Clinical trial NCT04316585: A Study to Evaluate the Benefit and Safety of GSK2982772 in Moderate to Severe Psoriasis Participants
Official title: A Multicentre, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of GSK2982772 in Participants With Moderate to Severe Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psoriasis
Keywords: Plaque Psoriasis
Modified Release
GSK2982772
Skin Biopsy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2020-03-20
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will randomized in ratio of 2:1 to receive either 960 mg GSK2982772 or placebo
Primary purpose: TREATMENT

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.


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\>=3.
* 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.
* The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.

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.
* Planned surgical procedure that makes the participant unsuitable for the study, in the opinion of the Investigator.
* History of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell carcinoma) or carcinoma in situ of the uterine cervix that has been fully treated and shows no evidence of recurrence after at least 12 months following treatment.
* History of significant progressive neurologic disorders including, but not limited to, progressive Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Alzheimer's and dementia.
* History of a medical condition other than plaque psoriasis, or other considerations, which may confound interpretation of efficacy or safety study data, or put the participant at unacceptable risk, in the opinion of the Investigator.
* History of lack of primary response to anti-TNF biologic therapies (either approved or experimental) at approved doses (or at the doses received if experimental therapies) after at least 3 months of therapy.
* Participant has previous exposure to 3 or more biologic therapies of any mechanism of action.
* Treatment with the prohibited therapies or changes to those treatments, within the specified timeframe. Other medications (including vitamins, herbal and dietary supplements) will be considered on a case-by-case basis and will be allowed if the medication will not interfere with the study procedures or compromise participant safety, in the opinion of the Investigator.
* Participation in a clinical trial and has received an investigational product within 30 days or 5 half-lives whichever is longer (or 12 weeks for biologic therapies), 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.
* Exposure to more than four investigational products within 12 months prior to the first dosing day.
* Average QT Duration Corrected for Heart Rate (QTc) \>450 milliseconds (msec) or QTc\>480 msec in participants with bundle branch block at Screening and before first dose of study treatment. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF). It is either machine-read or manually over-read.
* Alanine transferase (ALT) \>2 × upper limit of normal (ULN)
* Bilirubin \>1.5 × ULN at Screening (isolated bilirubin \>1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent).
* Estimated glomerular filtration rate (GFR) by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) \<60 milliliter (mL)/minute (min)/1.73 m\^2.
* Hemoglobin \< 10 gram per deciliter (g/dL); hematocrit \< 30 percent, white blood cell count \<= 3000 /cubic millimeter (mm\^3) (\<= 3.0 x 10\^9/Liter); platelet count \<= 100,000 /microliter (μL) (\<= 100 x 10\^9/Liter); absolute neutrophil count (\<= 1.5 x 10\^9/Liter).
* Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb).
* Presence of hepatitis C antibody at Screening. Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C Ribonucleic acid (RNA) test is obtained.
* Positive serology for Human Immunodeficiency Virus (HIV) 1 or 2.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months.
* History of alcohol or drug abuse, that would interfere with the ability to comply with the study or interfere with interpretation of the study, in the opinion of the Investigator.
* History of sensitivity to any of the study treatments, or components thereof, or a history of drug or other allergy that contraindicates their participation (including lidocaine or other local anesthetic), in the opinion of the Investigator or Medical Monitor.
* History of receiving a live or attenuated vaccine within 30 days of randomization OR plan to receive a live or attenuated vaccination during the study until completion of the follow-up visit.
* History of hypertrophic or keloid scarring.

Primary outcomes:
measure: Percentage (%) of Participants Who Achieved Greater Than or Equal (>=) to 75% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Percentage of Participants Who Achieved >=50% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants Who Achieved >=90% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants Who Achieved >=100% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Psoriasis Area Severity Index (PASI) Scores at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants Who Have a Static Investigator's Global Assessment (sIGA) Score of 0 or 1 at Week 12
timeFrame: At Week 12
measure: Change From Baseline in Psoriatic Body Surface Area (BSA) at Week 12
timeFrame: Baseline and Week 12
measure: Number of Participants With Any Adverse Events (AEs)
timeFrame: Up to Day 120
measure: Number of Participants With Drug Related AEs
timeFrame: Up to Day 120
measure: Number of Participants With Common (Occurring at Least 5%) Non Serious AEs
timeFrame: Up to Day 120
measure: Number of Participants With AEs Leading to Permanent Discontinuation of Study Intervention
timeFrame: Up to Day 120
measure: Number of Participants With SAEs Including Any SAEs, SAEs Related to Study Intervention, and Fatal SAEs
timeFrame: Up to Day 120
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Surrey
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Truro
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: London
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Oakville
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Peterborough
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: