Rheumatoid Arthritis MedDRA version: 19.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years at the time of signing informed consent. 2. Meets ACR/EULAR 2010 RA Classification Criteria. 3. Functional class I, II or III defined by the 1992 ACR Classification of Functional Status in RA. 4. Disease duration of =12 weeks (time from onset of patient-reported symptoms of either pain or stiffness or swelling in hands, feet or wrists). 5. Swollen joint count of =4 (66-joint count) and tender joint count of =4 (68-joint count) at screening and at Day 1. 6. DAS28(CRP) =3.2 at screening and DAS28(ESR) =3.2 at Day 1. 7. C-Reactive Protein (CRP) =5.0 mg/L at screening. 8. Must have previously received MTX (15-25 mg weekly) for at least 12 weeks before screening, with no change in route of administration, with a stable and tolerated dose for =4 weeks prior to Day 1. A stable dose of MTX =7.5 mg/week is acceptable, if the MTX dose has been reduced for reasons of documented intolerance to MTX, e.g. hepatic or hematologic toxicity, or per local requirement. 9. Weight =45 kg. 10. Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria detailed in Appendix 12.2. 11. Written informed consent prior to any of the screening procedures including discontinuation of prohibited medications. 12. Willing to continue or initiate treatment with oral folic acid (at least 5 mg/week) or equivalent and be treated during the entire study (mandatory co-medication for MTX treatment). 13. Diffusing capacity of the lung for carbon monoxide (DLCO) =60% (a,b) predicted; forced expiratory volume in 1 second (FEV1) =70% predicted. a. Screening and Day 1 values within 10% of each other (the test may be repeated twice within the screening period, i.e. subjects may undergo a total of three DLCO tests during the screening period). b. For subjects with DLCO values >60% to =65 years) yes F.1.3.1 Number of subjects for this age range 31
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating women. 2. History of other inflammatory rheumatological or autoimmune disorders, other than Sjögren’s syndrome secondary to RA. 3. History of any respiratory disease which (in the opinion of the investigator) would compromise subject safety or the ability of the subject to complete the study (e.g. significant interstitial lung disease, such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), moderate-severe asthma, bronchiectasis, previous PAP). 4. Clinically-significant or unstable (in the opinion of the investigator) persistent cough or dyspnea that is unexplained. 5. QTc >450msec or QTc >480msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia’s formula (QTcF). 6. Liver function tests: alanine aminotransferase (ALT) >1.5x upper limit of normal (ULN); aspartate transaminase (AST) >1.5 upper limit of normal; alkaline phosphatase and bilirubin =1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 1.5xULN within 28 days of Day 1. 11. Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency. 12. History of infected joint prosthesis at any time, with the prosthesis still in situ. History of leg ulcers, catheters, chronic sinusitis or recurrent chest or urinary tract infections. 13. Active infections, or history of recurrent infections (excluding recurrent fungal infections of the nail bed), or have required management of acute or chronic infections, as follows: a. Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria). OR b. Hospitalization for treatment of infection within 26 weeks of Day 1. OR c. Use of parenteral (IV or IM) antimicrobials (antibacterials, antivirals, antifungals, or antiparasitic agents) within 26 weeks of Day 1 or oral antimicrobials within 14 days of Day 1. 14. A vaccination (live or attenuated) within 30 days of Day 1 or BCG vaccination within 365 days of Day 1, or a live vaccination planned during the course of the study. 15. Any surgical procedure, including bone or joint surgery/synovectomy within 12 weeks prior to Day 1 or any planned surgery within the duration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of GSK3196165;Primary end point(s): Proportion of subjects who achieve DAS28(CRP) remission (DAS28(CRP) <2.6) ;Timepoint(s) of evaluation of this end point: At Week 24;Secondary Objective: To assess - Dose-efficacy response of GSK3196165 - Safety - Population pharmacokinetics - Pharmacodynamics - Novel biomarkers: - To examine the molecular profiles of blood samples to identify factors that may influence biological and clinical responses to GSK3196165 and/or associated with the development or progression of RA or medically related conditions | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Please refer to section E.5.2;Secondary end point(s): Major Secondary Efficacy Endpoints - Change from baseline in DAS28(CRP) at Week 12 (to support dose response evaluation). - Proportion of subject achieving DAS28(CRP) remission at all assessment timepoints. - Change from baseline in DAS28(CRP) at all assessment timepoints. - Time to first DAS28(CRP) remission. - Proportion of subjects achieving categorical DAS28(CRP) response (moderate/good EULAR response) at all assessment timepoints. - ACR 20/50/70 response rates at all assessment timepoints. - Index- and Boolean-based ACR/EULAR remission rates, and CDAI remission rate at all assessment timepoints. - Change from baseline in SDAI and CDAI at all assessment timepoints. - Change from baseline in HAQ-DI score at all assessment timepoints. - Change from baseline in pain score at all assessment timepoints. - Change from baseline in physical and mental component scores and in domain scores of SF-36 at all assessment timepoints. - Change from baseline in FACIT-Fatigue at all assessment timepoints. - Change from baseline in BFI Question 3 at all assessment timepoints. Major Secondary Safety Endpoints - Incidence of adverse events and serious adverse events. - Incidence of infections. - Incidence of pulmonary events. | — |
Countries
Argentina, Bulgaria, Canada, Czech Republic, Estonia, Germany, Hungary, Italy, Mexico, Poland, Russian Federation, South Africa, Spain, Ukraine, United Kingdom
Contacts
Public ContactGSK Clinical Support HelpDesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed