A Dose Ranging Study to Evaluate the Safety and Efficacy of GSK2586184 in Patients With Chronic Plaque Psoriasis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01782664
First received: January 31, 2013
Last updated: June 19, 2014
Last verified: May 2014
  Purpose

A multi-centre, randomised, dose ranging study to evaluate the safety and clinical efficacy of GSK2586184 in patients with chronic plaque psoriasis.

There will be 2 study cohorts (Cohorts A and B). Cohort A is the main study cohort, and this part of the study will be randomised, double-blind and placebo-controlled. Fifty-six subjects will be randomised in Cohort A: 14 subjects in each treatment group: 100 mg, 200 mg or 400 mg GSK2586184, or placebo. Cohort B is an exploratory, open-label investigation of the effect of 400 mg GSK2586184 on inflammatory gene expression in the skin and whole blood, and GSK2586184 concentrations in the skin. A maximum of 8 subjects will be included, and all subjects will take 400 mg GSK2586184.

In both Cohorts A and B, study medication will be administered orally (as tablets), twice daily, for up to 12 weeks.

Each subject will have 7 out-patient visits: Screening; Baseline & Start of treatment; Week 2; Week 4; Week 8; Week 12; and Follow-up (Week 16)


Condition Intervention Phase
Psoriasis
Drug: 100 mg GSK2586184
Drug: 200 mg GSK2586184
Drug: 400 mg GSK2586184
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-centre, Randomised, Double-blind, Placebo-controlled, Dose Ranging Study to Evaluate the Safety and Efficacy of GSK2586184 in Patients With Chronic Plaque Psoriasis

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • The proportion of subjects who achieve >=75% improvement from baseline in PASI score at Week 12 (PASI 75) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The Psoriasis Area Severity Index (PASI) assessment will be performed by the investigator or a suitably trained delegate. The lesions on each area of the body will be assessed for redness, thickness, and scaling.


Secondary Outcome Measures:
  • Safety and tolerability of twice-daily doses of GSK2586184 [ Time Frame: Up to Week 16 ] [ Designated as safety issue: No ]
    To be assessed by adverse event reporting, laboratory safety data, vital signs, and 12-lead ECG monitoring.

  • Change from baseline and actual PASI scores at Weeks 2, 4, 8 and 12 [ Time Frame: Baseline and Weeks 2, 4, 8 and 12. ] [ Designated as safety issue: No ]
    See above for description of PASI scoring.

  • The proportion of subjects who achieve >=50% and >=90% improvement from baseline in PASI score at Weeks 2, 4, 8 and 12 (PASI 50 and PASI 90) [ Time Frame: Baseline and Weeks 2, 4, 8 and 12. ] [ Designated as safety issue: No ]
    See above for description of PASI scoring.

  • The proportion of subjects who achieve >=75% improvement from baseline in PASI score at Weeks 2, 4 and 8 (PASI 75). [ Time Frame: Baseline and Weeks 2, 4 and 8. ] [ Designated as safety issue: No ]
    See above for description of PASI scoring.

  • Time to PASI 75. [ Time Frame: Up to Week 16 ] [ Designated as safety issue: No ]
    See above for description of PASI scoring.

  • The proportion of subjects in each PGA score category at Weeks 2, 4, 8 and 12 [ Time Frame: Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    The Physician Global Assessment (PGA) will be performed by the investigator or a suitably trained delegate. It is a global lesion score, and subjects will be scored using the following categories: 0 = Clear, 1 = Almost clear, 2 = Mild, 3 = Mild to moderate, 4 = Moderate, 5 = Moderate to severe, 6 = Severe.

  • The proportion of subjects who have a PGA score of 'clear' (0) or 'almost clear' (1) at Weeks 2, 4, 8 and 12. [ Time Frame: Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    See above for description of PGA scoring.

  • Time to PGA score of 'clear' (0) or 'almost clear' (1) [ Time Frame: Up to Week 16 ] [ Designated as safety issue: No ]
    See above for description of PGA scoring.

