A Multicentre, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of GSK2982772 in Participants With Moderate to Severe Plaque Psoriasis
Overview
- Phase
- Phase 1
- Intervention
- GSK2982772
- Conditions
- Psoriasis
- Sponsor
- GlaxoSmithKline
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- Percentage (%) of Participants Who Achieved Greater Than or Equal (>=) to 75% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
Plaque psoriasis is a chronic relapsing inflammatory skin disease that is characterized by keratinocyte hyper-proliferation and epidermal hyperplasia. Standard treatment for psoriasis generally requires long-term use of topical therapies, psoralen and ultraviolet A (PUVA), ultraviolet B (UVB) and/or systemic immunosuppressant therapies to achieve and maintain adequate disease control. This is a multicenter, randomized, double-blind study conducted in participants with moderate to severe plaque psoriasis. The study will evaluate the efficacy, safety, pharmacokinetic and pharmacodynamics profile of 960 milligram (mg) GSK2982772 administered as a once daily modified release (MR) formulation. Participants will be randomized in a 2:1 ratio to receive either 960 mg GSK2982772 or placebo for 12 weeks. The duration of the study, including Screening and follow-up, will be approximately 21 weeks for each participant.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants between 18 and 75 years of age inclusive, at the time of signing the informed consent.
- •Diagnosis of plaque psoriasis for at least 6 months before Screening visit.
- •Evidence of moderate to severe psoriasis, at Screening and Baseline before the first dose of study treatment, with: PASI score \>=12; Psoriasis plaques involving BSA \>=10 percent and sIGA\>=
- •Candidate for systemic therapy or phototherapy (includes naïve or previously treated), in the opinion of the Investigator.
- •Agrees to avoid any prolonged exposure to natural or artificial sources of ultraviolet (UV) radiation from 28 days before Day 1 until the follow-up visit, which may potentially impact the participant's psoriasis in the opinion of the Investigator.
- •Body mass index (BMI) within the range of 18.5 to 40.0 kilogram (kg)/meter square (m\^2).
- •Preclinical data has not identified risk of clinically relevant genotoxicity, however there is demonstrated/suspected risk of teratogenicity/fetotoxicity. Accordingly, the following contraceptive advice must be adhered to for male and female participants.
- •Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Male participants are eligible to participate if they agree to the following during the intervention period and for at least 2 days (i.e. 5 terminal half-lives of GSK2982772) after the last dose of study intervention: Refrain from donating sperm plus either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed: Agree to use a male condom and will also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a WOCBP OR Is a WOCBP and using a contraceptive method that is highly effective preferably with low user dependency, during the intervention period and for at least 28 days (i.e. until resolution of potential drug interaction with combined hormonal contraceptives) after the last dose of study intervention. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (example an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Exclusion Criteria
- •Non-plaque forms of psoriasis (example erythrodermic, guttate, or pustular), in the opinion of the Investigator.
- •Drug-induced psoriasis (example a new onset of psoriasis or an exacerbation from beta blockers, calcium channel blockers, lithium or anti-Tumor-Necrosis Factor \[TNF\] therapies).
- •Diagnosis of psoriatic arthritis, uveitis, inflammatory bowel disease, or other immune-mediated conditions that are commonly associated with psoriasis for which a participant requires current systemic (oral, subcutaneous \[SC\], or intravenous \[IV\]) (including corticosteroids and biologics) immunosuppressant medical treatment.
- •Current Suicidal Ideation Behavior (SIB) as measured using the Columbia Suicide Severity Rating Scale (C-SSRS) or a history of attempted suicide at Screening and before first dose of study treatment.
- •Active infection, or a history of infections as follows: Hospitalization for treatment of infection within 60 days before Day 1; Current use of any suppressive therapy for a chronic infection (such as pneumocystis jirovecii, cytomegalovirus, herpes simplex virus, herpes zoster virus and atypical mycobacteria); Use of parenteral (IV or intramuscular) antibiotics (anti-bacterials, antivirals, antifungals, or anti-parasitic agents) within 60 days before Day 1; History of opportunistic infections within 1 year of Screening (example pneumocystis jirovecii, Cytomegalovirus \[CMV\] pneumonitis, aspergillosis). This does not include infections that may occur in immunocompetent individuals, such as fungal nail infections or vaginal candidiasis, unless it is of an unusual severity or recurrent nature; History of recurrent, chronic or other active infection that in the opinion of the Investigator may put the participant at unacceptable risk or interfere/confound the integrity of study data; Positive test for Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) at screening or interaction with known Coronovirus Disease 2019 (COVID19) positive contacts within 14 days prior to Day 1; History of latent or active Tuberculosis (TB), irrespective of treatment status; A positive diagnostic TB test at Screening defined as a positive QuantiFERON-TB Gold plus test.
- •Current or history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •Current or history of renal disease.
- •Significant unstable or uncontrolled cardiovascular disease including uncontrolled hypertension.
- •Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.
- •History of major organ transplant (example heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
Arms & Interventions
Participants receiving GSK2982772 960 mg
Participants will receive GSK2982772 960 mg oral tablets once daily for 12 weeks.
Intervention: GSK2982772
Participants receiving placebo
Participants will receive GSK2982772 matching placebo oral tablets once daily for 12 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Percentage (%) of Participants Who Achieved Greater Than or Equal (>=) to 75% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12
Time Frame: Baseline and Week 12
The Psoriasis area severity index (PASI) is a standard tool for assessing the severity of psoriasis that considers the overall severity of erythema, induration, and scaling (each scored separately), and the extent of body surface area (BSA) affected with psoriasis. The 3 clinical signs are each graded on a 5-point scale (0=none to 4=severe) and the percent BSA affected is scored on a 7-point scale (0= 0% skin with psoriasis to 6= ≥ 90% skin with psoriasis). The individual scores are multiplied by a weighted factor for each body region; the sum of these scores gives the overall PASI score. The PASI is a composite scoring assessed by the investigator for the severity of lesions and the area affected into a single score with a range of 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Note: The 95% credible interval (CrI) was reported as a method of dispersion.
Secondary Outcomes
- Percentage of Participants Who Achieved >=50% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12(Baseline and Week 12)
- Percentage of Participants Who Achieved >=90% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12(Baseline and Week 12)
- Percentage of Participants Who Achieved >=100% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12(Baseline and Week 12)
- Percentage of Participants Who Have a Static Investigator's Global Assessment (sIGA) Score of 0 or 1 at Week 12(At Week 12)
- Number of Participants With Any Adverse Events (AEs)(Up to Day 120)
- Number of Participants With Drug Related AEs(Up to Day 120)
- Change From Baseline in Psoriasis Area Severity Index (PASI) Scores at Week 12(Baseline and Week 12)
- Change From Baseline in Psoriatic Body Surface Area (BSA) at Week 12(Baseline and Week 12)
- Number of Participants With Common (Occurring at Least 5%) Non Serious AEs(Up to Day 120)
- Number of Participants With AEs Leading to Permanent Discontinuation of Study Intervention(Up to Day 120)
- Number of Participants With SAEs Including Any SAEs, SAEs Related to Study Intervention, and Fatal SAEs(Up to Day 120)