PsoriasisPhase 2NCT02776033
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Repeat Doses of GSK2982772 in Subjects With Psoriasis
A Phase 2 study testing GSK2982772 in people with Psoriasis, run by GlaxoSmithKline at 4 sites in Canada.
Trial summary
This is the first study with GSK2982772, a receptor-interacting protein-1 (RIP1) kinase inhibitor, in subjects with active plaque-type psoriasis (PsO). The primary objective will be to investigate the safety and tolerability of repeat oral doses of GSK2982772 60 milligram (mg) twice daily (BID) for 84 days in Cohort 1… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Psoriasis
- What is being tested?
- GSK2982772
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 4 sitesCanada
- Study dates
- 30 Aug 2016to 4 Jan 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Between 18 and 75 years of age inclusive, at the time of signing the informed consent.
- Subjects who do not have any medical conditions, other than active plaque-type psoriasis, that in the opinion of the Investigator put the subject at unacceptable risk or interfere with study assessments or integrity of the data. All medical conditions must be stable for the duration of the study.
- Presence of active chronic plaque-type psoriasis as determined by the Investigator for at least 6 months (confirmed by the subject or medical record) before first dose of study treatment (Day 1).
- Subject has psoriasis plaques involving Body Surface Area >=3% assessed at screening and before dosing on Day 1.
- Physician Global Assessment >=3.
- Subject must agree to avoid prolonged exposure to natural sunlight, tanning beds or phototherapy devices for the duration of the study
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- Subject has at least two stable plaques assessed at screening and before dosing on Day 1:
- Both must be of a suitable size (>=3 centimeter [cm] by 3 cm) and one in a site suitable for repeat biopsy, and one in a site suitable for index lesion PLSS scoring.
- Both plaques must have a PLSS lesional score >=2 for the induration component (moderate or above), >=1 for erythema and scaling with a total score of >=5.
- The biopsy lesion must not be on the face, groin, scalp, knees, elbows, or on the palmar/plantar surfaces of the hands/feet, and must be shielded from natural light with clothing.
- Subject is naive to any biologic therapies for psoriasis, OR has had previous exposure to a single anti- TNF biologic agent in the context of a previous clinical trial. The anti-TNF biologic agent must have been discontinued more than 8 weeks prior to screening visit (12 Weeks or 5 half lives whichever is longer from first dose).
- A body mass index within the range of 18.5-35 kilogram per meter square (kg)/m^2 (inclusive).
- Male and Female subjects:
- Males: Male subjects with female partners of child bearing potential must comply with the pre specified contraception requirements.
- Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotropin test), not lactating, and is either of non-reproductive potential or reproductive potential. If of reproductive potential, then the subject should agree to follow one of the options listed per GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential from 30 days prior to the first dose and until 30 days after the last dose of study medication The Investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
- Capable of giving signed informed consent
Who cannot join
- Subjects with clinically overt concurrent psoriatic arthritis who are receiving chronic disease-modifying anti-rheumatic medications therapy (other than non-steroidal anti-inflammatory drug), as judged by the Investigator.
- Has nonplaque forms of psoriasis (e.g. erythrodermic, guttate, or pustular), as judged by the Investigator.
- Has current drug-induced psoriasis (e.g., a new onset of psoriasis or an exacerbation from beta blockers, calcium channel blockers, or lithium).
- Subject with current history of Suicidal Ideation Behaviour as measured using the Columbia Suicide Severity Rating Scale or a history of attempted suicide.
- An active infection, or a history of infections as follows:
- Hospitalization for treatment of infection within 60 days before first dose (Day 1).
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- Currently on any suppressive therapy for a chronic infection (such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria).
- Use of parenteral (intravenous or intramuscular) antibiotics (antibacterials, antivirals, antifungals, or antiparasitic agents) within 60 days before first dose.
- A history of opportunistic infections within 1 year of screening (e.g. pneumocystis jirovecii, cytomegalovirus, 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.
- Recurrent or chronic infection or other active infection that, in the opinion of the Investigator might cause this study to be detrimental to the subject.
- History of tuberculosis (TB), irrespective of treatment status. A positive diagnostic TB test at screening defined as a positive QuantiFERON-TB Gold test or T-spot test.
- In cases where the QuantiFERON or T-spot test is indeterminate, the subject may have the test repeated once, but they will not be eligible for the study unless the second test is negative.
