A study to assess the efficacy and safety of GSK2586184 in SLE

An adaptive Phase II study to evaluate the efficacy, pharmacodynamics, safety and tolerability of GSK2586184 in patients with active systemic lupus erythematosus.

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2012-001645-41-DE

Enrollment

250

Registered

2012-10-16

Start date

2013-02-19

Completion date

Unknown

Last updated

2014-12-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Systemic Lupus Erythematosus MedDRA version: 16.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Interventions

Product Name: GSK2586184 Product Code: GSK2586184 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: GSK2586184 CAS Number: 1206163-45-2 Current Sponsor code: GSK2586184 Other descriptive na

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Age and Gender: Male or female between 18 and 75 years of age inclusive, at the time of signing the informed consent. 2. SLE classification: Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria, with 4 or more of the 11 ACR criteria present, serially or simultaneously during any interval or observation. 3. Severity of disease: Have clinically active SLE disease defined as a SELENA SLEDAI score =8 at screening during the 35-day screen period. 4. Auto antibodies: Are serologically active having unequivocally positive antinuclear antibody (ANA) or anti-double stranded DNA (anti-dsDNA) antibody test results from 2 independent time points as follows: • Positive test results from 2 independent time points within the study screening period. Screening results must be based on the study’s central laboratory results. A positive test is defined as a positive ANA test equivalent to a titre =1:80 as defined in the central laboratory manual and/or a positive anti-dsDNA (=30 IU/mL) serum antibody. OR • One positive historical test result and 1 positive test result for either ANA or anti-dsDNA during the screening period. Historical documentation of a positive test of ANA (e.g., ANA by HEp-2 titre) or anti-dsDNA antibody (e.g., anti-dsDNA by Farr assay) must include the date and type of the test, the name of the testing laboratory, numerical reference range, and a key that explains values provided as positive vs. negative OR negative, equivocal/borderline positive). Only unequivocally positive values as defined in the laboratory’s reference range are acceptable; borderline values will not be accepted. 5. Treatment for SLE: patient stable on either no treatment or on a stable dose of corticosteroids (=15mg/day prednisone or prednisone equivalent or less) stable for a minimum of 30 days prior to screening and through to Day 0/Randomisation and /or an antimalarial therapy [hydroxychloroquine (=400mg daily dose) or chloroquine (=500mg daily dose) or quinacrine(=100mg daily dose)] for a minimum of 60 days prior to the Day 0/Randomisation Visit. Subjects receiving azathioprine (= 2mg/kg/day or = 150mg/day, whichever is greater) or mycophenolate mofetil (= 1.5g/day), or MTX (=20mg/week), either alone or in addition to steroids and / or antimalarial therapy as described above, if they have been on a stable dose of azathioprine OR mycophenolate mofetil OR MTX for a minimum of 90 days prior to the Day 0 /Randomisation Visit. For those subjects on alternating day dosing of steroids, use the average of 2 daily doses to calculate the average daily steroid dose. 6. ECG: Single QTc, < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block. 7. Prevention of Pregnancy: Females: A female subject is eligible to participate if she is not pregnant, as confirmed by a negative serum human chorionic gonadotrophin (hCG) test, or lactating and at least one of the following conditions applies: Please refer to page 41 bullet point 7 of the study protocol for details. 8. Informed consent: Capable of giving written informed consent, including confirmation that the subject is not mentally or legally incapacitated, and compliance with the requirements and restrictions listed in the consent form. French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a

Exclusion criteria

Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Kidney Disease 2. CNS Disease 3. Alcohol Abuse 4. Substance Abuse 5. Hepatitis B 6. Hepatitis C 7. HIV 8. Previous investigational product exposure 9. Previous and current medication 10. Prior biological therapies 11. Transplantation 12. Uncontrolled Other Diseases 13. Surgery and Other Conditions 14. Cancer 15. Infections 16. Mycobacterium Tuberculosis 17. Haematology 18. Serum immunoglobulin (Ig) levels 19. Liver Function Tests 20. Other laboratory abnormalities 21. Drug sensitivity 22. Blood donation * Please refer to the study protocol section 5.3 Exclusion Criteria pages 43-44 for further details.

Design outcomes

Primary

Measure	Time frame
Main Objective: • To estimate the relationship between dose of GSK2586184 and pharmacodynamic effect on expression of selected messenger ribonucleic acid (mRNA) transcripts following 2 weeks of treatment in SLE patients • To estimate the relationship between dose of GSK2586184 and clinical response as assessed by SELENA SLEDAI score following 12 weeks of treatment in SLE patients • To evaluate the safety and tolerability of repeat doses of GSK2586184 in SLE patients.;Secondary Objective: • To estimate the relationship between dose of GSK2586184 and clinical response as assessed by the SRI following 12 weeks of treatment in SLE patients • To estimate the relationship between dose of GSK2586184 and clinical response as assessed by the SLEDAI-2K and S2K RI-50 scores following 12 weeks of treatment in SLE patients • To estimate the relationship between changes in the expression of selected mRNA transcripts following dosing with GSK2586184 and clinical response • To assess the pharmacokinetics of GSK2586184 in SLE patients. • To define the PK/PD relationship of JAK-1 inhibition on the interferon (IFN) transcriptional signature biomarker following 2 weeks of treatment. • To define the PK/PD relationship of JAK-1 inhibition on clinical response parameters following 12 weeks of treatment. • To estimate any impact of GSK2586184 treatment on patient reported outcomes ;Primary end point(s): 1. Interferon transcriptional signature biomarker expression over time (Interim Analysis 1, Primary Endpoint) 2. SELENA SLEDAI score over time (Interim Analysis 2, 3 and final analysis, Primary Endpoint) 3. Change from baseline for blood pressure, heart rate and temperature over time. 4. Change from baseline in clinical chemistry and hematology parameters over time. 5. Number and severity of adverse events during the study period.;Timepoint(s) of evaluation of this end point: * Primary endpoints 1 to 5 will be evaluated during the 12 week treatment period. * Primary endpoint 1 is the key	—

