Rheumatoid Arthritis Despite Treatment With Conventional Therapies MedDRA version: 21.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Oscotec Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject is an adult male or female aged =18 years old at time of signing the informed consent (or per local customs for =19 years of age for Korean subjects). 2. Subject with Body Mass Index (BMI) of =18 and <40 kg/m2 at screening. 3. Subject who has a diagnosis of RA according to the 1987 ACR criteria (Appendix 13.2) or the 2010 ACR/EULAR classification criteria (Appendix 13.3) for at least 6 months prior to Day 1. 4. Subject has active disease at screening and baseline following treatment of RA with inadequate response to csDMARDs or anti-TNFa biological agent(s) as per 2012 update of the 2008 ACR RA treatment recommendations. a. Active disease is defined as: - presence of =5 swollen joints and - serum hsCRP concentration =0.6 mg/dL b. At least ONE of the following treatments for RA must have been received: - anti-TNFa biological agent(s): Includes at least 1 of the following treatments, with completed washout period indicated prior to Day 1 dosing - csDMARD therapy: Includes at least 1 of the following dosing regimen for at least 90 days of continuous use (prior to Day 1 dosing)*o MTX 15 to 25 mg/week. If the current MTX dose is <15 mg/week, the subject's intolerance to =7.5 mg dose must be documented in the subject's medical history *Note: Combinations of up to 2 csDMARDs are allowed. However, combination of MTX and leflunomide is not allowed. Subjects are allowed to continue taking csDMARD therapy at stable doses (initiated =4 weeks prior to the first dose of study drug) throughout the study period. a) If subjects have to discontinue csDMARD therapy (except for leflunomide), the washout windows 30 days prior to Day 1 dosing must be observed b) If subjects have to discontinue leflunomide due to combination use with MTX before enrollment, the following washout windows must be observed: subjects who discontinued leflunomide and have had successful chelation with 8 g of cholestyramine (3 times daily) for 3 days must wait for 4 weeks prior Day 1 dosing. Subjects who discontinued leflunomide and did not have cholestyramine washout must wait 12 weeks after last dose of leflunomide prior to Day 1 dosing. 5. Subject taking MTX while on study must be willing to take dietary supplement of oral folic acid (or equivalent, such as folinic acid) at a stable dose. 6. Subject who has adequate renal and hepatic function at screening as defined by the following clinical chemistry results: a. Serum creatinine <1.5 × ULN or an estimated creatinine clearance level =50 mL/min (by MDRD GFR equation) b. Serum alanine aminotransferase <2.5 × ULN c. Serum aspartate aminotransferase <2.5 × ULN d. Serum total bilirubin <2 × ULN Repeat of clinical chemistry laboratory tests may be allowed once during screening period (after an approval from medical monitor), if the initial result is unexpected/unexplained (not due to a known underlying condition or concomitant medications or other known cause). 7. Subject who has the following hematology laboratory test results at screening: 8. Subject who can comprehend the full nature and purpose of the study, including possible risks and side effects, to cooperate with the Investigator, to understand verbal and/or written instructions, and to comply with the requirements of the entire study. 9. Subject is informed of the full nature and purpose of the study, including possible risks and side effects, and given ample time and opportunity to read or understand this information, signed and dated the written informed consen
Exclusion criteria
Exclusion criteria: 1. Subject is receiving or has previously received any treatment for RA other than the medications listed in the inclusion criteria for the treatment of RA. 2. Live or live attenuated vaccine within 4 weeks prior to Day 1 dosing or expected need for live vaccination during study participation including at least 4 weeks after the last dose of study drug. 3. Subject has had treatment with any other investigational device or medical product within 4 weeks or 5 half-lives prior to Day 1 dosing, whichever is longer. 