- In cases where the QuantiFERON or T-spot test is positive, but a locally-read follow up chest X-ray, shows no evidence of current or previous pulmonary tuberculosis, the subject may be eligible for the study at the discretion of the Investigator and medical monitor.
- ECG for heart rate QTc >450 milliseconds (msec) or QTc >480 msec in subjects with bundle branch block.
- Alanine aminotransferase >2×upper limit of normal (ULN) and bilirubin >1.5×ULN (isolated bilirubin >1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Current or history of renal disease or estimated glomerular filtrate rate by Chronic Kidney Disease Epidemiology Collaboration equation <60 mL/min/1.73 m^2.
- Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.
- A major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
- 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 carcinoma) or carcinoma in situ of the uterine cervix that has been fully treated and shows no evidence of recurrence.
- A history of hypertrophic scarring or keloid formation, or known allergy to lidocaine or other local anaesthetics.
- The subject has received treatment with the specified therapies listed in the protocol, 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 in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject safety.
- History of alcohol or drug abuse that would interfere with the ability to comply with the study.
- Subject intends to sunbathe or use a tanning device (sun bed or solarium) within 14 days prior to Day 1 and until completion of the follow up visit (Day 112).
- History of sensitivity to any of the study treatments, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
- Received a live or attenuated vaccine within 30 days of randomization OR plan to receive a vaccination during the study until completion of the follow-up visit.
- The subject has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives, whichever is longer 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. Subjects who were randomized into Cohort 1 are not eligible to be re-randomized into Cohort 2.
- Hemoglobin <11 g/deciliter (dL); hematocrit <30%, white blood cell count =<3,000/millimeter (mm)^3 (<=3.0×10^9/L) ; platelet count <=100,000/microliter (µL) (<=100 × 10^9/L); absolute neutrophil count <=1.5×10^9/L at the screening visit.
- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. As potential for and magnitude of immunosuppression with this compound is unknown, subjects with presence of hepatitis B core antibody (HBcAb) should be excluded. Subjects positive for HBsAg and/or positive for anti-HBcAb (regardless of anti-HBs antibody status) are excluded.
- A positive serology for human immunodeficiency virus 1 or 2 at screening.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months.
- Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
GSK Investigational Site
Markham, Ontario, L3P1X2
GSK Investigational Site
Montreal, Quebec, H2K 4L5
GSK Investigational Site
Peterborough, Ontario, K9J 5K2
GSK Investigational Site
Waterloo, Ontario, N2J 1C4
About this study
Official title: A Multicentre, Randomised, Double-blind (Sponsor-unblinded), Placebo-controlled, Repeat Dose Study to Investigate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of GSK2982772 in Subjects With Active Plaque-type Psoriasis
This is the first study with GSK2982772, a receptor-interacting protein-1 (RIP1) kinase inhibitor, in subjects with active plaque-type psoriasis (PsO). The primary objective will be to investigate the safety and tolerability of repeat oral doses of GSK2982772 60 milligram (mg) twice daily (BID) for 84 days in Cohort 1 and 60 mg thrice daily (TID) for 84 days in Cohort 2. In addition, a number of experimental and clinical endpoints will be employed to obtain information on the pharmacokinetics, pharmacodynamics, and efficacy in subjects with active PsO. There will be two Cohorts of subjects. In Cohort 1 after a screening period of up to 30 days, approximately 30 subjects will be randomized to receive either GSK2982772 60 mg BID or placebo for 84 days (12 Weeks), followed by a follow-up period (28 days). In Cohort 2 after a screening period of up to 30 days, approximately 24 subjects will be randomized to receive either GSK2982772 60 mg TID or placebo for 84 days (12 Weeks), followed by a follow-up period (28 days). The total duration of participation is approximately 20 Weeks from screening to the last study visit.
- Conditions
- Psoriasis
- Being tested
- GSK2982772, Placebo
- Keywords
- tolerability, safety, GSK2982772, RIP1 kinase inhibitor, psoriasis
- Medical subject headings
- Psoriasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2982772Drug
GSK2982772 will be supplied as a white to almost white, round, film coated 30 mg oral tablets; two tablets to be taken in the morning and two in the evening, as directed for Cohort 1 and for Cohort 2 two tablets to be taken three times daily as directed.
