Last updated: 11/04/2018 10:22:10
A Study To Investigate The Effect Of 28 Days Of Dosing With GW856553 On Patients With Rheumatoid Arthritis
GSK study ID
RA3103718
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A randomized, double blind, placebo controlled study to investigate the safety and tolerability and clinical activity of 28 days of oral repeat dosing with GW856553 at 7.5mg BID in subjects with active rheumatoid arthritis on stable anti-rheumatic therapy.
Trial description: This study is designed to look at the safety, tolerability and effectiveness of 28 days of dosing of GW856553 in rheumatoid arthritis patients.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Mean Disease Activity Score based on 28 joint count (DAS28)
Timeframe: Up to 56 days
Secondary outcomes:
Number of participants with any adverse events (AEs) and seroius adverse events (SAEs)
Timeframe: Up to Day 84
Number of participants with vital signs of potential clinical importance (PCI) during treatment
Timeframe: Up to Day 56
Number of participants with vital signs of PCI during treatment
Timeframe: Up to day 84
Number of participants with abnormal clinically significant electrocardiogram (ECG) findings during treatment
Timeframe: Up to Day 56
Number of participants with abnormal clinically significant ECG findings during treatment
Timeframe: Up to Day 84
Number of participants with abnormal hematology data of PCI during treatment
Timeframe: Up to Day 56
Number of participants with abnormal hematology data of PCI during treatment
Timeframe: Up to Day 84
Number of participants with abnormal clinical chemistry data of PCI
Timeframe: Up to Day 56
Number of participants with abnormal clinical chemistry data of PCI
Timeframe: Up to Day 84
Number of participants with American College of Rheumatology (ACR)-defined improvements of 20%, 50% and 70%
Timeframe: Day 28 of each period (up to Day 56)
Number of participants meeting the European League against Rheumatism (EULAR) Response Criteria
Timeframe: Day 15 and Day 28 of period 1
Mean Tender/Painful Joint Count
Timeframe: Day 15 and Day 28 of period 1 and period 2
Mean swollen joints (SJC): 28 joint count
Timeframe: Day 15 and Day 28 of period 1
Mean participants assessment of pain
Timeframe: Day 15 and 28 of period 1
Mean ESR
Timeframe: Day 15 and 28 of period 1
Mean C-reactive protein (CRP) data
Timeframe: Day 15 and 28 of period 1
Duration of morning stiffness
Timeframe: Up to Day 84
Participant's and Physician's Global Assessment of Disease Activity
Timeframe: Up to day 84
Functional Disability Index (Health assessment questionnaire –[HAQ])
Timeframe: Up to day 84
Multidimensional Assessment of Fatigue (MAF)
Timeframe: Up to Day 84
Mean plasma level of biomarkers- Interleukin 6 (IL-6), B-lymphocyte chemoattractant (BLC), and Tumour necrosis factor-alpha (TNF-A)
Timeframe: Day 15 and 28 of period 1
Plasma level of biomarker- Serum Amyloid A (SAA)
Timeframe: Day 15 and 28 of period 1
Mean plasma level of biomarker- Matrix metalloprotienases (MMP3)
Timeframe: Day 15 and 28 of period 1
Measurement of exploratory biomarkers of cartilage damage, bone formation and bone resorption
Timeframe: Day 15 and 28 of period 1
Whole blood levels of mRNA for the following genes: Inducible nitric oxide synthase (iNOS), Cyclo-oxygenase-2 (cox-2), TNF-A, IL-8, IL-6 and IL-1 beta.
Timeframe: Day 15 and 28 of period 1
Exploratory whole blood transcriptional profiles
Timeframe: Day 15 and 28 of period 1
DAS28 on Day 28 versus GW856553 Exposure
Timeframe: Day 28
ACR20 response on Day 28 versus GW856553 Exposure
Timeframe: Day 28
Population pharmacokinetic (PK) analysis
Timeframe: Day 15 and 28 of period 1
MRI data: Ramris Score, Total Bone Erosion Score, Total Synovium Score
Timeframe: Day 28
MRI data: Total Synovium Volume
Timeframe: Day 28
Summary of participants with bone oedema volume
Timeframe: Days 1 and 28
X-ray data: total erosion score, total joint space narrowing score and total x-ray score
Timeframe: Day 1
Interventions:
Drug: GW856553
Enrollment:
57
Observational study model:
Not applicable
Primary completion date:
2008-21-01
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Arthritis, Rheumatoid
Product
losmapimod
Collaborators
Not applicable
Study date(s)
October 2006 to January 2008
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- The subject is male or female ≥ 18 years of age.