Measure

Time frame

Main Objective: • To estimate the relationship between dose of GSK2586184 and pharmacodynamic effect on expression of selected messenger ribonucleic acid (mRNA) transcripts following 2 weeks of treatment in SLE patients • To estimate the relationship between dose of GSK2586184 and clinical response as assessed by SELENA SLEDAI score following 12 weeks of treatment in SLE patients • To evaluate the safety and tolerability of repeat doses of GSK2586184 in SLE patients.;Secondary Objective: • To estimate the relationship between dose of GSK2586184 and clinical response as assessed by the SRI following 12 weeks of treatment in SLE patients • To estimate the relationship between dose of GSK2586184 and clinical response as assessed by the SLEDAI-2K and S2K RI-50 scores following 12 weeks of treatment in SLE patients • To estimate the relationship between changes in the expression of selected mRNA transcripts following dosing with GSK2586184 and clinical response • To assess the pharmacokinetics of GSK2586184 in SLE patients. • To define the PK/PD relationship of JAK-1 inhibition on the interferon (IFN) transcriptional signature biomarker following 2 weeks of treatment. • To define the PK/PD relationship of JAK-1 inhibition on clinical response parameters following 12 weeks of treatment. • To estimate any impact of GSK2586184 treatment on patient reported outcomes ;Primary end point(s): 1. Interferon transcriptional signature biomarker expression over time (Interim Analysis 1, Primary Endpoint) 2. SELENA SLEDAI score over time (Interim Analysis 2, 3 and final analysis, Primary Endpoint) 3. Change from baseline for blood pressure, heart rate and temperature over time. 4. Change from baseline in clinical chemistry and hematology parameters over time. 5. Number and severity of adverse events during the study period.;Timepoint(s) of evaluation of this end point: * Primary endpoints 1 to 5 will be evaluated during the 12 week treatment period. * Primary endpoint 1 is the key

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Secondary

Measure	Time frame
Secondary end point(s): 1. SRI Response Rate over time. Response is defined as: = 4 point reduction from baseline in the SELENA SLEDAI score, AND No worsening (increase of <0.30 points from baseline) in Physicians Global Assessment (PGA) AND No new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with baseline. To evaluate the response over time, the percentage of subjects achieving a response on the composite endpoint, and each of the components of this endpoint, will be presented by visit. 2. Change from baseline in SLEDAI-2K score and the S2K RI-50 score during 12 weeks of treatment with GSK2586184 3. Individual plasma concentrations of GSK2586184 and data permitting, summary PK parameters. 4. Mean change from baseline in Short Form-36 Health Survey (SF-36) score (8 domains) at Week 12. 5. Mean change from baseline in Brief Fatigue Inventory (BFI) score (9 items) at Weeks 2, 4, 6, 8, 10 and 12. 6. Mean change from baseline in Brief Pain Inventory (BPI) (short form) score (15 items) at weeks 2, 4, 6, 8, 10 and 12.;Timepoint(s) of evaluation of this end point: Secondary endpoints 1 through 6 will be evaluated during the 12 week treatment period.	—

Measure

Time frame

Secondary end point(s): 1. SRI Response Rate over time. Response is defined as: = 4 point reduction from baseline in the SELENA SLEDAI score, AND No worsening (increase of <0.30 points from baseline) in Physicians Global Assessment (PGA) AND No new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with baseline. To evaluate the response over time, the percentage of subjects achieving a response on the composite endpoint, and each of the components of this endpoint, will be presented by visit. 2. Change from baseline in SLEDAI-2K score and the S2K RI-50 score during 12 weeks of treatment with GSK2586184 3. Individual plasma concentrations of GSK2586184 and data permitting, summary PK parameters. 4. Mean change from baseline in Short Form-36 Health Survey (SF-36) score (8 domains) at Week 12. 5. Mean change from baseline in Brief Fatigue Inventory (BFI) score (9 items) at Weeks 2, 4, 6, 8, 10 and 12. 6. Mean change from baseline in Brief Pain Inventory (BPI) (short form) score (15 items) at weeks 2, 4, 6, 8, 10 and 12.;Timepoint(s) of evaluation of this end point: Secondary endpoints 1 through 6 will be evaluated during the 12 week treatment period.

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Countries

Argentina, Brazil, Chile, Czech Republic, Estonia, Germany, Greece, Hong Kong, Hungary, India, Korea, Republic of, Mexico, Peru, Poland, Russian Federation, South Africa, Spain, Sweden, Thailand

Contacts

Public ContactClinical Trials Helpdesk

GlaxoSmithKline

GSKClinicalSupportHD@gsk.com+44 02089904466

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026