Rheumatoid arthritis MedDRA version: 12.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: GSK315234 Injection 100mg/mL
Product Code: GSK315234
Pharmaceutical Form: Injection*
Current Sponsor code: GSK315234
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type:
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females between 18 and 75 years of age, inclusive 2. Using acceptable contraception to ensure that no pregnancies occur during the course of the study and for at least 12 weeks after receiving the last dose for male subjects and for 32 weeks after receiving the last dose for female subjects (see Section 8.1 of the protocol on contraception for more details) 3. Body mass index within the range 18.5 - 35 kg/m2 inclusive 4. Capable of giving informed consent and can comply with the study requirements and timetable 5. Diagnosis of RA according to the revised 1987 criteria of the ACR 6. DAS28 disease activity score of greater than 3.2 at screening and prior to dosing 7. CRP level >0.5 mg/dL at screening and prior to dosing 8. Inflamed knee or ankle, as shown by clinical examination or ultrasound 9. Has never received a biological (marketed compounds or experimental treatments) or has been treated with a biological and failed due to lack of efficacy (adequate wash-out is required based on the half-life of the previously administered biological; wash-out time should be discussed with GSK Medical Monitor) 10. Must have received at least three months of methotrexate (MTX) prior to screening and must be on a stable dose of MTX (up to 25 mg/week) for at least four weeks prior to randomization and be willing to remain on this dose throughout the study 11. Must be on a stable dose of folate supplements (a minimum of 5 mg/week) for at least four weeks prior to randomization and throughout the course of the study 12. If sulfasalazine is being taken in addition to MTX, the subject must be on a stable dose for at least four weeks prior to screening and be willing to remain on this dose throughout the study 13. If hydoxychloroquine or chloroquinine is being taken in addition to MTX, the subject must be on a stable dose for at least three months prior to screening and be willing to remain on this dose throughout the study 14. If other oral anti-rheumatic therapies are being taken [e.g., non steroidal anti inflammatory drugs (NSAIDs), cyclo-oxygenase type -2 (COX-2) inhibitors, oral glucocorticoids (e.g. prednisolone =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination, or ECG (12-lead or Holter); at the discretion of the investigator 2. Positive Hepatitis B surface antigen or Hepatitis C antibody at screening 3. History of human immunodeficiency virus or other immunodeficiency disease at screening 4. A history of elevated liver function tests on more than one occasion (ALT, AST and ALP > 3 times the ULN; total bilirubin > 1.5 times the ULN) in the 6 months prior to screening 5. Previous exposure or past infection caused by mycobacterium tuberculosis, unless adequately treated (documentation of treatment must be provided to the investigator and reviewed by the investigator and GSK Medical Monitor) 6. An acute infection 7. A history of repeated, chronic or opportunistic infections that, in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as a participant in this trial 8. A history of malignancy, except for adequately treated, non-invasive cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix (an exception would be adequately treated cancer >10 years prior to screening; documentation of treatment must be provided to the investigator and reviewed by the investigator and GSK Medical Monitor) 9. Calculated creatinine clearance< 50mL/min 10. Significant cardiac, pulmonary, metabolic, renal, hepatic or GI conditions that, in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as a participant in this trial 11. Has taken cyclosporine, leflonomide, cyclophosphamide or azathioprine within one month of screening. Subjects who have taken cyclosporine, leflonomide, cyclophophamide or azathioprine in the past must have recovered from all drug related AEs. 12. Has taken gold salts or d-penicillamine within one month prior to screening. Subjects that have taken gold salts or d-penicillamine in the past must have recovered from all drug related AEs. 13. Has received intra-articular or intra-muscular glucocorticoids within one month of screening 14. Has received cell-depleting therapy (e.g., rituximab) 15. Has received a live vaccine within three months of dosing 16. Recent history (within six months of screening) of bleeding disorders, anaemia, peptic ulcer disease, haematemesis or GI bleeding 17. Serum iron AND ferritin below the lower limit of the reference range at screening and prior to dosing 18. History of B12 or folate deficiency 19. A history of haematological disease or acquired platelet disorders, including drug-induced thrombocytopaenia, acute idiopathic thrombocytopaenia or von Willebrand’s disease 20. A known risk of intra-cranial hemorrhage including central nervous system surgery within 12 months prior to screening, arterial vascular malformations, aneurysms, significant closed head trauma within 6 months prior to screening or any other incident the investigator and/or medical monitor considers to be relevant 21. Hb <10 g/dL and platelet count < 150 x 10 power9 /L 22. Donation of blood in excess of 500 mL within a 56 day period prior to dosing 23. An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the male subject to use a condom with spermicide in addition to having their female partner use another form of contraception [such as an intra-uterine device (IUD), diaphragm, oral contr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the change in inflammatory biomarkers in the synovial tissue of subjects with rheumatoid arthritis (RA) on a background of methotrexate after administration of a single, intravenous dose of GSK315234, as compared to placebo 2. To assess the safety and tolerability of a single, intravenous dose of GSK315234 in subjects with RA on a background of methotrexate, as compared to placebo, under the conditions of this study ;Secondary Objective: 1. To assess the change in bone and synovial parameters (as measured by MRI) in subjects with RA on a background of methotrexate after administration of a single, intravenous dose of GSK315234 or placebo 2. To assess pharmacodynamic activity (as measured by effects on serum/plasma and urine biomarkers) in subjects with RA on a background of methotrexate after administration of a single, intravenous dose of GSK315234 or placebo 3. To assess clinical activity (as measured by effects on rheumatological endpoints) in subjects with RA on a background of methotrexate after administration of a single, intravenous dose of GSK315234 or placebo 4. To assess pharmacokinetic/pharmacodynamic correlations in subjects with RA on a background of methotrexate after administration of a single, intravenous dose of GSK315234 5. To assess the immunogenicity of GSK315234 in subjects with RA on a background of methotrexate after administration of a single, intravenous dose of GSK315234 ;Primary end point(s): • Synovial infiltration of sub-lining CD68+ macrophage, expressed as change relative to baseline • Spontaneous and elicited adverse events (AEs), vital signs, electrocardiograms (ECGs) and clinical laboratory values | — |
Countries
Belgium, France, Ireland, United Kingdom
Outcome results
None listed