Psoriasis
Conditions
Keywords
Plaque Psoriasis, Modified Release, GSK2982772, Skin Biopsy
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.
Interventions
DRUGGSK2982772
GSK2982772 will be available as MR tablet at a unit dose strength of 480 mg.
DRUGPlacebo
GSK2982772 matching placebo tablets will be administered via the oral route.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double-blind study where sponsor will be unblinded
Intervention model description
Participants will randomized in ratio of 2:1 to receive either 960 mg GSK2982772 or placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage (%) of Participants Who Achieved Greater Than or Equal (>=) to 75% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved >=50% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | Baseline and Week 12 | The 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% CrI was reported as a method of dispersion. |
| Percentage of Participants Who Achieved >=90% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | Baseline and Week 12 | The 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% CrI was reported as a method of dispersion. |
| Percentage of Participants Who Achieved >=100% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | Baseline and Week 12 | The 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% CrI was reported as a method of dispersion. |
| Change From Baseline in Psoriasis Area Severity Index (PASI) Scores at Week 12 | Baseline and Week 12 | The 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. Change from Baseline was calculated as post-Baseline visit values minus Baseline value. |
| Percentage of Participants Who Have a Static Investigator's Global Assessment (sIGA) Score of 0 or 1 at Week 12 | At Week 12 | Either investigator or his designee completed a global assessment of disease activity using the physician global assessment item. A 5-point scoring system was used to measure the severity of psoriatic lesions over the entire body at the time of evaluation. The 5-point scoring system ranging from 0 to 4 where 0 = Clear, 1 = Almost Clear, 2 = Mild, 3 = Moderate and 4=Severe. Percentage of participants who have a sIGA score of 0=clear or 1=almost clear at Week 12 was summarized. Note: The 95% CrI was reported as a method of dispersion. |
| Number of Participants With AEs Leading to Permanent Discontinuation of Study Intervention | Up to Day 120 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. All AEs which led to discontinuation of the study drug were reported. |
| Number of Participants With Any Adverse Events (AEs) | Up to Day 120 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. |
| Number of Participants With Drug Related AEs | Up to Day 120 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. The investigator was obligated to assess the relationship between study intervention and each occurrence of each AE. |
| Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Up to Day 120 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Non serious AEs are AEs that are not Serious Adverse Events (SAEs). All AEs occurring at least 5% in either arm were reported. Note: As both arms had small sample sizes, single occurrences of an AE met the 5% threshold for reporting. |
| Number of Participants With SAEs Including Any SAEs, SAEs Related to Study Intervention, and Fatal SAEs | Up to Day 120 | An SAE is defined as any untoward medical occurrence that, at any dose, results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement. All SAEs, SAEs related to the study drug, and fatal SAEs were reported. |
| Change From Baseline in Psoriatic Body Surface Area (BSA) at Week 12 | Baseline and Week 12 | The BSA affected with psoriasis was evaluated at all study visits by the Investigator or suitably trained delegate. As a reference, the area of the whole palm was counted as 1% BSA. Change from Baseline was calculated as Post-Baseline visit values minus Baseline value. |
Countries
Canada, Poland
Participant flow
Pre-assignment details
A total of 39 participants were screened, of which 29 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| GSK2982772 960 mg Participants received GSK2982772 960 mg oral tablets once daily for 12 weeks. | 19 |
| Placebo Participants received GSK2982772 matching placebo oral tablets once daily for 12 weeks. | 10 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | INVESTIGATOR DISCRETION | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | SUBJECT REACHED PROTOCOL-DEFINED STOPPING CRITERIA | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | GSK2982772 960 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 50.1 YEARS STANDARD_DEVIATION 15.97 | 46.5 YEARS STANDARD_DEVIATION 12.52 | 48.8 YEARS STANDARD_DEVIATION 14.74 |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Mixed race | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Mixed White race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 17 Participants | 9 Participants | 26 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 16 Participants | 5 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 10 |
| other Total, other adverse events | 11 / 19 | 6 / 10 |
| serious Total, serious adverse events | 1 / 19 | 0 / 10 |
Outcome results
Primary
Percentage (%) of Participants Who Achieved Greater Than or Equal (>=) to 75% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at 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.
