A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic of GSK1070806 After a Single Intravenous Dose in Healthy Male and Female Caucasian, Chinese and Japanese Participants Aged 18 to 65 Years of Age Inclusive
- Registration Number
- NCT05590338
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This study is divided into two parts:
Part A of the study is double blinded, randomized, placebo-controlled and aims to assess the safety, tolerability, pharmacokinetics (PK) and Pharmacodynamic (PD) effect of a single intravenous (IV) infusion dose of GSK1070806 when administered to healthy participants of Japanese, Chinese and European/Caucasian ancestry.
Part B of the study is an open label single cohort arm to assess the safety, tolerability, PK and PD effect of a single IV bolus low dose of GSK1070806 in healthy participants of European/Caucasian ancestry.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
Inclusion Criteria
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring [12-lead Electrocardiogram (ECGs)]
- Between 18 and 65 years of age inclusive, at the time of signing the informed consent
- Body weight within the range 45 - 100 kilograms (kg) and body mass index (BMI) within the range 18-32 kilogram/meter square (kg/m^2) (inclusive)
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
- Is a woman of non-childbearing potential (WONCBP) OR
- Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective [with a failure rate of less than 1 percent (<1%) per year], with low user dependency
- Capable of giving signed informed consent
- Participants of Japanese ancestry are eligible based on meeting all of the following:
- Healthy male and female participants born in Japan
- Descendants of four ethnic Japanese grandparents and two ethnic Japanese parents
- Have lived outside Japan for less than 10 years at the time of screening
- Chinese participants are eligible based on meeting all of the following:
- Healthy male and female participants born in mainland China, Hong Kong, Macau or Taiwan
- Descendants of four ethnic Chinese grandparents and two ethnic Chinese parents
- Have lived outside mainland China, Hong Kong, Macau or Taiwan for less than 10 years at the time of screening
- Participants of Caucasian/European ancestry are eligible if they self-identify to be of Caucasian/European ancestry and have 2 parents of Caucasian/European ancestry and 4 grandparents of Caucasian/European ancestry
Exclusion Criteria
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, immunological, metabolic, musculoskeletal or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data
- Personal or family history of cardiomyopathy
- Known varicella, herpes zoster, or other severe viral infection within 6 weeks of anticipated dosing on Day 1. Or history of recurrent herpes reactivation in the past 2 years
- Evidence of active or latent tuberculosis (TB) as documented by medical history, examination, and TB testing with a positive (not indeterminate) QuantiFERON test
- History or evidence of clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, anaphylaxis, erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis)
- Lymphoma, leukemia, or any malignancy except for basal cell carcinomas of the skin that have been resected with no evidence of metastatic disease for 5 years
- Alanine transaminase (ALT) greater than (>) 1.5x upper limit of normal (ULN)
- Total bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or previous uncomplicated cholecystectomy more than 3 months ago)
- Corrected QT using Bazett's formula (QTcB) (Bazett) or Corrected QT using Fridericia's formula (QTcF) (Fridericia) interval >450 milli second (msec)
- History of Stevens Johnson Syndrome
- Known immunodeficiency
- Previous or current history of bleeding diathesis
- Intended use of over the counter or prescription medication including herbal medications within 7 days (or 14 days if the drug is a potential enzyme inducer) or five half-lives (whichever is longer) prior to dosing until final follow-up visit
- Live vaccine(s) or plans to receive such vaccines within 2 months of dosing until final follow-up visit
- Participation in the study would result in loss of blood or blood products in excess of 500 milli liter (mL) within 3 months
- Current enrollment or past participation in any other clinical study involving an investigational study intervention or any other type of medical research within the last 30 days, 5 half-lives or twice the duration of the known pharmacological/biological effect from the last dosing before dosing day in the current study
- Coronavirus strain 19 (COVID-19) (severe acute respiratory syndrome - Coronavirus-2 (SARS CoV-2)):
- Has had COVID-19 infection within 4 weeks of the initial screening visit
- Positive coronavirus test (COVID-19: SARS-CoV-2 Polymerase chain reaction (PCR) or rapid antigen test) at initial screening
- Signs and symptoms suggestive of COVID-19 (i.e., fever, cough, etc.) within 14 days of initial screening Known COVID-19-positive contacts within 14 days of initial Screening, at any time during the Screening Period, or within 14 days of dosing on Day 1
- Active substance abuse or a history of substance abuse within 6 months prior to the initial Screening visit. Substance abuse including cannabis is also prohibited during the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: GSK1070806 GSK1070806 Participants in Part A will receive single dose of GSK1070806 intravenous (IV) infusion Part A: Placebo Placebo Participants in Part A will receive single dose of placebo Part B: GSK1070806 GSK1070806 Participants in Part B will receive single dose of GSK1070806 IV bolus
- Primary Outcome Measures
Name Time Method Part A: Serum GSK1070806 area under the concentration-time curve from time zero extrapolated to infinity (AUC[0-β]) Up to Week 24 Part A: Number of participants with adverse events (AEs) and serious adverse events (SAEs) Up to Week 24 Part A: Serum GSK1070806 area under the concentration-time curve from time zero to the last quantifiable time (AUC(0-t)) Up to Week 24 Part A: Maximum observed serum concentration (Cmax) of GSK1070806 Up to Week 24
- Secondary Outcome Measures
Name Time Method Part B: Number of participants with AEs and SAEs Up to Week 32 Part A: Total IL-18 concentrations in serum Up to Week 24 Part B: Total IL-18 concentrations in serum Up to Week 32 Part B: Number of participants with ADA formation Up to Week 32 Part A: Number of participants with anti-drug antibody (ADA) formation Up to Week 24
Trial Locations
- Locations (1)
GSK Investigational Site
πΊπΈLas Vegas, Nevada, United States