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

NCT00979771 | Withdrawn Phase 2

• 2 other identifiers: 1121452009-012204-42
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Arthritis, Rheumatoid

Keywords

GSK706769; Enbrel; Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Maintenance of clinical remission after withdrawal of Enbrel in patients with RA, as determined by DAS28 scores.

  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.

  Day 28 and 28 days after last dose of study medication

• To investigate the time to relapse following withdrawal of Enbrel

  After first dose administration

• Safety and tolerability of GSK706769 following repeat dosing in RA subjects for up to 28 days

  After first dose administration

• Rheumatological assessments, pain, fatigue and physical functioning following repeat dosing with GSK706769 for up to 28 days

  Day 1, 14, 28, 56 after first dose administration

• Pharmacokinetics (PK) of GSK706769, and its metabolite GSK1996847A

  Day 1, 14 and 28 after first dose administration

Study Arms (2)

GSK706769

EXPERIMENTAL

100 mg GSK706769 twice daily orally (BID) for 28 days

Drug: GSK706769

Placebo

PLACEBO COMPARATOR

GSK706769 matched-placebo twice daily orally (BID) for 28 days

Drug: Placebo

Interventions

GSK706769 DRUG

100 mg GSK706769 twice daily orally (BID) for 28 days

GSK706769

Placebo DRUG

GSK706769 matched-placebo twice daily orally (BID) for 28 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%).

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Amsterdam, 1105 AZ, Netherlands

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2009
• First Posted: September 18, 2009
• Study Start: February 1, 2010
• Primary Completion: April 28, 2011
• Study Completion: April 28, 2011
• Last Updated: January 22, 2024

Record last verified: 2024-01

Locations

NL (1)