PlaceboDrug
Matching placebo will be supplied as a white to almost white, round film coated tablets; two tablets to be taken in the morning and two in the evening, as directed for Cohort 1 and for Cohort 2 two tablets to be taken three times daily as directed.
| Study group | Role | What they receive |
|---|---|---|
| GSK2982772 receivers in Cohort 1 | Experimental | Randomized subjects will receive GSK2982772 BID (approximately 12 hours apart) via oral route for 84 days. Receives: Drug: GSK2982772 |
| Placebo receivers in Cohort 1 | Placebo comparator | Randomized subjects will receive placebo BID via oral route for 84 days. Receives: Drug: Placebo |
| GSK2982772 receivers in Cohort 2 | Experimental | Randomized subjects will receive GSK2982772 TID (approximately 8 hours apart) via oral route for 84 days Receives: Drug: GSK2982772 |
| Placebo receivers in Cohort 2 | Placebo comparator | Randomized subjects will receive placebo TID via oral route for 84 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least one dose of study treatment.
Measured: Up to Day 116
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Blood samples were collected for analysis of clinical chemistry parameters. Clinical concern ranges were >=2x Upper Limit of Normal (ULN) units per liter (U/L) for alanine aminotransferase (ALT), <30 millimoles per liter (mmol/L) for albumin, >=2x ULN U/L for alkaline phosphatase, >=2x ULN U/L for aspartate aminotransferase (AST), <2 or >2.75 mmol/L for Calcium, >44.2 mmol/L for Creatinine, <3 or >9 mmol/L for Glucose, <3 or>5.5 mmol/L for Potassium, <130 or >150 mmol/L for Sodium, and >=1.5xULN micromoles per liter for total bilirubin. Participants were counted in worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (example given [e.g.], High to High), or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High', Baseline is defined as the latest pre-dose assessment.
Measured: Up to Day 116
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Blood samples were collected for analysis of hematology parameters. Clinical concern ranges were >0.54 calculated as proportion of red blood cells in blood for Hematocrit, >180 grams per liter for Hemoglobin, <0.8 x10^9 cells per liter for Lymphocytes, <1.5 x10^9 cells per liter for Neutrophil count, <100 or >550 x10^9 cells per liter for Platelet count and <3 or >20 x10^9 cells per liter White Blood Cell count. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment.
Measured: Up to Day 116
Change From Baseline in Urine Potential of Hydrogen (pH)
Urine samples were collected for measurement of urine pH at indicated time points. pH is a measure of hydrogen ion concentration and used to determine the acidity or alkalinity of urine. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Measured: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116)
Change From Baseline in Urine Specific Gravity
Urine samples were collected to analyze specific gravity of urine. Specific gravity, is a measure of urine concentration and is measured using a chemical test. Specific gravity measurements provide a comparison of the amount of substances dissolved in urine as compared to pure water. If there were no solutes present, the specific gravity of urine would be 1.000 the same as pure water. Specific gravity between 1.002 and 1.035 could be considered as normal. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Measured: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116)
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Blood pressure was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Measured: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)
Change From Baseline in Heart Rate
Heart rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Measured: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)
Change From Baseline in Respiratory Rate
Respiratory rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Measured: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)
Change From Baseline in Body Temperature
Body temperature was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Measured: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)
Number of Participants With Any Time Post-Baseline Results for Electrocardiogram Findings
Single 12-lead electrocardiograms were obtained at indicated time points during the study using an electrocardiogram machine that automatically calculates the heart rate and measures PR, QRS, QT, QT interval corrected for heart rate (QTc) using Bazett's formula (QTcB) intervals and QTc using Fridericia's formula (QTcF). The abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Baseline is defined as the latest pre-dose assessment. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. The number of participants with normal and abnormal electrocardiogram findings at any time post-Baseline visit has been presented.
Measured: Up to Day 116
Secondary outcomes (8)
Plasma Concentrations of GSK2982772 at Days 43 and 85
Blood samples were collected for pharmacokinetic analysis of GSK2982772 following 60 mg BID and 60 mg TID dose at indicated time points. The pharmacokinetic analysis was performed using non-compartmental methods. The analysis was based on Pharmacokinetic Population which comprised of participants in the 'Safety' Population for whom a pharmacokinetic sample was obtained and analyzed.
