A Study Evaluating the Efficacy and Safety of CKD-506 in Adult Subjects With Moderate-to-Severe Rheumatoid Arthritis and Inadequate Response to Methotrexate

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the effects of CKD-506 on signs and symptoms of RA in subjects with moderate-to-severe RA who are inadequate responders to methotrexate.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2a Study Investigating the Efficacy, Safety, Pharmacokinetic and Biomarker Profiles of CKD-506 Administered to Adult Subjects With Moderate-to- Severe Rheumatoid Arthritis and Inadequate Response to Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: CKD-506
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of RA for at least 6 months prior to Screening, currently meet the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for RA, and are ACR functional class I-III. Have active RA Ongoing treatment with a stable dose of MTX as described below: Use of oral or injectable MTX on a continuous basis for at least 12 weeks prior to Baseline and on a stable dose and route of administration between 15 mg and 25 mg/weekly for at least 8 weeks prior to Baseline and planned during the study. Subjects should be on an adequate and stable dose of folic acid for at least 4 weeks prior to first administration of study treatment and planned during the study. Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for at least 12 weeks after the last dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test at Screening and urine pregnancy test at Baseline Sexually active men, if not surgically sterile, must agree to use a medically acceptable form of contraception during the study and continue its use for at least 12 weeks after the last dose of study treatment. Exclusion Criteria: Treatments for RA as follows: JAK inhibitors at any time; use of any currently licensed biologics with DMARD properties at any time. Use of oral steroids at a dose >10 mg/day of prednisone or prednisone equivalent or at a dose that has not been stable for at least 4 weeks prior to Screening. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) which have not been at a stable dose or route of administration for at least 2 weeks prior to Baseline and planned during the study. History of tuberculosis (TB) infection. Positive serology for human immunodeficiency virus 1 or 2, hepatitis B virus or hepatitis C virus. Currently active infection or history of infection within the last 2 weeks of Screening or Baseline

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Tablets for oral administration<br>|
| Experimental: CKD-506 Dose A<br> | Drug: CKD-506<br>* Tablets for oral administration<br>|
| Experimental: CKD-506 Dose B<br> | Drug: CKD-506<br>* Tablets for oral administration<br>|
| Experimental: CKD-506 Dose C<br> | Drug: CKD-506<br>* Tablets for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in DAS28(CRP) at week 12 |  | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to treatment based on the American College of Rheumatology 20% response criteria (ACR20) at Weeks 2, 4, 8, and 12 |  | At weeks 2, 4, 8 and 12 | 
| Change from Baseline in DAS28(CRP) at Weeks 2, 4, and 8 |  | Baseline and up to week 8 | 
| Response to treatment based on the ACR50 criteria at Weeks 2, 4, 8, and 12 |  | At weeks 2, 4, 8 and 12 | 
| Response to treatment based on the ACR70 criteria at Weeks 2, 4, 8, and 12 |  | At weeks 2, 4, 8 and 12 | 
| Change from Baseline in ACRn at Weeks 2, 4, 8, and 12 |  | Baseline and up to week 12 | 
| Change from Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) at Weeks 4 and 12 |  | Baseline and weeks 4, 12 | 
| Change from Baseline in the duration of morning stiffness (in minutes and in severity as measured with a visual analog scale [VAS]) at Weeks 2, 4, 8, and 12 | Morning stiffness severity was determined by the Patient's Assessment of Severity and Duration of Morning Stiffness questionnaire. Participants rated the severity of morning stiffness on awakening over the past 7 days on a scale from 0 (No morning stiffness) to 10 (Worst possible morning stiffness). | Baseline and up to week 12 | 
| Change from Baseline in the Short Form-36 item Health Survey (SF-36) at Weeks 4 and 12 | The Short Form-36 item Health Survey (SF-36) consists of eight scaled scores; physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. which are the weighted sums of the questions in their section. Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state. | Baseline and weeks 4, 12 | 
| Change from Baseline in the Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, and 12 |  | Baseline and up to week 12 | 
| Change from Baseline in the Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, and 12 |  | Baseline and up to week 12 | 
| Response to treatment based on the achievement of Low Disease Activity (LDA) status based on each of the following definitions at Weeks 2, 4, 8,and 12: DAS28(CRP) ≤ 3.2, SDAI ≤ 11.0, CDAI ≤ 10.0 at Weeks 2, 4, 8, and 12 |  | At weeks 2, 4, 8 and 12 | 
| Response to treatment based on the achievement of remission based on each of the following definitions at Weeks 2, 4, 8, and 12: DAS28(CRP) < 2.6, Boolean parameters, SDAI ≤ 3.3, CDAI ≤ 2.8 at Weeks 2, 4, 8, and 12 |  | At weeks 2, 4, 8 and 12 | 
| Improvement of physical ability defined as change from Baseline in HAQ-DI ≥ 0.22 at Weeks 2, 4, 8, and 12 |  | Baseline and up to week 12 |