Clinical Trial: Safety Escalating Repeat IV, in Stroke Patients

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Single-Blind Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Repeat Doses of GSK249320 in Patients With Stroke

Brief Summary: The purpose of this study is to is to test increasing repeat doses of GSK249320 compared to placebo in patients with stroke.

Detailed Summary: GSK249320 is a humanised monoclonal antibody (mAb) that binds with high specificity to myelin-associated glycoprotein (MAG) and antagonises or neutralises MAG-mediated inhibition and has been shown to improve functional recovery after stroke in pre-clinical models, possibly by promoting neuroregeneration and plasticity. The present study is the first in patients with stroke. The main aim of this study is to select tolerated doses of GSK249320 that can be used in future trials to evaluate its efficacy in improving clinical function in patients recovering from stroke. This clinical trial is designed as a placebo-controlled, single-blind, multicenter study to investigate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of escalating repeat IV doses of GSK249320. Three sequential dose escalation cohorts (1, 5 and 15 mg/kg) are planned, with 8 patients on placebo and 8 on active in cohort 1 and 4 patients on placebo and 8 on active in cohorts 2 and 3. Each patient will receive 2 repeat IV doses 9 ± 1 days apart and assessments will extend to at least 16 weeks.
Sponsor: GlaxoSmithKline

Current Primary Outcome: Adverse events (AEs), vital signs, physical examination (incl. full neurological exam.), 12-lead ECGs, nerve conduction tests (NCTs), magnetic resonance imaging (MRI) and clinical laboratory tests [ Time Frame: 16 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Presence of antibodies to GSK249320 will be assessed in serum samples using immunoelectro-chemiluminescent (ECL) assay [ Time Frame: At least 16 weeks ]
  • PK parameters: AUC(0-), Cmax, Tmax, T1/2 after second dose, clearance, volume of distribution [ Time Frame: At least 16 weeks ]
  • Gait velocity, Berg Balance, Fugl-Meyer Motor Assessment, Box and Blocks, grip strength (dynamometer), modified Rankin, Barthel, NIHSS, Transcranial Magnetic Stimulation (TMS), and MRI [ Time Frame: At least 16 weeks ]
  • To explore linear or non-linear relationships between exposure parameters and one or a combination of PD endpoints. Possible extension to a disease progression model, if feasible [ Time Frame: At least 16 weeks ]
  • Exploratory biomarker levels, such as S100β [ Time Frame: At least 16 weeks ]


Original Secondary Outcome: Presence of antibodies to GSK249320 will be assessed in serum samples using immunoelectro-chemiluminescent (ECL) assay [ Time Frame: At least 16 weeks ]

Information By: GlaxoSmithKline

Dates:
Date Received: January 29, 2009
Date Started: July 2009
Date Completion:
Last Updated: November 29, 2016
Last Verified: November 2016