Time frame: Baseline and Week 12
Population: The analysis was performed on the Intent to Treat Set that includes all participants who were randomized to study intervention in the study and who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2982772 960 mg | Percentage (%) of Participants Who Achieved Greater Than or Equal (>=) to 75% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | 5 Percentage of Participants |
| Placebo | Percentage (%) of Participants Who Achieved Greater Than or Equal (>=) to 75% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | 0 Percentage of Participants |
Comparison: Bayesian logistic regression. An informative prior was used for the placebo response in this statistical analysis, the prior for placebo response rate was of the form: 90% weight on Be (5.39, 69) and 10% on Be (1/3,1/3). The prior was derived from historical data from similar clinical trials using meta-analytic predictive prior (MAP) approach. All other parameters took vague priors.95% CI: [-9.19, 8.28]Bayesian Logistic Regression Model
95% CI: [-4.81, 8.07]Bayesian Logistic Regression Model
Secondary
Change From Baseline in Psoriasis Area Severity Index (PASI) Scores at Week 12
The 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. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
Time frame: Baseline and Week 12
Population: The analysis was performed on the Intent to Treat Set that includes all participants who were randomized to study intervention in the study and who received at least one dose of study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK2982772 960 mg | Change From Baseline in Psoriasis Area Severity Index (PASI) Scores at Week 12 | -8.82 Scores on a Scale | Standard Deviation 4.501 |
| Placebo | Change From Baseline in Psoriasis Area Severity Index (PASI) Scores at Week 12 | -6.98 Scores on a Scale | Standard Deviation 5.228 |
Secondary
Change From Baseline in Psoriatic Body Surface Area (BSA) at Week 12
The BSA affected with psoriasis was evaluated at all study visits by the Investigator or suitably trained delegate. As a reference, the area of the whole palm was counted as 1% BSA. Change from Baseline was calculated as Post-Baseline visit values minus Baseline value.
Time frame: Baseline and Week 12
Population: The analysis was performed on the Intent to Treat Set that includes all participants who were randomized to study intervention in the study and who received at least one dose of study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK2982772 960 mg | Change From Baseline in Psoriatic Body Surface Area (BSA) at Week 12 | -5.2 Percentage of Body Surface Area | Standard Deviation 6.3 |
| Placebo | Change From Baseline in Psoriatic Body Surface Area (BSA) at Week 12 | -3.7 Percentage of Body Surface Area | Standard Deviation 4.41 |
Secondary
Number of Participants With AEs Leading to Permanent Discontinuation of Study Intervention
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. All AEs which led to discontinuation of the study drug were reported.
Time frame: Up to Day 120
Population: The analysis was performed on the Safety Set that included all participants in the enrolled population who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK2982772 960 mg | Number of Participants With AEs Leading to Permanent Discontinuation of Study Intervention | 2 Participants |
| Placebo | Number of Participants With AEs Leading to Permanent Discontinuation of Study Intervention | 2 Participants |
Secondary
Number of Participants With Any Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
Time frame: Up to Day 120
Population: The analysis was performed on the Safety Set that included all participants in the enrolled population who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK2982772 960 mg | Number of Participants With Any Adverse Events (AEs) | 12 Participants |
| Placebo | Number of Participants With Any Adverse Events (AEs) | 6 Participants |
Secondary
Number of Participants With Common (Occurring at Least 5%) Non Serious AEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Non serious AEs are AEs that are not Serious Adverse Events (SAEs). All AEs occurring at least 5% in either arm were reported. Note: As both arms had small sample sizes, single occurrences of an AE met the 5% threshold for reporting.
Time frame: Up to Day 120
Population: The analysis was performed on the Safety Set that included all participants in the enrolled population who received at least one dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Neutrophil count decreased | 1 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Alanine aminotransferase increased | 0 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | White blood cell count decreased | 1 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Dry eye | 1 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Back pain | 2 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Aspartate aminotransferase increased | 0 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Headache | 3 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Allergy to arthropod sting | 1 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Suicidal ideation | 0 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Blood creatinine abnormal | 1 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Nasal congestion | 0 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Tinnitus | 1 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Intertrigo | 0 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Creatinine renal clearance abnormal | 2 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Pruritus | 0 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Herpes zoster | 1 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Psoriasis | 1 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Hepatitis E antibody positive | 0 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Rash | 0 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Diarrhea | 1 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Hypertension | 0 Participants |
| GSK2982772 960 mg | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Neutropenia | 1 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Hypertension | 1 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Neutropenia | 0 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Tinnitus | 0 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Dry eye | 0 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Diarrhea | 1 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Allergy to arthropod sting | 0 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Herpes zoster | 0 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Alanine aminotransferase increased | 1 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Aspartate aminotransferase increased | 1 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Blood creatinine abnormal | 0 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Creatinine renal clearance abnormal | 0 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Hepatitis E antibody positive | 1 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Neutrophil count decreased | 0 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | White blood cell count decreased | 0 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Back pain | 1 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Headache | 3 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Suicidal ideation | 1 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Nasal congestion | 1 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Intertrigo | 1 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Pruritus | 1 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Psoriasis | 0 Participants |
| Placebo | Number of Participants With Common (Occurring at Least 5%) Non Serious AEs | Rash | 1 Participants |
Secondary
Number of Participants With Drug Related AEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. The investigator was obligated to assess the relationship between study intervention and each occurrence of each AE.