4. Subject who (based on the Investigator’s clinical assessment, makes the subject an unsuitable candidate for the study) has any active or recurrent or history of any of the following infections: a. Hepatitis B virus (HBV): Serologic evidence of current/previous HBV infection based on the results of testing for hepatitis B surface antigen (HBsAg) and anti-hepatitis B core (anti-HBc) antibody as follows within 6 weeks of Day 1: b. Hepatitis C virus (HCV): Positive test for antibody confirmed on a subsequent blood sample by RNA-polymerase chain reaction (PCR) assay within 6 weeks of Day 1. c. Human immunodeficiency virus (HIV) 1 or 2: Positive test at screening. d. Mycobacterium tuberculosis (TB): - For subjects with a history of TB, they may be enrolled if the conditions specified in the protocol met - For subjects with an indeterminate result for interferon-gamma release assay (IGRA) or latent TB (defined as a positive result of IGRA with a negative examination of chest x-ray) at Screening, the conditions specified in the protocol met e. Interstitial pneumonia that is judged by the Investigator/subinvestigator to be inappropriate for the subject to participate in this study. f. Granulomatous infections or other severe or chronic infection (such as sepsis, abscess or opportunistic infections, or invasive fungal infection such as histoplasmosis). A subject who has a past diagnosis with sufficient documentation of complete resolution >6 months prior to Day 1 can be enrolled. g. Chronic or recurrent infection (including herpes zoster) within 6 weeks prior to Day 1. h. Acute infection requiring oral antibiotics within 2 weeks or parenteral injection of antibiotics within 4 weeks prior to Day 1. i. Other serious infection as assessed by the Investigator within 6 months prior to Day 1. 5. Subject who has any condition that could confound the evaluation of the data or the effect of the study drug, such as: a. Any other inflammatory or rheumatic diseases, including but not limited to psoriatic arthritis, ankylosing spondylitis, spondyloarthritis, systemic lupus erythematosus, Lyme disease, or fibromyalgia. Subjects with Sjogren’s disease associated with RA are eligible. b. Any conditions significantly affecting the nervous system if it may interfere with the Investigator’s assessment on disease activity scores including joint counts c. Severe physical incapacitation, or who cannot benefit from medication d. Any other serious acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study 6. Subject who currently has one or more of the following medical conditions which in the opinion of the Investigator would put the subject at risk by participating in the protocol: a. Uncontrolled diabetes mellitus, even after insulin treatment b. Uncontrolled hypertension (as defined by systolic blood pressure =160
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of select (100 mg twice daily [BID], 200 mg BID, and 400 mg BID) doses of SKI-O-703 compared with placebo;Secondary Objective: To evaluate the efficacy on other clinical endpoints of select (100 mg BID, 200 mg BID, and 400 mg BID) doses of SKI-O-703 compared with placebo To evaluate the safety and tolerability of select (100 mg BID, 200 mg BID, and 400 mg BID) doses of SKI-O-703 compared with placebo To investigate the pharmacokinetic (PK) profile of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) To evaluate the effects of SKI-O-703 on exploratory pharmacodynamic (PD) biomarkers ;Primary end point(s): Mean change from baseline in disease activity score for 28 joints (DAS28) using hsCRP score at Week 12;Timepoint(s) of evaluation of this end point: at Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints will be evaluated at Weeks 2, 4, 8 and 12 unless otherwise stated. • Percentage of subjects who would achieve ACR20, ACR50 and ACR70 response over time • Change from baseline in DAS28-hsCRP score • Change from baseline in the tender/painful and swollen joint count (28) • Change from baseline in the physician global assessment of disease activity by visual analog scale (VAS) • Change from baseline in the subject global assessment of disease activity by VAS • Change from baseline in the subject’s assessment of arthritis pain by VAS • Change from baseline in the health assessment questionnaire - disability index (HAQ-DI) • Change from baseline in median hsCRP values at each visit ;Timepoint(s) of evaluation of this end point: at Weeks 2, 4, 8 and 12 unless otherwise stated | — |
Countries
Czech Republic, Korea, Republic of, Poland, Russian Federation, Serbia, Ukraine, United States
Contacts
Public ContactClinical Trials Information
Oscotec Inc.
Outcome results
None listed