Rheumatoid Arthritis MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: GSK315234
Product Code: GSK315234
Pharmaceutical Form: Injection*
Current Sponsor code: GSK315234
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentratio
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females between 18 and 75 years of age, inclusive. 2. All subjects must use acceptable contraception to ensure that no pregnancies occur during the course of the study and for at least 12 weeks after dosing for males and for 32 weeks after dosing for females. 3. Body mass index within the range 18.5 - 35 kg/m2 inclusive, in addition to a weight range of 55 - 95kg. 4. Subject must be capable of giving informed consent and can comply with the study requirements and timetable. 5. Subject must have a diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology (ACR). 6. Subject must have a DAS28 disease activity score of greater than 4.2 at screening and pre-dose. 7. Subject must have a CRP serum level of =0.5mg/dl or an ESR level =28mm/hour at screening and pre-dose 8. Subject has NOT received any biological therapy in the past, including biologicals for the treatment of RA. 9. Subject must have liver function tests including alanine transaminase (ALT) and aspartate transaminase (AST) within 1.5 times the upper limit of normal (ULN) and alkaline phosphatase (ALP) within 3 times ULN at screening. The patient must also have total bilirubin within the ULN at screening. 10. Subject must have received at least 3 months of methotrexate and must be on a stable dose of MTX (up to 25 mg/week) for at least 8 weeks prior to screening and be willing to remain on this dose throughout the study. 11. If sulfasalazine is being taken in addition to MTX, subject must be on a stable dose for at least 4 weeks prior to screening and be willing to remain on this dose throughout the study. 12. If hydoxychloroquine or chloroquinine is being taken in addition to MTX, subject must be on a stable dose for at least 3 months prior to screening and be willing to remain on this dose throughout the study. 13. Those subjects on other oral anti-rheumatic therapies, which may include NSAIDs, COX-2 inhibitors, oral glucocorticoids e.g. prednisolone (=10mg/day) must be on stable dosing regimens for at least 4 weeks prior to screening and be willing to remain on this regime throughout the study. Subjects receiving i.m. glucocorticoids e.g methylprednisolone (=120 mg/month) must be on a stable dosing regimen for at least 3 months prior to screening and be willing to remain on this regimen throughout the study. 14. Subject must be on a stable dose of folate supplements (5 mg/week) for at least 4 weeks prior to dosing and throughout the course of the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=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 (e.g. haematology parameter outside the normal limits), or ECG (12 Lead or Holter). 2. Subject has a positive Hepatitis B surface antigen or Hepatitis C antibody result at screening. 3. Subject has a history of elevated liver function tests on more than one occasion (ALT, AST and ALP > 3 x Upper Limit of Normal (ULN); total bilirubin > 1.5 x ULN) in the past 6 months. 4. Previous exposure or past infection caused by Mycobacterium tuberculosis 5. Subject has an acute infection. 6. Subject has 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. 7. Subject has a history of malignancy, except for surgically cured basal cell carcinoma or females with cured cervical carcinoma (> 2 yrs prior). 8. Subject has a history of human immunodeficiency virus (HIV) or other immunodeficiency disease. 9. Subject whose calculated creatinine clearance is less than 50ml/min 10. Subject has significant cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal 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. Subject has taken cyclosporine, leflonomide, cyclophophamide or azathioprine within 1 month of screening. Subjects that have taken cyclosporine, leflonomide, cyclophophamide or azathioprine in the past must have recovered from all drug related adverse events. 12. Subject has taken gold salts or d-penicillamine within 1 month prior to screening. Subjects that have taken gold salts or d-penicillamine in the past must have recovered from all drug related adverse events. 13. Subject has received intra-articular glucocorticoids within 1 month of screening. 14. Recent history of bleeding disorders, anaemia, peptic ulcer disease, haematemesis or gastrointestinal bleeding 15. Subjects with a history of haematological disease or acquired platelet disorders, including drug-induced thrombocytopaenia, acute idiopathic thrombocytopaenia or von Willebrand’s disease. 16. Subjects with a known risk of intra-cranial haemorrhage including Central Nervous System surgery within the last 12 months, arterial vascular malformations, aneurysms, significant closed head trauma within 6 months or any other incident the investigator and/or medical monitor considers to be relevant. 17. Subect has Hb <10 g/deciliter (dL) and platelet count < 150 x 109/Liter (L) 18. Donation of blood in excess of 500 ml within a 56 day period prior to dosing 19. 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 interuterine device (IUD), diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants of levonorgestrel or a tubal ligation if the woman could become pregnant for at least 12 weeks after dosing. 20. An unwillingness of female subject of child bearing potential to use adequate contraception, as defined in the study restriction section. If necessary, women of non-child bearing potential (i.e. post-menopausal or surgically sterile e.g. tubal ligation or hysterectomy or bilateral oophor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess: 1) safety and tolerability of GSK315234A after single and repeat i.v. infusions in subjects with active RA on background of methotrexate (MTX). 2) effect of GSK315234A on disease activity (as defined by DAS28 score) on Day 28 after a single i.v. infusion in subjects with active RA on background of MTX. ;Secondary Objective: To assess: 1) PK of GSK315234A after single and repeat i.v. infusions in subjects with active RA on background MTX. 2) effect of GSK315234A on disease activity (as defined by DAS28 score) after repeat i.v. infusions in subjects with active RA on background of MTX. 3) effect of GSK315234A on disease activity (as defined by EULAR and ACR20, 50 and 70 score) after single and repeat i.v. infusions in subjects with active RA on background MTX. 4) effect of GSK315234A on fatigue (as defined by MAF) after single and repeat i.v. infusions in subjects with active RA on background MTX. 5) PD activity (biomarkers) of GSK315234A after single and repeat i.v. infusions in subjects with active RA on background MTX. 6) PK/PD correlations of GSK315234A after a single and repeat i.v. infusions in subjects with active RA on background MTX. 7) immunogenicity of GSK315234A single and repeat i.v. infusions in subjects with active RA on background MTX. ;Primary end point(s): 1) Safety assessments: i) Adverse events ii) Vital signs (HR, BP) iii) ECG iv) Clinical laboratory tests (haematology, biochemistry and urinalysis) 2) DAS28 scores on Day 28 after single intravenous dose | — |
Countries
United Kingdom
Outcome results
None listed