Measured: Day 43 (Pre-dose) and Day 85
Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43
Blood samples were collected for pharmacokinetic analysis of GSK2982772 following 60 mg BID and 60 mg TID dose at indicated time points. The pharmacokinetic analysis was performed using non-compartmental methods.
Measured: 1, 2, 4 and 6 Hours Post-dose on Days 1 and 43
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772
A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of Cluster of differentiation 11 (CD11+), CD161+, CD3+ and Elastase. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Data for all the listed biomarkers from skin biopsy has been presented for two skin types; dermis and epidermis at Day 43. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses. NA indicates that data was not available as geometric coefficient of variation could not be calculated for single participant.
Measured: Baseline (Pre-dose on Day 1) and Day 43
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy: Epidermis Thickness
A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of epidermis thickness. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses.
Measured: Baseline (Pre-dose on Day 1) and Day 43
Number of Participants With Changes in Keratin 16 (K16) Histopathological Scoring in Psoriatic Lesional Biopsies
A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of K16 as keratin expression. Baseline is defined as the latest pre-dose assessment. Results for K16 were categorized as, negative to positive, no change and positive to negative at Day 43. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses.
Measured: Baseline (Pre-dose on Day 1) and Day 43
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
A target lesion for biopsy was identified on the trunk or extremities at indicated time points. mRNA expression of inflammatory markers and tissue healing were assessed. Data has been presented for inflammatory gene transcripts including interferon gamma, interleukin 10, interleukin 17A, interleukin 21, interleukin 22, interleukin 23 subunit alpha, interleukin 4 and tumor necrosis factor. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses.
Measured: Day 1 and Day 43
Percentage Change From Baseline Psoriatic Lesion Severity Sum (PLSS) Scores in the Index Lesion Following Administration of GSK2982772
Two plaques were selected, one for clinical assessment (index plaque) and one for biopsy. Each lesion was evaluated for 3 components: erythema, induration, and scaling. Each component was given a score using a scale ranging from 0 (no symptom) to 4 (very marked) with increasing score reflecting increased lesion severity. The PLSS is the sum of the erythema, scaling and plaque thickness scores. The total PLSS score ranged from 0 (no symptom) to 12 (very marked). Each lesion must have a PLSS score of >=5. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all efficacy analyses.
Measured: Baseline (Pre-dose on Day 1) and Days 15, 29, 43, 57, 71, 85
Actual PLSS Scores in the Index Psoriatic Lesion Following Administration of GSK2982772
Two plaques were selected one for clinical assessment (index plaque) and one for biopsy. Each lesion was evaluated for 3 components: erythema, induration, and scaling. Each component was given a score using a scale ranging from 0 (no symptom) to 4 (very marked) with increasing score reflecting increased lesion severity. The PLSS is the sum of the erythema, scaling and plaque thickness scores. The total PLSS score ranged from 0 (no symptom) to 12 (very marked). Each lesion must have a PLSS score of >=5. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all efficacy analyses.
Measured: Days 1, 15, 29, 43, 57, 71 and 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2016 (estimated)
- Study start30 Aug 2016
- Primary completion4 Jan 2018
- Study completion4 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PsoriasisStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02776033
- Sponsor's protocol ID
- 203167
- Status last verified
- Jun 2020
- First submitted
- 16 May 2016
- Last updated
- 8 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Weisel K, Berger S, Papp K, Maari C, Krueger JG, Scott N, Tompson D, Wang S, Simeoni M, Bertin J, Peter Tak P. Response to Inhibition of Receptor-Interacting Protein Kinase 1 (RIPK1) in Active Plaque Psoriasis: A Randomized Placebo-Controlled Study. Clin Pharmacol Ther. 2020 Oct;108(4):808-816. doi: 10.1002/cpt.1852. Epub 2020 Jul 7.