- To be eligible, female subjects must have a negative pregnancy test (i.e. serum beta
- The subject has a three month prior history of regular alcohol consumption exceeding
- an average weekly intake of > 21 units (or an average daily intake of greater than 3
Inclusion and exclusion criteria
Inclusion criteria:
- The subject is male or female ≥ 18 years of age.
- To be eligible, female subjects must have a negative pregnancy test (i.e. serum beta hCG test) and be of: a. non-childbearing potential (i.e. physiologically incapable of becoming pregnant). This includes any female who is post-menopausal. For the purposes of this study, post menopausal is defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. Postmenopausal status will be confirmed by serum FSH and oestradiol concentrations at screening. Surgical sterility will be defined as females who have had a hysterectomy and/or bilateral oophorectomy or tubal ligation. OR b. childbearing potential and agrees to commit to one of the protocol-approved methods of contraception as detailed in Section 7.1.
- Body weight ≥ 50 kg (110lbs) for males and ≥ 45 kg (99lbs) for females.
- Body mass index (BMI) within the range 18.5-35.0 kg/m2 inclusive.
- The subject has a diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology (ACR) (see Appendix 6).
- The subject must have DAS28 ≥ 4.2 (DAS28 calculated using ESR).
- The subject must have liver function (ALT, AST and total bilirubin) tests < 1.5 x ULN at screening.
- The subject must have ALP < 2 x ULN at screening.
- The subject must have normal serum folate levels at screening (folate supplements can be administered if required but this must be stable for 4 weeks prior to randomisation).
- The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
- Signed and dated written informed consent prior to admission to the study.
Exclusion criteria:
- The subject has a three month prior history of regular alcohol consumption exceeding an average weekly intake of > 21 units (or an average daily intake of greater than 3 units) for males, or an average weekly intake of > 14 units (or an average daily intake of greater than 2 units) for females. 1 unit is equivalent to a half-pint (284mL) of beer/lager; 25mL measure of spirits or 125mL of wine; or a positive alcohol breath test at the screening visit.
- The subject has any history of liver disease.
- The subject has a positive Hepatitis B surface antigen or Hepatitis C antibody result within 3 months of the start of the study.
- The subject has a history of elevated liver function tests on more than one occasion (ALT, AST, and total bilirubin > 2 x ULN or ALP > 3 x ULN) in the past 7 months.
- The subject is currently receiving a biological anti-rheumatic therapy.
- The subject has failed more than one anti-TNFα biological therapy due to lack of efficacy.
- The subject received an anti-rheumatic biological therapy within 6 months (for i.v. administered therapies with long half-lives e.g. infliximab) or 3 months (for subcutaneously administered therapies or iv administered therapies with short halflives e.g. adalimumab or etanercept) prior to randomisation.
- The subject has received rituximab.
- The subject is using oral prednisolone at doses > 10mg/day, methotrexate > 25 mg/week or sulphasalazine > 5g/day.
- The subject’s DMARD dosing regimen has changed during the 4 weeks prior to randomisation.
- The subject’s current DMARD regimen has changed significantly (i.e. likely to impact disease activity during the study period) within the 3 months prior to dosing e.g. addition of a DMARD, changes in dose of greater than 2.5mg for methotrexate.
- The subject has received leflunomide for less than 6 months prior to randomisation.
- The subject has failed more than 3 DMARDs.
- The subject’s NSAIDs, COX-2 inhibitors or glucocorticoid dosing regimen changes at any time during four weeks prior to randomisation.
- The subject’s statin dosing regimen has changed significantly during the 3 months prior to randomisation
- The 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.
- The subject has an acute infection or a history of repeated or chronic infections.
- The subject has a history of active tuberculosis.
- The subject has a history of malignancy, except for surgically cured basal cell carcinoma or females with cured cervical carcinoma (> 2 yrs prior).
- The subject has a history of HIV or other immunosuppressive disease.
- The subject has participated in a clinical trial within the 3 months prior to the study onset for non-biological therapy; or within 6 months of a biological therapy.
- The subject has Hb < 9 g/dL and platelet count < 150 000/mm3.
- The subject has a calculated creatinine clearance less than 60mL/min (subjects with a calculated creatinine clearance ≥ 50mL/min but < 60mL/min may still be included in consultation with the GSK medical monitor, but will not be eligible for the gadolinium enhancement MRI scans).
- The subject has uncontrolled diabetes or psoriasis.
- The subject has had a joint injection with glucocorticoid within the previous 4 weeks.
- The subject is pregnant or nursing.
- The subject is receiving medication which in the opinion of the investigator and/or GSK medical monitor, would interfere with study procedures, objectives or compromise subject safety.
Trial location(s)
Study documents
No study documents available.
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2008-21-01
Actual study completion date
2008-21-01
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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