Last updated: 11/07/2018 09:58:14
An adaptive Phase II study to evaluate the efficacy, pharmacodynamics, safety and tolerability of GSK2586184
EudraCT ID
EU CT Number
Not applicable
Trial status
Terminated (halted prematurely)
Terminated (halted prematurely)
Trial overview
Official title: An adaptive Phase II study to evaluate the efficacy, pharmacodynamics, safety and tolerability of GSK2586184 in patients with mild to moderate systemic lupus erythematosus
Trial description: This is an adaptive, dose ranging, Phase II study to investigate the relationship between repeat doses of GSK2586184 and the pharmacodynamic effect and clinical efficacy in patients with active systemic lupus erythematosus (SLE). This study will also investigate the safety and tolerability of repeat doses of GSK2586184. During the study, up to 3 Interim Analyses will be conducted. These are to monitor the pharmacodynamic effect and safety following 2 weeks of therapy (Interim Analysis 1); and the clinical efficacy and safety of GSK2586184 following 12 weeks of therapy (Interim Analyses 2 and 3). Subjects who meet the entry criteria (approximately 150 to 250) will be randomized in a 1:1:1:1:1 ratio to receive GSK2586184 at doses of 50 milligram (mg) twice daily (b.i.d), 100 mg b.i.d, 200 mg b.i.d, 400 mg b.i.d or Placebo b.i.d. GSK2586184 tablets available in 50 and 200 mg dose strength will be administered orally up to 12 weeks.Subjects who complete the study will participate in the study for approximately 21 weeks.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Percentage Inhibition from Baseline of interferon (IFN) Transcriptional Biomarkers at Week 2
Timeframe: Baseline(Day1) and Week 2
Change from Baseline of SELENA SLEDAI score at indicated time points up to Week 16
Timeframe: Baseline(Day1), Weeks 2, 4, 6, 8, 10, 12 and 16
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the indicated time points up to Week 16
Timeframe: Baseline (Day1), Weeks 2, 4, 6, 8, 10, 12 and 16
Change from Baseline in heart rate at the indicated time points up to Week 16
Timeframe: Baseline (Day 1), Weeks 2, 4, 6, 8, 10, 12 and 16
Change from Baseline in temperature at the indicated time points up to Week 16
Timeframe: Baseline (Day 1), Weeks 2, 4, 6, 8, 10, 12 and 16
Change from Baseline in albumin, globulin and protein at the indicated time points up to Week 16
Timeframe: Baseline (Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from baseline in alkaline phosphatase(ALP), alanine amino transferase(ALT), aspartate amino transferase(AST), creatine kinase (CK), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) at the indicated time points up to Week 16
Timeframe: Baseline (Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in anion gap, calcium, cholesterol, chloride, carbon dioxide, glucose, HDL cholesterol, potassium, LDL cholesterol, magnesium, phosphate, soidium, triglycerides, urea, VLDL cholesterol at the indicated time points up to Week 16
Timeframe: Baseline (Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in bilirubin, creatinine, iron binding capacity, iron and urate at the indicated time points up to Week 16
Timeframe: Baseline (Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in albumin/globulin, BUN/creatinine and transferrin saturation at the indicated time points up to Week 16
Timeframe: Baseline(Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in creatinine clearance at the indicated time points up to Week 16
Timeframe: Baseline (Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils, neutrophils segmented (SG), platelets and leukocytes at the indicated time points up to Week 16
Timeframe: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, neutrophils/leukocytes, neutrophils SG/leukocytes and erythrocyte distribution width (EDW) at the indicated time points up to Week 16
Timeframe: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in erythrocytes and reticulocytes at the indicated time points up to Week 16
