allowable Prior history of or current inflammatory joint disease other than RA Subjects with fibromyalgia Use of hydroxychloroquine within 4 weeks prior the Screening Visit Initiation of, or change in existing NSAID treatment within 2 weeks prior to the baseline visit Corticosteroids except inhaled or nasal formulations for seasonal allergy or asthma are prohibited within 2 weeks prior to screening Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disease Have prior renal transplant, current renal dialysis, or severe renal insufficiency Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids Evidence of active malignant disease (except basal cell carcinoma of the skin that has been excised and cured) Neuropathies or other painful conditions that might interfere with pain evaluation Body weight of >150 kg HBsAg positive and/or Anti-HBc with sign of current infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Interventional Model Description: Multi-center, randomized, double-blind, placebo-controlled study with 12 weeks of treatment with AP1189 or placebo
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100 mg AP1189<br>Treatment period of 12 weeks given as 1 tablet daily | Drug: 100 mg AP1189<br>* AP1189 tablets for oral use<br>* Other names: AP1189 tablets for oral use;|
| Placebo Comparator: Placebo<br>Treatment period of 12 weeks given as 1 tablet daily | Drug: Placebo<br>* Matching placebo for oral use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of reported AEs | Evaluation of the safety and tolerability of AP1189 on the number and severity of reported Adverse Events, compared with placebo | 12 weeks | 
| Change in ACR20 | The change in American College of Rheumatology 20% (ACR20) compared to baseline | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ACR50 | The change in American College of Rheumatology 50% (ACR50) compared to baseline | 12 weeks | 
| Change in ACR70 | The change in American College of Rheumatology 70% (ACR70) compared to baseline | 12 weeks | 
| Change in (CDAI) | The change Clinical Disease Activity Index (CDAI) compared to baseline | 12 weeks | 
| Change in DAS-28 | The change in DAS-28, based on a CRP value, compare to baseline | 12 weeks |