  • Change from baseline and actual VAS itch score [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    A visual analogue scale will be used to assess any change in itch.

  • Change from baseline of Dermatology Life Quality Index (DLQI) score [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The DLQI is a validated questionnaire, which will be used to assess any change in quality of life.

  • Plasma concentrations and derived pharmacokinetic parameters of GSK2586184 [ Time Frame: Baseline (pre-dose), Week 2 (pre-dose, 23 h, 34 h post-dose), Week 4 (46 h, 68 h post-dose), Week 8 and Week 12 ] [ Designated as safety issue: No ]
    Pharmacokinetic (PK) parameters will be calculated following repeat doses of GSK2586184, including area under the concentration-time curve over the dosing interval (AUC(0-tau)), apparent clearance (CL/F), apparent volume of distribution (V/F) and maximum plasma concentration (Cmax).

  • Change from baseline of neopterin concentrations [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    Blood samples will be taken to measure serum neopterin concentrations


Enrollment: 68
Study Start Date: March 2013
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 100 mg GSK2586184
Subjects will be randomized to 100 mg GSK2586184 twice daily for up to 84 days
Drug: 100 mg GSK2586184
100 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.
Experimental: 200 mg GSK2586184
Subjects will be randomized to 200 mg GSK2586184 twice daily for up to 84 days
Drug: 200 mg GSK2586184
200 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.
Experimental: 400 mg GSK2586184
Subjects will be randomized to 400 mg GSK2586184 twice daily for up to 84 days
Drug: 400 mg GSK2586184
400 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.
Placebo Comparator: Placebo
Subjects will be randomized to receive Placebo twice daily for up to 84 days
Drug: Placebo
Placebo tablets to be taken twice daily with food for up to 84 days.
Experimental: 400 mg GSK2586184 (Cohort B)
Subjects will take 400 mg GSK2586184 twice daily for up to 84 days
Drug: 400 mg GSK2586184
400 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Otherwise healthy subjects with a diagnosis of moderate to severe plaque psoriasis defined by the following criteria:
  • Diagnosed for at least 12 months before the first dose of study medication
  • Psoriasis plaques cover >=10% of body surface area.
  • PASI score of >=12, and PGA score of>=3, and suitable for systemic or light therapy.
  • Male or female, between 18 and 75 years of age inclusive.
  • Female subjects of childbearing potential must agree to avoid pregnancy and male subjects must agree to avoid female partners becoming pregnant.
  • Subjects must agree to use ultra violet (UV) light protection.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