Timeframe: Baseline (Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in hemoglobin and erythrocyte mean corpuscular hemoglobin concentration (EMCHC) at the indicated time points up to Week 16
Timeframe: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in erythrocyte mean corpuscular hemoglobin (EMCH) at the indicated time points up to Week 16
Timeframe: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in erythrocyte mean corpuscular volume (EMCV) and mean platelet volume (MPV) at the indicated time points up to Week 16
Timeframe: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in hematocrit and reticulocytes/erythrocytes at the indicated time points up to Week 16
Timeframe: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
Number of participants with urinalysis data at the indicated time points up to Week 16
Timeframe: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in urine protein at the indicated time points up to Week 16
Timeframe: Baseline(Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
Change from Baseline in urine protein/creatinine at the indicated time points up to Week 16
Timeframe: Baseline(Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
Number of participants with any adverse events (AEs) and any serious adverse events (SAEs) up to Week 16
Timeframe: Up to Week 16
Number of participants with severity Grade 1, 2, 3, 4 and 5 adverse events (AEs)
Timeframe: Up to 16 Weeks
Secondary outcomes:
SRI Response Rate at Week 4, 8, 12 and 16
Timeframe: Week 4, 8, 12 and 16
Change from baseline in SLEDAI-2K score and the S2K RI-50 score over time (up to Week 12)
Timeframe: Baseline(Day 1) to Week 12
Mean GSK2586184 plasma concentrations on Weeks 2, 4, 6, 8, 10 and 12
Timeframe: Weeks 2, 4, 6, 8, 10 and 12
Area under the concentration-time curve over the dosing interval (AUC[0-tau]) up to Week 12
Timeframe: Weeks 2, 4, 6, 8, 10 and 12
Apparent clearance (CL/F) up to Week 12
Timeframe: Weeks 2, 4, 6, 8, 10 and 12
Volume of distribution (Vss) up to Week 12
Timeframe: Weeks 2, 4, 6, 8, 10 and 12
Mean change from Baseline in the SF-36 Domain Scores up to Week 16
Timeframe: Baseline(Day 1), Weeks 12 and 16
Mean change from Baseline in the Brief Fatigue Inventory (BFI) Domain Score up to Week 16
Timeframe: Baseline (Day 1), Weeks 2, 4, 6, 8, 10, 12 and 16
Mean change from Baseline in the Brief Pain Inventory (BPI) Domain Score up to Week 16
Timeframe: Baseline(Day 1), Weeks 2, 4, 6, 8, 10, 12 and 16
Interventions:
Drug: GSK2586184 50 mg
Drug: GSK2586184 100 mg
Drug: GSK2586184 200 mg
Drug: GSK2586184 400 mg
Drug: Placebo
Enrollment:
51
Observational study model:
Not applicable
Primary completion date:
2014-31-03
Time perspective:
Not applicable
Clinical publications:
Lesley Kahl, Jatin Patel, Mark Layton, Michael Binks, Kirsty Hicks, Gustavo Leon, Eric Hachulla, Daniel Machado, Delphine Staumont-Salle, Marion Dickson, Lynn Condreay, Lorrie Schifano, Stefano Zamuner, and Ronald van Vollenhoven on behalf of the JAK115919 Study Team. Safety, tolerability, efficacy and pharmacodynamics of the selective JAK1 inhibitor GSK2586184 in patients with systemic lupus erythematosus. Lupus. 2016;25(13):1420-1430.
Medical condition
Systemic Lupus Erythematosus
Product
solcitinib
Collaborators
Not applicable
Study date(s)
March 2013 to March 2014
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 75 years
Accepts healthy volunteers
No
- Age & Gender: Male or female between 18 and 75 years of age inclusive
- SLE classification: a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria
- Kidney Disease: meeting any of the following criteria:
- Proteinuria > 0.5g/24 hour OR equivalent spot urine protein to creatinine ratio of 0.5mg/mg; Serum creatinine > 1.5 X upper limit of normal (ULN); active nephritis requiring acute therapy not permitted by protocol; required peritoneal dialysis or hemodialysis or high dose corticosteroid (> 100 mg/day prednisone or equivalent) within 90 days prior to first dose; active renal disease shown on renal biopsy in the three months prior to screening.