PubMed 32301501
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Randomised, Double-blind (Sponsor-unblinded), Placebo-controlled, Repeat Dose Study to Investigate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of GSK2982772 in Subjects With Active Plaque-type Psoriasis
- ClinicalTrials.gov ID
- NCT02776033
- Acronym / sponsor ID
- 203167
- Conditions
- Psoriasis
- Keywords
- tolerability, safety, GSK2982772, RIP1 kinase inhibitor, psoriasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 30 Aug 2016 (actual)
- Primary completion
- 4 Jan 2018 (actual)
- Study completion
- 4 Jan 2018 (actual)
- First posted
- 18 May 2016 (estimated)
- Results
- Posted 22 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is the first study with GSK2982772, a receptor-interacting protein-1 (RIP1) kinase inhibitor, in subjects with active plaque-type psoriasis (PsO). The primary objective will be to investigate the safety and tolerability of repeat oral doses of GSK2982772 60 milligram (mg) twice daily (BID) for 84 days in Cohort 1 and 60 mg thrice daily (TID) for 84 days in Cohort 2. In addition, a number of experimental and clinical endpoints will be employed to obtain information on the pharmacokinetics, pharmacodynamics, and efficacy in subjects with active PsO. There will be two Cohorts of subjects. In Cohort 1 after a screening period of up to 30 days, approximately 30 subjects will be randomized to receive either GSK2982772 60 mg BID or placebo for 84 days (12 Weeks), followed by a follow-up period (28 days). In Cohort 2 after a screening period of up to 30 days, approximately 24 subjects will be randomized to receive either GSK2982772 60 mg TID or placebo for 84 days (12 Weeks), followed by a follow-up period (28 days). The total duration of participation is approximately 20 Weeks from screening to the last study visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GSK2982772 receivers in Cohort 1 | Experimental | Drug: GSK2982772Randomized subjects will receive GSK2982772 BID (approximately 12 hours apart) via oral route for 84 days. |
| Placebo receivers in Cohort 1 | Placebo comparator | Drug: PlaceboRandomized subjects will receive placebo BID via oral route for 84 days. |
| GSK2982772 receivers in Cohort 2 | Experimental | Drug: GSK2982772Randomized subjects will receive GSK2982772 TID (approximately 8 hours apart) via oral route for 84 days |
| Placebo receivers in Cohort 2 | Placebo comparator | Drug: PlaceboRandomized subjects will receive placebo TID via oral route for 84 days. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Between 18 and 75 years of age inclusive, at the time of signing the informed consent.
- Subjects who do not have any medical conditions, other than active plaque-type psoriasis, that in the opinion of the Investigator put the subject at unacceptable risk or interfere with study assessments or integrity of the data. All medical conditions must be stable for the duration of the study.
- Presence of active chronic plaque-type psoriasis as determined by the Investigator for at least 6 months (confirmed by the subject or medical record) before first dose of study treatment (Day 1).
- Subject has psoriasis plaques involving Body Surface Area >=3% assessed at screening and before dosing on Day 1.
- Physician Global Assessment >=3.
Key exclusion criteria (34 listed)
- Subjects with clinically overt concurrent psoriatic arthritis who are receiving chronic disease-modifying anti-rheumatic medications therapy (other than non-steroidal anti-inflammatory drug), as judged by the Investigator.
- Has nonplaque forms of psoriasis (e.g. erythrodermic, guttate, or pustular), as judged by the Investigator.
- Has current drug-induced psoriasis (e.g., a new onset of psoriasis or an exacerbation from beta blockers, calcium channel blockers, or lithium).
- Subject with current history of Suicidal Ideation Behaviour as measured using the Columbia Suicide Severity Rating Scale or a history of attempted suicide.
- An active infection, or a history of infections as follows:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK2982772GSK2982772 will be supplied as a white to almost white, round, film coated 30 mg oral tablets; two tablets to be taken in the morning and two in the evening, as directed for Cohort 1 and for Cohort 2 two tablets to be taken three times daily as directed. | Drug | GSK2982772 receivers in Cohort 1, GSK2982772 receivers in Cohort 2 |
| PlaceboMatching placebo will be supplied as a white to almost white, round film coated tablets; two tablets to be taken in the morning and two in the evening, as directed for Cohort 1 and for Cohort 2 two tablets to be taken three times daily as directed. | Drug | Placebo receivers in Cohort 1, Placebo receivers in Cohort 2 |
Primary outcome
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
Time frame: Up to Day 116
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least one dose of study treatment.