  • Unable to refrain from the use of the following prescription and non-prescription drugs from the following periods before the first dose of study medication until completion of the follow-up visit:
  • 12 weeks: alefacept, ustekinumab, adalimumab, etanercept, infliximab, or certolizumab pegol
  • 4 weeks or 5 half-lives, whichever is longer:
  • systemic medications for other medical conditions that are known to affect psoriasis, including but not limited to oral corticosteroids, cyclosporine, methotrexate, lithium, and beta-adrenergic blockers
  • 7 days or 5 half-lives, whichever is longer:
  • statins and other OATP and BCRP sensitive substrates (e.g. rapaglinide)
  • any agent known to be a substrate of MATE1 and MATE2-K, which undergoes significant renal secretion (e.g. cimetidine)
  • 3 weeks or 5 half-lives, whichever is longer:
  • any agent known to be a strong CYP3A4 inhibitor or inducer
  • 2 weeks: topical therapies that are known to affect psoriasis, including but not limited to corticosteroids, retinoids, vitamin D derivatives, tar and anthralin
  • Other medications (including vitamins, herbal and dietary supplements) will be considered on a case-by-case basis, and will be allowed if in the opinion of the investigator the medication will not interfere with the study procedures or compromise subject safety.
  • Phototherapy within 4 weeks before the first dose of study medication.
  • A live vaccination within 4 weeks before the first dose of study medication, or a live vaccination planned during the course of the study (until completion of the follow-up visit).
  • A major organ transplant (e.g. heart, lung, kidney, liver) or haematopoietic stem cell/marrow transplant.
  • Significant unstable or uncontrolled acute or chronic disease unrelated to psoriasis (i.e. cardiovascular including uncontrolled hypertension, hypercholesterolemia, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases) which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.
  • A planned surgical procedure that, in the opinion of the investigator, makes the subject unsuitable for the study.
  • 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.
  • Acute or chronic infections, as follows:
  • Known previous or active infection with Mycobacterium Tuberculosis
  • Currently on any suppressive therapy for a chronic infection (such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria).
  • Hospitalisation for treatment of infection within 60 days before first dose.
  • Use of parenteral (IV or intramuscular) antibiotics (antibacterials, antivirals, antifungals, or antiparasitic agents) within 60 days before first dose.
  • Unable to refrain from the consumption of grapefruit or grapefruit juice from 3 weeks before the first dose of study medication until 2 weeks after the last dose of study medication.
  • History of sensitivity to any components of the study medications, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates their participation.
  • Serologic evidence of Hepatitis B (HB) infection based on the results of testing for HBsAg, anti-HBc antibody as follows: subjects positive for HBsAg are excluded; and subjects positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded.
  • Positive test for Hepatitis C antibody confirmed sample with a Hepatitis C RIBA immunoblot assay or equivalent. Subjects who are positive for Hepatitis C antibody, but negative when the Hepatitis C RIBA immunoblot assay or equivalent test is performed will be eligible to participate. Subjects who are positive for Hepatitis C antibody and have a positive or indeterminate result when the Hepatitis C RIBA immunoblot assay or equivalent test is performed will not be eligible to participate.
  • A positive test for HIV antibody.
  • Pregnant females as determined by a positive serum hCG test at screening, or a positive urine hCG test pre-dose on Day 1.
  • Lactating females.
  • Haemoglobin <11 g/dL, haematocrit <30%, WBC count (absolute) <3 × 10^9/L, neutrophils <1.5 × 10^9/L, platelets <100 × 10^9/L, lymphocytes <1 x 10^9/L.
  • Current or history of renal disease, or estimated creatinine clearance <60 mL/min/1.73m^2 or serum creatinine >1.5 ULN.
  • Single QTc > 450 msec; or QTc > 480 msec in subjects with Bundle Branch Block.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • ALT > 2xULN; alkaline phosphatase and bilirubin ≥ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
  • The subject has participated in a clinical trial and has received an investigational product within 3 months before the first dose of study medication, or plans to take part in another clinical trial at the same time as participating in this clinical trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01782664

Locations
Germany
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70178
GSK Investigational Site
Augsburg, Bayern, Germany, 86179
GSK Investigational Site
Osnabrueck, Niedersachsen, Germany, 49074
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48159
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48149
GSK Investigational Site
Witten, Nordrhein-Westfalen, Germany, 58453
GSK Investigational Site
Berlin, Germany, 13507
GSK Investigational Site
Berlin, Germany, 10117
GSK Investigational Site
Berlin, Germany, 10827
GSK Investigational Site
Hamburg, Germany, 20354
United Kingdom
GSK Investigational Site
Cardiff, United Kingdom, CF14 4XN
GSK Investigational Site
London, United Kingdom, SE1 7EH
GSK Investigational Site
London, United Kingdom, NW3 2QG
GSK Investigational Site
Salford, United Kingdom, M6 8HD
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01782664     History of Changes
Other Study ID Numbers: 116679
Study First Received: January 31, 2013
Last Updated: June 19, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte

Keywords provided by GlaxoSmithKline:
PASI
DLQI
GSK2586184
plaque-type psoriasis
PGA
inflammatory gene transcription
JAK-1 inhibitor
serum neopterin
skin biopsy
ACR response criteria
VAS itch score

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases

ClinicalTrials.gov processed this record on August 27, 2014