Inclusion and exclusion criteria
Inclusion criteria:
- Age & Gender: Male or female between 18 and 75 years of age inclusive
- SLE classification: a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria
- Severity of disease: clinically active SLE disease defined as a SELENA SLEDAI score ≥8 at screening
- Auto antibodies: serologically active having unequivocally positive anti-nuclear antibody (ANA) or anti-double stranded DNA (anti-dsDNA) antibody test results from 2 independent time points
- Treatment for SLE: patient stable on either no treatment or a stable dose of: corticosteroids (<=15 mg/day prednisolone or equivalent) and /or hydroxychloroquine (<=400 mg daily dose) Subjects receiving azathioprine (<=2 mg/kg/day or <=150 mg/day, whichever is greater) or mycophenolate mofetil (<=1.5 g/day), or methotrexate (MTX) (<=20 mg/week), either alone or in addition to steroids and / or hydroxychloroquine
- Prevention of Pregnancy: A female Subject is eligible to participate if she is not pregnant or nursing; is of non-childbearing potential. Females of child-bearing potential must agree to use one highly effective contraception method in addition to barrier protection OR two forms of highly effective contraception.
- Informed consent: Capable of giving written informed consent
Exclusion criteria:
- Kidney Disease: meeting any of the following criteria: Proteinuria > 0.5g/24 hour OR equivalent spot urine protein to creatinine ratio of 0.5mg/mg; Serum creatinine > 1.5 X upper limit of normal (ULN); active nephritis requiring acute therapy not permitted by protocol; required peritoneal dialysis or hemodialysis or high dose corticosteroid (> 100 mg/day prednisone or equivalent) within 90 days prior to first dose; active renal disease shown on renal biopsy in the three months prior to screening.
- CNS Disease: active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS vasculitis) requiring therapeutic intervention within 60 days prior to first dose.
- Alcohol Abuse: Evidence or, in the opinion of the investigator, suspicion of alcohol consumption exceeding national guidelines and / or symptoms of alcohol dependency.
- Substance abuse: evidence of current recreational drug abuse or dependence.
- Hepatitis B: A positive pre-study Hepatitis B surface antigen or anti-Hepatitis B core antibody test at screening
- Hepatitis C: A positive Hepatitis C antibody at screening.
- HIV: A positive test for HIV antibody
- Previous Investigational Product Exposure: The subject has participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) prior to the first dosing day in the current study; OR exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Previous and current medication: Use of prescription or non-prescription drugs, including: agents known to interact with GSK2586184, erythopoetic stimulation factors; vitamins, herbal and dietary supplements
- Prior biological therapies: treatment with a biological therapy within the last 12 months
- Transplantation: Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
- Uncontrolled Other Diseases: Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.
- Surgery and Other Conditions: Have a planned surgical procedure or a history of any other medical disease laboratory abnormality, or condition that, in the opinion of the investigator, makes the subject unsuitable for the study.
- Cancer: Have a history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.-
- Infections: have required management of acute or chronic infections as follows: currently on any suppressive therapy for a chronic infection (such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria); OR hospitalisation for treatment of infection OR use of parenteral (IV or intramuscular) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 60 days prior to first dose.
- Mycobacterium Tuberculosis: Known latent or active infection with Mycobacterium Tuberculosis. Screening procedures consistent with local guidelines should be implemented.
- Haematology: neutrophil count <=1.5 X 10^9/L, Hb <=10g/dL, lymphocyte count <=350/mm^3 or 0.35 x 10^9/L and platelet count <=100 X 10^9/L
- Serum immunoglobulin (Ig) levels: IgG and/or IgM <= the lower limit of normal (LLN)
- Liver function tests: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >=2x upper limit of normal (ULN); alkaline phosphatase and bilirubin >1.5xULN (isolated bilirubin >1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Other laboratory abnormalities: Any Grade 3 or 4 haematology or clinical chemistry laboratory abnormality
- Drug sensitivity: History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Blood donation: Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
Trial location(s)
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50937
Status
Study Complete
Location
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ciudad de Buenos Aires, Buenos Aires, Argentina, C1431FWO
Status
Study Complete
Location
GSK Investigational Site
Pinelands, Cape Town, South Africa, 7405
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Juan, San Juan, Argentina, J5402DIL
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Jena, Thueringen, Germany, 07747
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
Status
Study Complete
Location
GSK Investigational Site
Stellenbosch, South Africa, 7600
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Herne, Nordrhein-Westfalen, Germany, 44652
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Kiel, Schleswig-Holstein, Germany, 24105
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Terminated (halted prematurely)
Actual primary completion date
2014-31-03
Actual study completion date
2014-31-03
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
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