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Time frame: Up to Day 116
Blood samples were collected for analysis of clinical chemistry parameters. Clinical concern ranges were >=2x Upper Limit of Normal (ULN) units per liter (U/L) for alanine aminotransferase (ALT), <30 millimoles per liter (mmol/L) for albumin, >=2x ULN U/L for alkaline phosphatase, >=2x ULN U/L for aspartate aminotransferase (AST), <2 or >2.75 mmol/L for Calcium, >44.2 mmol/L for Creatinine, <3 or >9 mmol/L for Glucose, <3 or>5.5 mmol/L for Potassium, <130 or >150 mmol/L for Sodium, and >=1.5xULN micromoles per liter for total bilirubin. Participants were counted in worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (example given [e.g.], High to High), or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High', Baseline is defined as the latest pre-dose assessment.
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Time frame: Up to Day 116
Blood samples were collected for analysis of hematology parameters. Clinical concern ranges were >0.54 calculated as proportion of red blood cells in blood for Hematocrit, >180 grams per liter for Hemoglobin, <0.8 x10^9 cells per liter for Lymphocytes, <1.5 x10^9 cells per liter for Neutrophil count, <100 or >550 x10^9 cells per liter for Platelet count and <3 or >20 x10^9 cells per liter White Blood Cell count. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment.
Change From Baseline in Urine Potential of Hydrogen (pH)
Time frame: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116)
Urine samples were collected for measurement of urine pH at indicated time points. pH is a measure of hydrogen ion concentration and used to determine the acidity or alkalinity of urine. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Change From Baseline in Urine Specific Gravity
Time frame: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116)
Urine samples were collected to analyze specific gravity of urine. Specific gravity, is a measure of urine concentration and is measured using a chemical test. Specific gravity measurements provide a comparison of the amount of substances dissolved in urine as compared to pure water. If there were no solutes present, the specific gravity of urine would be 1.000 the same as pure water. Specific gravity between 1.002 and 1.035 could be considered as normal. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)
Blood pressure was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Change From Baseline in Heart Rate
Time frame: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)
Heart rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Change From Baseline in Respiratory Rate
Time frame: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)
Respiratory rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Change From Baseline in Body Temperature
Time frame: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)
Body temperature was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Number of Participants With Any Time Post-Baseline Results for Electrocardiogram Findings
Time frame: Up to Day 116
Single 12-lead electrocardiograms were obtained at indicated time points during the study using an electrocardiogram machine that automatically calculates the heart rate and measures PR, QRS, QT, QT interval corrected for heart rate (QTc) using Bazett's formula (QTcB) intervals and QTc using Fridericia's formula (QTcF). The abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Baseline is defined as the latest pre-dose assessment. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. The number of participants with normal and abnormal electrocardiogram findings at any time post-Baseline visit has been presented.
8 secondary outcomes
Plasma Concentrations of GSK2982772 at Days 43 and 85
Time frame: Day 43 (Pre-dose) and Day 85
Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43
Time frame: 1, 2, 4 and 6 Hours Post-dose on Days 1 and 43
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772
Time frame: Baseline (Pre-dose on Day 1) and Day 43
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy: Epidermis Thickness
Time frame: Baseline (Pre-dose on Day 1) and Day 43
Number of Participants With Changes in Keratin 16 (K16) Histopathological Scoring in Psoriatic Lesional Biopsies
Time frame: Baseline (Pre-dose on Day 1) and Day 43
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Time frame: Day 1 and Day 43
Percentage Change From Baseline Psoriatic Lesion Severity Sum (PLSS) Scores in the Index Lesion Following Administration of GSK2982772
Time frame: Baseline (Pre-dose on Day 1) and Days 15, 29, 43, 57, 71, 85
Actual PLSS Scores in the Index Psoriatic Lesion Following Administration of GSK2982772
Time frame: Days 1, 15, 29, 43, 57, 71 and 85
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32301501Weisel K, Berger S, Papp K, Maari C, Krueger JG, Scott N, Tompson D, Wang S, Simeoni M, Bertin J, Peter Tak P. Response to Inhibition of Receptor-Interacting Protein Kinase 1 (RIPK1) in Active Plaque Psoriasis: A Randomized Placebo-Controlled Study. Clin Pharmacol Ther. 2020 Oct;108(4):808-816. doi: 10.1002/cpt.1852. Epub 2020 Jul 7.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK2982772 in people with Psoriasis, run by GlaxoSmithKline at 4 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs (time frame: Up to Day 116). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02776033, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2020.