Arthritis, RheumatoidPhase 2NCT00979771
A Study to Investigate the Ability of GSK706769 to Maintain Clinical Remission After Withdrawal of Enbrel in Rheumatoid Arthritis Patients
A Phase 2 study testing GSK706769 in people with Arthritis, Rheumatoid, run by GlaxoSmithKline at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthritis, Rheumatoid
- What is being tested?
- GSK706769
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Feb 2010to 28 Apr 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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%).
Who cannot join
- 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).
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- 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 locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
This study is a phase II, randomized, double-blind, placebo-controlled, parallel group study in subjects with rheumatoid arthritis (RA) on stable doses of Enbrel. Subjects with an adequate response to Enbrel will be enrolled into the study. Subjects will be withdrawn from their Enbrel and randomized to receive 28 days of dosing with either GSK706769 or placebo followed by 28 days off-drug. This study is exploring a novel therapeutic paradigm for RA, remission maintenance. In such an approach, remission is induced and then the inducing agent is stopped and a maintenance agent is added. The clinical benefit would be derived from the fact that the remission agent may be easier to take (e.g. oral rather than parenteral), more durable in its maintenance of remission, and/or safer (e.g. no TB reactivation). This study directly explores remission maintenance. Specifically, in a randomised, double blind, placebo controlled study, RA patients in remission through an adequate response to Enbrel will be recruited. Enbrel has been selected as it has a relatively short half life and therefore it is more likely patients treated with placebo may have a higher incidence of relapse after 28 days than with other anti-TNF treatments. After withdrawal of Enbrel (and possibly other oral DMARDs), subjects will be randomised to receive GSK706769 or placebo for 28 days followed by a period of 28 days off treatment. It is hypothesized that GSK706769 will prevent any CCR5+ cells from returning into the synovium, thereby resulting in maintenance of the efficacy induced by Enbrel. In the placebo group, CCR5 cells may re-populate the synovium resulting in increased inflammation. Patients experiencing increased disease activity will be able to withdraw from the study and resume standard of care.
- Conditions
- Arthritis, Rheumatoid
- Being tested
- GSK706769, Placebo
- Keywords
- GSK706769, Enbrel, Rheumatoid Arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK706769Drug
100 mg GSK706769 twice daily orally (BID) for 28 days
PlaceboDrug
GSK706769 matched-placebo twice daily orally (BID) for 28 days
| Study group | Role | What they receive |
|---|---|---|
| GSK706769 | Experimental | 100 mg GSK706769 twice daily orally (BID) for 28 days Receives: Drug: GSK706769 |
| Placebo | Placebo comparator | GSK706769 matched-placebo twice daily orally (BID) for 28 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maintenance of clinical remission after withdrawal of Enbrel in patients with RA, as determined by DAS28 scores.
Measured: Day 28 after first dose administration
Secondary outcomes (6)
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.
Measured: Day 28 and 28 days after last dose of study medication
To investigate the time to relapse following withdrawal of Enbrel
Measured: After first dose administration
Safety and tolerability of GSK706769 following repeat dosing in RA subjects for up to 28 days
Measured: After first dose administration
Rheumatological assessments, pain, fatigue and physical functioning following repeat dosing with GSK706769 for up to 28 days
Measured: Day 1, 14, 28, 56 after first dose administration
Pharmacokinetics (PK) of GSK706769, and its metabolite GSK1996847A
Measured: 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
Measured: Day 1, 14 and 28 after first dose administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2009 (estimated)
- Study start1 Feb 2010 (estimated)
- Primary completion28 Apr 2011 (estimated)
- Study completion28 Apr 2011 (estimated)
Why it stopped: Cancelled Before Active
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00979771
- Sponsor's protocol ID
- 112145
- Other IDs
- 2009-012204-42, 2009
- Status last verified
- Jan 2024
- First submitted
- 17 Sep 2009
- Last updated
- 22 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00979771
- Acronym / sponsor ID
- 112145
- Conditions
- Arthritis, Rheumatoid
- Keywords
- GSK706769, Enbrel, Rheumatoid Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Cancelled Before Active
- Enrolment
- 0 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Feb 2010 (estimated)
- Primary completion
- 28 Apr 2011 (estimated)
- Study completion
- 28 Apr 2011 (estimated)
- First posted
- 18 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study is a phase II, randomized, double-blind, placebo-controlled, parallel group study in subjects with rheumatoid arthritis (RA) on stable doses of Enbrel. Subjects with an adequate response to Enbrel will be enrolled into the study. Subjects will be withdrawn from their Enbrel and randomized to receive 28 days of dosing with either GSK706769 or placebo followed by 28 days off-drug. This study is exploring a novel therapeutic paradigm for RA, remission maintenance. In such an approach, remission is induced and then the inducing agent is stopped and a maintenance agent is added. The clinical benefit would be derived from the fact that the remission agent may be easier to take (e.g. oral rather than parenteral), more durable in its maintenance of remission, and/or safer (e.g. no TB reactivation). This study directly explores remission maintenance. Specifically, in a randomised, double blind, placebo controlled study, RA patients in remission through an adequate response to Enbrel will be recruited. Enbrel has been selected as it has a relatively short half life and therefore it is more likely patients treated with placebo may have a higher incidence of relapse after 28 days than with other anti-TNF treatments. After withdrawal of Enbrel (and possibly other oral DMARDs), subjects will be randomised to receive GSK706769 or placebo for 28 days followed by a period of 28 days off treatment. It is hypothesized that GSK706769 will prevent any CCR5+ cells from returning into the synovium, thereby resulting in maintenance of the efficacy induced by Enbrel. In the placebo group, CCR5 cells may re-populate the synovium resulting in increased inflammation. Patients experiencing increased disease activity will be able to withdraw from the study and resume standard of care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GSK706769 | Experimental | Drug: GSK706769100 mg GSK706769 twice daily orally (BID) for 28 days |
| Placebo | Placebo comparator | Drug: PlaceboGSK706769 matched-placebo twice daily orally (BID) for 28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK706769100 mg GSK706769 twice daily orally (BID) for 28 days | Drug | GSK706769 |
| PlaceboGSK706769 matched-placebo twice daily orally (BID) for 28 days | Drug | Placebo |
Primary outcome
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
6 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.
Time frame: Day 28 and 28 days after last dose of study medication
To investigate the time to relapse following withdrawal of Enbrel
Time frame: After first dose administration
Safety and tolerability of GSK706769 following repeat dosing in RA subjects for up to 28 days
Time frame: 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
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK706769 in people with Arthritis, Rheumatoid, run by GlaxoSmithKline at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2024.