A Study to Investigate the Ability of GSK706769 to Maintain Clinical Remission After Withdrawal of Enbrel in Rheumatoid Arthritis Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 29 January 2024
• Main ID: NCT00979771
• Date of registration: 17/09/2009
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Study to Investigate the Ability of GSK706769 to Maintain Clinical Remission After Withdrawal of Enbrel in Rheumatoid Arthritis Patients
• Scientific 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
• Date of first enrolment: February 1, 2010
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/ct2/show/NCT00979771
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Netherlands

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Arthritis, Rheumatoid

Intervention(s)

Drug: Placebo

Drug: GSK706769

Primary Outcome(s)

Maintenance of clinical remission after withdrawal of Enbrel in patients with RA, as determined by DAS28 scores. [Time Frame: Day 28 after first dose administration]

Secondary Outcome(s)

Safety and tolerability of GSK706769 following repeat dosing in RA subjects for up to 28 days [Time Frame: After first dose administration]

To investigate the time to relapse following withdrawal of Enbrel [Time Frame: After first dose administration]

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. [Time Frame: Day 28 and 28 days after last dose of study medication]

Pharmacokinetics (PK) of GSK706769, and its metabolite GSK1996847A [Time Frame: 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 [Time Frame: Day 1, 14 and 28 after first dose administration]

Rheumatological assessments, pain, fatigue and physical functioning following repeat dosing with GSK706769 for up to 28 days [Time Frame: Day 1, 14, 28, 56 after first dose administration]

Secondary ID(s)

2009-012204-42

112145

Source(s) of Monetary Support

Please refer to primary and secondary sponsors