Time frame: Up to Day 120
Population: The analysis was performed on the Safety Set that included all participants in the enrolled population who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK2982772 960 mg | Number of Participants With Drug Related AEs | 5 Participants |
| Placebo | Number of Participants With Drug Related AEs | 4 Participants |
Secondary
Number of Participants With SAEs Including Any SAEs, SAEs Related to Study Intervention, and Fatal SAEs
An SAE is defined as any untoward medical occurrence that, at any dose, results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement. All SAEs, SAEs related to the study drug, and fatal SAEs were reported.
Time frame: Up to Day 120
Population: The analysis was performed on the Safety Set that included all participants in the enrolled population who received at least one dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2982772 960 mg | Number of Participants With SAEs Including Any SAEs, SAEs Related to Study Intervention, and Fatal SAEs | All SAEs | 1 Participants |
| GSK2982772 960 mg | Number of Participants With SAEs Including Any SAEs, SAEs Related to Study Intervention, and Fatal SAEs | Study drug related SAE | 1 Participants |
| GSK2982772 960 mg | Number of Participants With SAEs Including Any SAEs, SAEs Related to Study Intervention, and Fatal SAEs | Fatal SAE | 0 Participants |
| Placebo | Number of Participants With SAEs Including Any SAEs, SAEs Related to Study Intervention, and Fatal SAEs | All SAEs | 0 Participants |
| Placebo | Number of Participants With SAEs Including Any SAEs, SAEs Related to Study Intervention, and Fatal SAEs | Study drug related SAE | 0 Participants |
| Placebo | Number of Participants With SAEs Including Any SAEs, SAEs Related to Study Intervention, and Fatal SAEs | Fatal SAE | 0 Participants |
Secondary
Percentage of Participants Who Achieved >=100% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12
The 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% CrI was reported as a method of dispersion.
Time frame: Baseline and Week 12
Population: The analysis was performed on the Intent to Treat Set that includes all participants who were randomized to study intervention in the study and who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2982772 960 mg | Percentage of Participants Who Achieved >=100% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | 0 Percentage of Participants |
| Placebo | Percentage of Participants Who Achieved >=100% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | 0 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved >=50% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12
The 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% CrI was reported as a method of dispersion.
Time frame: Baseline and Week 12
Population: The analysis was performed on the Intent to Treat Set that includes all participants who were randomized to study intervention in the study and who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2982772 960 mg | Percentage of Participants Who Achieved >=50% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | 42 Percentage of Participants |
| Placebo | Percentage of Participants Who Achieved >=50% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | 20 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved >=90% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12
The 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% CrI was reported as a method of dispersion.
Time frame: Baseline and Week 12
Population: The analysis was performed on the Intent to Treat Set that includes all participants who were randomized to study intervention in the study and who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2982772 960 mg | Percentage of Participants Who Achieved >=90% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | 0 Percentage of Participants |
| Placebo | Percentage of Participants Who Achieved >=90% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12 | 0 Percentage of Participants |
Secondary
Percentage of Participants Who Have a Static Investigator's Global Assessment (sIGA) Score of 0 or 1 at Week 12
Either investigator or his designee completed a global assessment of disease activity using the physician global assessment item. A 5-point scoring system was used to measure the severity of psoriatic lesions over the entire body at the time of evaluation. The 5-point scoring system ranging from 0 to 4 where 0 = Clear, 1 = Almost Clear, 2 = Mild, 3 = Moderate and 4=Severe. Percentage of participants who have a sIGA score of 0=clear or 1=almost clear at Week 12 was summarized. Note: The 95% CrI was reported as a method of dispersion.
Time frame: At Week 12
Population: The analysis was performed on the Intent to Treat Set that includes all participants who were randomized to study intervention in the study and who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2982772 960 mg | Percentage of Participants Who Have a Static Investigator's Global Assessment (sIGA) Score of 0 or 1 at Week 12 | 11 Percentage of Participants |
| Placebo | Percentage of Participants Who Have a Static Investigator's Global Assessment (sIGA) Score of 0 or 1 at Week 12 | 0 Percentage of Participants |