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

NCT01782664 | Completed Phase 2 Results

• 1 other identifier: 116679
• Study Type: interventional
• Target: 68
• Locations: 2 countries
• Sites: 15

Brief Summary

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)

Conditions

Psoriasis

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Had Achieved >=75% Improvement From Baseline in the Psoriasis Area Severity Index (PASI) Score at Week 12 (PASI 75)

  PASI score was determined by evaluation of body surface area (BSA) covered by plaque psoriasis in 4 areas (head/neck, arms, trunk and legs with area score of 0.1, 0.2, 0.3 and 0.4 respectively). This test included combination of both degree of involvement (assessed as per the % of affected body area using a 7-point scale such that 0=0% involvement, 1=1-9%, 2=10-29%, 3=30-49%, 4=50-69%, 5=70-89% and 6=90-100%) and severity (evaluated individually using a 5-point scale that ranged as 0=No evidence of sign, 1=slight evidence, 2=moderate evidence, 3=marked evidence and 4=very marked, most severe evidence of sign) of erythema, induration and desquamation in each of the same 4 areas. PASI score ranges from 0(no psoriasis) to 72(worse psoriasis). Final PASI=(sum of severity score for each area)x(% body affected score x area score). Baseline=Day 1. Percentage of participants who achieved \>= 75% improvement from Baseline was reported with last observation carried forward (LOCF) analysis.

  Baseline and Week 12

• Percentage of Participants Who Had Achieved >=75% Improvement From Baseline in the Psoriasis Area Severity Index (PASI) Score at Week 12 (PASI 75)

  PASI score was determined by evaluation of BSA covered by plaque psoriasis in 4 areas (head/neck, arms, trunk and legs with area score of 0.1, 0.2, 0.3 and 0.4 respectively). This test included combination of both degree of involvement (assessed as per the % of affected body area using a 7-point scale such that 0=0% involvement, 1=1-9%, 2=10-29%, 3=30-49%, 4=50-69%, 5=70-89% and 6=90-100%) and severity (evaluated individually using a 5-point scale that ranged as 0=No evidence of sign, 1=slight evidence, 2=moderate evidence, 3=marked evidence and 4=very marked, most severe evidence of sign) of erythema, induration and desquamation in each of the same 4 areas. PASI score ranges from 0(no psoriasis) to 72(worse psoriasis). Final PASI=(sum of severity score for each area)x(% body affected score x area score). Baseline=Day 1. Percentage of participants who achieved \>= 75% improvement from Baseline was reported with LOCF analysis.

  Baseline and Week 12

Secondary Outcomes (21)

• Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

  From Baseline (Day 1) until the Follow-up visit (Day 112)

• Number of Participants With the Indicated Hematology Parameters Falling Outside of the Reference Range at Any Time Post-Baseline (BL) During Study

  From BL (Day 1) until the Follow-up visit (Day 112)

• Number of Participants With the Indicated Clinical Chemistry Parameters Falling Outside the Reference Range at Any Time Post-Baseline (BL) During the Study

  From Baseline (Day 1) until the Follow-up visit (Day 112)

• Number of Participants With the Systolic (S) and Diastolic (D) Blood Pressure (BP) Falling Outside the Clinical Concern Range at Any Time Post-baseline During the Study

  From Baseline (Day 1) until the follow-up visit (Day 112)

• Number of Participants With the Heart Rate Falling Outside the Clinical Concern Range at Any Time Post-Baseline (BL) During the Study

  From Baseline (Day 1) until the Follow-up visit (Day 112)

Study Arms (5)

100 mg GSK2586184

EXPERIMENTAL

Subjects will be randomized to 100 mg GSK2586184 twice daily for up to 84 days

Drug: 100 mg GSK2586184

200 mg GSK2586184

EXPERIMENTAL

Subjects will be randomized to 200 mg GSK2586184 twice daily for up to 84 days

Drug: 200 mg GSK2586184

400 mg GSK2586184

EXPERIMENTAL

Subjects will be randomized to 400 mg GSK2586184 twice daily for up to 84 days

Drug: 400 mg GSK2586184

Placebo

PLACEBO COMPARATOR

Subjects will be randomized to receive Placebo twice daily for up to 84 days

Drug: Placebo

400 mg GSK2586184 (Cohort B)

EXPERIMENTAL

Subjects will take 400 mg GSK2586184 twice daily for up to 84 days

Drug: 400 mg GSK2586184

Interventions

100 mg GSK2586184 DRUG

100 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.

100 mg GSK2586184

200 mg GSK2586184 DRUG

200 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.

200 mg GSK2586184

400 mg GSK2586184 DRUG

400 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.

400 mg GSK2586184; 400 mg GSK2586184 (Cohort B)

Placebo DRUG

Placebo tablets to be taken twice daily with food for up to 84 days.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• weeks: alefacept, ustekinumab, adalimumab, etanercept, infliximab, or certolizumab pegol
• 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
• 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)
• weeks or 5 half-lives, whichever is longer:
• any agent known to be a strong CYP3A4 inhibitor or inducer
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (15)

GSK Investigational Site

Stuttgart, Baden-Wurttemberg, 70178, Germany

Location

GSK Investigational Site

Augsburg, Bavaria, 86179, Germany

Location

GSK Investigational Site

Osnabrück, Lower Saxony, 49074, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

GSK Investigational Site

Münster, North Rhine-Westphalia, 48149, Germany

Location

GSK Investigational Site

Münster, North Rhine-Westphalia, 48159, Germany

Location

GSK Investigational Site

Witten, North Rhine-Westphalia, 58453, Germany

Location

GSK Investigational Site

Berlin, 10117, Germany

Location

GSK Investigational Site

Berlin, 10827, Germany

Location

GSK Investigational Site

Berlin, 13507, Germany

Location

GSK Investigational Site

Hamburg, 20354, Germany

Location

GSK Investigational Site

Cardiff, CF14 4XN, United Kingdom

Location

GSK Investigational Site

London, NW3 2QG, United Kingdom

Location

GSK Investigational Site

London, SE1 7EH, United Kingdom

Location

GSK Investigational Site

Salford, M6 8HD, United Kingdom

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Psoriasis

Interventions

GSK2586184

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 31, 2013
• First Posted: February 4, 2013
• Study Start: March 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 24, 2014
• Last Updated: August 3, 2017
• Results First Posted: August 3, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will share

Locations

GB (4); DE (11)