Last updated: 01/19/2024 16:30:33
A study to investigate the ability of GSK706769 to maintain clinical remission after withdrawal of Enbrel in rheumatoid arthritis patients
GSK study ID
112145
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
Official title: A randomized, double-blind, placebo-controlled, parallel group study to investigate the ability of GSK706769 to maintain clinical remission after withdrawal of Enbrel in patients with rheumatoid arthritis
Trial description: The purpose of this study is to determine if GSK706769 can maintain clinical remission established by Enbrel after withdrawal of Enbrel in rheumatoid arthritis patients.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Maintenance of clinical remission after withdrawal of Enbrel in patients with RA, as determined by DAS28 scores.
Timeframe: Day 28 after first dose administration
Secondary outcomes:
The ability of GSK706769 to maintain clinical remission after withdrawal of Enbrel in patients with RA, as determined by the Patient Global Assessment scores and evidence of swollen or tender joints.
Timeframe: Day 28 and 28 days after last dose of study medication
To investigate the time to relapse following withdrawal of Enbrel
Timeframe: After first dose administration
Safety and tolerability of GSK706769 following repeat dosing in RA subjects for up to 28 days
Timeframe: After first dose administration
Rheumatological assessments, pain, fatigue and physical functioning following repeat dosing with GSK706769 for up to 28 days
Timeframe: Day 1, 14, 28, 56 after first dose administration
Pharmacokinetics (PK) of GSK706769, and its metabolite GSK1996847A
Timeframe: Day 1, 14 and 28 after first dose administration
CCR5 receptor occupancy (RO) in peripheral blood following repeat dosing with GSK706769 for up to 28 days, as feasible
Timeframe: Day 1, 14 and 28 after first dose administration
Interventions:
Enrollment:
0
Primary completion date:
2011-28-04
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Arthritis, Rheumatoid
Product
GSK706769
Collaborators
GSK
Study date(s)
February 2010 to April 2011
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Male or female over 18 years of age, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of child-bearing potential and agrees to use one of the contraception methods listed in the protocol for an appropriate period of time Female subjects must agree to use contraception until 4 days post-last dose.
- The subject is using oral prednisolone at doses > 10mg/day.
- The subject’s NSAID or glucocorticoid dosing regimen has changed during the 4 weeks prior to randomisation.
Inclusion and exclusion criteria
Inclusion criteria:
- Male or female over 18 years of age, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of child-bearing potential and agrees to use one of the contraception methods listed in the protocol for an appropriate period of time Female subjects must agree to use contraception until 4 days post-last dose.
- Body weight greater than or equal to 50 kg and BMI within the range 19 – 32 kg/m2.
- The subject has a diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology (ACR) and has been treated with an anti TNF-alpha agent for < 2 years.
- The subject is taking Enbrel for at least 6 months prior to enrollment.
- The subject is willing to stop taking Enbrel for 56 days.
- The subject is in clinical remission, defined as DAS28 less than or equal to 2.6 and has been for the preceding 6 months.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Average QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
- AST and ALT < 2xULN; alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Exclusion criteria:
- The subject is using oral prednisolone at doses > 10mg/day.
- The subject’s NSAID or glucocorticoid dosing regimen has changed during the 4 weeks prior to randomisation.
- The subject’s receiving DMARDs other than Enbrel and methotrexate.
- The subject’s current methotrexate regimen has changed significantly (i.e. likely to impact disease activity during the study period) within the 3 months prior to dosing e.g. changes in dose of greater than 2.5mg.
- Use of CYP3A4 inhibitors/inducers within 14 days prior to dosing and CYP3A4 substrates with a narrow therapeutic index within 7 days prior to dosing.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Absolute neutrophil count < 1500/ul.
- History of sensitivity to the study medication, or components thereof or a history of drug or other allergy that contraindicates their participation.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug screen, unless the subject is receiving a prescribed medication that could give a positive in the drug screen and prior to the screen being sent the medication has been discussed and pre-approved by the medical monitor.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined by the protocol.
- The subject has an acute infection or a history of repeated or chronic infections.
- The subject has significant cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions that in the opinion of the investigator and/or medical monitor, places the subject at an unacceptable risk as a participant in this trial.
- Subjects with autoimmune hemolytic anemia or G6PD deficiency.
- Malignancy in the past 2 years, except for adequately treated non-invasive cancers of the skin.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- Consumption of grapefruit, grapefruit juice or grapefruit hybrids within 7 days prior to the first dose of study medication.
Trial location(s)
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
Other
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
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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