A Study to Evaluate the Effectiveness and Safety of SKI-O-703 in Patients Experiencing Active Rheumatoid Arthritis Despite Treatment With Conventional Therapies.

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of SKI-O-703 compared with placebo, in patients with active rheumatoid arthritis (RA) who have had an inadequate response to conventional synthetic disease-modifying agents. Patients will be randomly assigned to one of 4 groups and will receive one of three doses of SKI-O-703 or placebo, administered orally twice daily for 12 weeks.

Official Title
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A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study to Evaluate the Efficacy and Safety of Oral SKI-O-703 in Patients With Active Rheumatoid Arthritis Despite Treatment With Conventional Therapies

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: SKI-O-703
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must provide written, signed, informed consent. Patients must have a diagnosis of Rheumatoid Arthritis (RA) according to American College of Rheumatology (ACR) criteria or the 2010 ACR/European League Against Rheumatism classification, for at least 6 months prior to first administration of study drug. Patients must have active RA at screening and baseline (Day 1 of the study). Patients who have active disease despite csDMARD (conventional synthetic disease-modifying antirheumatic drugs) therapy for at least 3 months prior to Day 1 of the study. Patients must have had an inadequate response to previous anti-TNF⍺ (anti-tumor necrosis factor alpha) biological agent(s) for the treatment of RA and meet the washout period prior to Day 1 of the study. Exclusion Criteria: Patients receiving oral agents, except for medications listed in inclusion criteria for the treatment of RA. Patients who have previously received any other or biological agent for the treatment of RA, other than anti-TNF⍺ inhibitor(s). Patients who have a current or past history of hepatitis B virus (HBV) infection; positive test for hepatitis C virus (HCV) antibody; positive test for human immunodeficiency virus (HIV); history of or concurrent interstitial pneumonia; acute infection requiring oral antibiotics within 2 weeks, or parenteral injection of antibiotics within 4 weeks prior to first administration of the study drug; other serious infection within 6 months prior to first administration of study drug; recurrent herpes zoster or other chronic or recurrent infection within 6 weeks prior to first administration of the study drug; past or current granulomatous infections or other severe or chronic infection; positive test for tuberculosis (TB) or other evidence of TB. Patients with uncontrolled diabetes mellitus, or uncontrolled hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg). Patients with any other inflammatory or rheumatic diseases that could impact the evaluation of the effect of the study drug. Patients with a history of malignancy within 5 years prior to first administration of the study drug, except completely excised and cured squamous cell carcinoma, carcinoma of the cervix in situ, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma. New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled cardiac disease or heart attack within 6 months prior to first administration of the study drug. Female patients who are currently pregnant, breastfeeding or planning to become pregnant or breastfeed within 6 months of the last dose of the study drug. Other protocol-defined inclusion/exclusion criteria could apply.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SKI-O-703 100 mg<br> | Drug: SKI-O-703<br>* Oral administration, twice per day<br>|
| Experimental: SKI-O-703 200 mg<br> | Drug: SKI-O-703<br>* Oral administration, twice per day<br>|
| Experimental: SKI-O-703 400 mg<br> | Drug: SKI-O-703<br>* Oral administration, twice per day<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Oral administration, twice per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in disease activity score | Mean change from baseline in disease activity score for 28 joints (DAS28) using hsCRP (high sensitivity C-reactive protein) | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Percentage of patients with ACR20 (American College of Rheumatology 20) score | ACR20 score is the percentage of patients showing ≥20% improvement from baseline in tender joint count (68 joint counts), ≥20% improvement in swollen joint count (66 joint counts), and ≥20% improvement in at least 3 of the following: patient's global assessment of arthritis pain; patient's global assessment of disease activity; physician's global assessment of disease activity; health assessment questionnaire-disability index (HAQ-DI); hsCRP (high sensitivity C-reactive protein) | Baseline and Weeks 2, 4 8 and 12 | 
| • Percentage of patients with ACR50 (American College of Rheumatology 50) score | ACR50 score is the percentage of patients showing ≥50% improvement from baseline in tender joint count (68 joint counts), ≥50% improvement in swollen joint count (66 joint counts), and ≥50% improvement in at least 3 of the following: patient's global assessment of arthritis pain; patient's global assessment of disease activity; physician's global assessment of disease activity; health assessment questionnaire-disability index (HAQ-DI); hsCRP (high sensitivity C-reactive protein) | Baseline and Weeks 2, 4 8 and 12 | 
| • Percentage of patients with ACR70 (American College of Rheumatology 70) score | ACR70 score is the percentage of patients showing ≥70% improvement from baseline in tender joint count (68 joint counts), ≥70% improvement in swollen joint count (66 joint counts), and ≥70% improvement in at least 3 of the following: patient's global assessment of arthritis pain; patient's global assessment of disease activity; physician's global assessment of disease activity; health assessment questionnaire-disability index (HAQ-DI); hsCRP (high sensitivity C-reactive protein) | Baseline and Weeks 2, 4 8 and 12 | 
| Health Assessment Questionnaire-Disability Index (HAQ-DI) score | Change from baseline measured by disability index | Baseline and Weeks 2, 4 8 and 12 | 
| Incidence of Adverse Events (AEs) |  | Up to Week 16 | 
| Incidence of Serious Adverse Events (SAEs) |  | Up to Week 16 |