Clinical Trial: Proof of Mechanism Study of GSK2330811 in Diffuse Cutaneous Systemic Sclerosis

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Multi-center, Randomized, Double-blind (Sponsor Open), Placebo-controlled, Repeat-dose, Proof of Mechanism Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Explore

Brief Summary: GSK2330811 is a humanized monoclonal antibody which is in development for systemic sclerosis (SSc), a rare autoimmune disease with high morbidity and mortality. Currently, there are no approved disease modifying therapies and it is an area of high unmet medical need. GSK2330811 has been shown to bind and neutralize Oncostatin M (OSM) that has been associated with fibrosis, vasculopathy and inflammation in a number of diseases. This multi-center, randomized, double-blind (sponsor open), placebo controlled, proof of mechanism study will be the first study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of repeat subcutaneous (SC) doses of GSK2330811 in male and female participants with diffuse cutaneous SSc (dcSSc). Participants with active disease and a disease duration of <= 60 months will be enrolled. Approximately 24 to 40 participants will be randomized across two sequential cohorts. Cohort 1 will evaluate a repeat-dose predicted to provide sub-maximal inhibition of OSM, leading to a dose escalation decision. Cohort 1 is planned to consist of at least 4 participants, randomized such that 3 participants will receive GSK2330811 100 milligram (mg) and 1 will receive placebo. Cohort 2 is planned to consist of at least 20 participants, randomized such that participants will receive GSK2330811 300 mg and placebo in a 3:1 ratio respectively. The duration of the study is up to 34 weeks including a screening period of up to 6 weeks, treatment period of 12 weeks and follow-up period of 16 weeks.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Number of participants with any adverse event (AE) and any serious adverse event (SAE) as a measure of safety and tolerability [ Time Frame: Up to Day 197 ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function.
  • Hematology assessed as a measure of safety and tolerability [ Time Frame: Day 1 (pre-dose), Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 155 and Day 197 ]
    Hematology parameters will be assessed.
  • Clinical chemistry assessed as a measure of safety and tolerability [ Time Frame: Day 1 (pre-dose), Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 155 and Day 197 ]
    Clinical chemistry parameters will be assessed.
  • Urinalysis assessed as a measure of safety and tolerability [ Time Frame: Day 1 (pre-dose), Day 85 and Day 197 ]
    Routine urinalysis parameters will be assessed.
  • Systolic and diastolic blood pressure (BP) as a measure of safety and tolerability [ Time Frame: Day 1 (pre-dose), Day 15 (pre-dose), Day 29 (pre-dose), Day 43 (pre-dose), Day 57 (pre-dose), Day 71 (

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Plasma concentrations of GSK2330811 [ Time Frame: PK samples will be collected at Day 1 (pre-dose), Day 15, Day 29, Day 57, Day 85, Day 113, Day 155 and Day 197 ]
      Blood samples will be collected at indicated time points for PK analysis.
    • Concentration at the end of the dosage interval (Ctrough) of GSK2330811 [ Time Frame: PK samples will be collected at Day 15, Day 29, Day 57, Day 85 ]
      Blood samples will be collected at indicated time points for PK analysis.
    • Apparent clearance (CL/F) of GSK2330811 [ Time Frame: PK samples will be collected at Day 1 (pre-dose), Day 15, Day 29, Day 57, Day 85, Day 113, Day 155 and Day 197 ]
      The CL/F is defined as the apparent total clearance of the drug from plasma. CL/F will be derived from blood samples collected at indicated time points for PK analysis.
    • Apparent volume of distribution (Vss/F) [ Time Frame: PK samples will be collected at Day 1 (pre-dose), Day 15, Day 29, Day 57, Day 85, Day 113, Day 155 and Day 197 ]
      Vss/F is defined as apparent volume of distribution at steady state after non-intravenous administration. Vss/F will be derived from blood samples collected at indicated time points for PK analysis.
    • Serum levels of total OSM [ Time Frame: Blood samples will be collected at Day 1 (pre-dose), Day 15, Day 29, Day 57, Day 85, Day 113, Day 155 and Day 197 ]
      Blood samples will be collected for measurement of serum levels of total OSM protein at indicated time points.
    • Serum levels of free OSM [ Time Frame: Blood samples will be collected at Day 1 (pre-dose), Day 15, Day 29, Day 57, Day 85, Day 113, Day 155 and Day 197 ]
      Blood samples will be collected for measurement of serum levels of free OSM protein at indicated time points.
    • Incidence and titers of anti-GSK2330811 antibodies [ Time Frame: Blood samples will be collected at Day 1 (pre-dose), Day 15, Day 57, Day 85 and Day 197 ]
      Serum samples from whole blood will be collected at indicated time points.


    Original Secondary Outcome: Same as current

    Information By: GlaxoSmithKline

    Dates:
    Date Received: January 31, 2017
    Date Started: May 12, 2017
    Date Completion: December 31, 2018
    Last Updated: May 2, 2017
    Last Verified: May 2017