Scleroderma, Systemic
Conditions
Keywords
GSK2330811, Dose Escalation, Safety, First Time in Human, Pharmacodynamics, Pharmacokinetics
Brief summary
GSK2330811 is a humanised monoclonal antibody, that blocks Oncostatin M (OSM), which is being developed for the treatment of inflammatory and fibrotic diseases. This first time in human study will evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and immunogenicity profile of single ascending subcutaneous (s.c.) doses of GSK2330811, in healthy subjects. This study will be a randomised, double-blind (sponsor open), placebo-controlled, single centre, single dose escalation study of s.c. administrations of GSK2330811 in healthy subjects. Approximately 40 subjects will be enrolled in the study, across 5 cohorts. Each cohort is planned to consist of 8 subjects, randomised such that 6 subjects will receive GSK2330811 and 2 subjects will receive placebo. The starting dose for the study will be 0.1 milligram (mg)/kilogram (kg) s.c. single dose and the highest dose will be 6 mg/kg s.c. single dose. Subjects will be admitted to the clinical unit on the day prior to dosing (Day -1). On Day 1, each subject will receive a s.c. dose of GSK2330811 or placebo. Subjects will then remain as an in-patient until discharged on Day 8, after assessments have been performed. The duration of the study, including screening, is approximately 19 weeks for Cohorts 1 to 4 and 23 weeks for Cohort 5.
Interventions
DRUGGSK2330811
GSK2330811 will be supplied as clear or opalescent, colourless, yellow to brown liquid administered as single dose s.c.
DRUGPlacebo
Placebo will be supplied as Normal Saline (0.9% weight by volume \[w/v\] Sodium Chloride) administered as single dose s.c.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Between 18 and 65 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, vital signs and a 12-lead ECG. * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Cohorts 1-4: Body weight \<=100 kg and body mass index (BMI) within the range 18.5 - 29.9 kilogram per meter square (kg/m\^2) (inclusive); Cohort 5: Body weight \<=80 kg and BMI within the range 18.5 - 29.9 kg/m\^2 (inclusive). * Female subjects are eligible to participate if not pregnant (as confirmed by a negative serum \[screening\] and urine \[Day -1\] human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies: * Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy. * Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. * Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 15 weeks after dosing of study medication: * Vasectomy with documentation of azoospermia. * Male condom plus partner use of one of the contraceptive options as follows: Contraceptive subdermal implant that meets the Standard Operating Procedure (SOP) effectiveness criteria including a \<1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone injectable progestogen; Contraceptive vaginal ring; percutaneous contraceptive patches. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability as assessed by number of subjects with adverse event (AEs) and serious adverse events (SAEs) | From Day 1 up to Day 105 (For Cohort 5 up to Day 133) | — |
| Safety and tolerability as assessed by composite of clinical laboratory tests: clinical chemistry, hematology and urinalysis | From Day 1 up to Day 105(For Cohort 5 up to Day 133) | Clinical laboratory tests will include clinical chemistry, hematology and urinalysis. |
| Safety and tolerability as assessed by composite of vital signs assessment: blood pressure, heart rate and temperature | From Day 1 up to Day 105 (For Cohort 5 up to Day 133) | Vital signs assessment including systolic and diastolic blood pressure, heart rate and body temperature. |
| Safety as assessed by electrocardiogram (ECG) measurements | From Day 1 up to Day 105 | ECGs will be measured in the semi-supine position. Triplicate 12-lead ECGs will be recorded at screening, Day 1 pre-dose and Day 5 and single 12-lead ECGs at all other time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentrations of GSK2330811 | Samples will be collected at pre-dose, and at 8 hours post dose on Day 1 and single sample on Day 2, Day 3, Day 5, Day 7, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 84, Day 105 and Day 133 | Plasma concentration of GSK2330811 will be determined from blood samples collected at various time points indicated in timeframe. |
| Incidence, specificity and titers of anti-GSK2330811 antibodies | Samples will be collected at pre-dose, Day 14, Day 28 and Day 105. | Serum samples from 4 millilitre (mL) of whole blood will be collected to evaluate incidence, specificity and titers of anti-GSK2330811 antibodies |
| Composite PK parameters including Cmax, AUC, t1/2 and Vss/F after single s.c. doses of GSK2330811 in healthy subjects | Samples will be collected at pre-dose and at 8 hours post dose on Day 1 and single sample on Day 2, Day 3, Day 5, Day 7, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 84, Day 105 and Day 133 | PK parameters will include maximum observed concentration (Cmax), area under concentration-time curve (AUC), terminal phase half-life (t1/2), and Steady State Volume of Distribution / Bioavailability (Vss/F) |
Countries
United Kingdom
Outcome results
None listed