NCT01480271

An Investigation of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2245035 in Healthy Volunteers and Allergic Rhinitics.

A Randomized, Double-blind, Placebo-controlled First Time Into Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intranasal Dosing With GSK2245035, a TLR7 Agonist, in Healthy Volunteers and Allergic Rhinitics

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 61 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: Male
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

GSK2245035 is a highly selective Toll-like Receptor 7(TLR7) agonist capable of preferentially inducing the production of interferon alpha (IFNα) versus tumor necrosis factor alpha (TNFα). The aim of this FTIH study is to collect tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) information to enable the identification of appropriate safe doses of intranasal (i.n) GSK2245035, associated with up-regulation of TLR7-mediated genes in the nasal milieu, for use in subsequent clinical drug development studies. There will be two parts to the study: Healthy Volunteers will be dosed in escalating single doses in Part 1, followed by Allergic Rhinitis (AR) subjects dosed similarly in Part 2.

Detailed description

This is a First Time in Human (FTIH) study to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single, escalating doses of intranasal (i.n.) GSK2245035 in healthy male volunteers (HVT) and male subjects with allergic rhinitis (AR). The safety and tolerability of single i.n. GSK2245035 dosing will be assessed and established in HVT before the initiation of evaluation in AR. GSK2245035 is a highly selective Toll-like Receptor 7 (TLR7) agonist capable of preferentially inducing the production of IFNα rather than TNFα. Activation of TLR7 is known to result in upregulation of co-stimulatory signals on antigen-presenting cells and in generation of pro-inflammatory mediators that can shift bystander immune responses towards a Helper T-cell Type 1/ Regulatory T cell (Th1/Treg) phenotype and therefore reduce the magnitude of Helper T-cell Type 2 (Th2) reactivity. In this context, it is proposed that i.n. GSK2245035 administration may alter the airways immune environment in a way that results in long-lasting control of AR symptoms and potentially disease remission through persistent modification of the underlying aberrant Th2 responsiveness to aeroallergens. The aim of this study is to collect tolerability, PK and PD information to enable the identification of appropriate safe doses of i.n. GSK2245035, associated with up-regulation of TLR7-mediated genes in the nasal milieu, for use in subsequent clinical drug development studies. The study will be divided in to two parts. Part 1, involving only healthy volunteers, will consist of 8 cohorts receiving doses from 2 nanograms (2 ng) to 4000ng or a placebo dose. Administration within each cohort will be staggered so that two subjects (one receiving drug and one placebo) will be dosed and monitored for 24 hours before any subsequent doses. Screening for part 2 of the study will begin once data from cohort 4 in part 1 has been found to be satisfactory. Part 2 will involve subjects with Allergic Rhinitis and be divided into three cohorts receiving doses between 20ng and 4000ng or a placebo dose.

Conditions

• Rhinitis, Allergic, Seasonal

Interventions

Type	Name	Description
DRUG	2 ng GSK2445053	2ng GSK2445053 administered intranasally
DRUG	20ng GSK2445053	20ng GSK2445053 administered intranasally
DRUG	100ng GSK2445053	100ng GSK2445053 administered intranasally
DRUG	200ng GSK2445053	200ng GSK2445053 administered intranasally
DRUG	400ng GSK2445053	400ng GSK2445053 administered intranasally
DRUG	1000ng GSK2445053	1000ng GSK2445053 administered intranasally
DRUG	2000ng GSK2445053	2000ng GSK2445053 administered intranasally
DRUG	4000ng GSK2445053	4000ng GSK2445053 administered intranasally
DRUG	Placebo	Placebo administered intranasally

Timeline

• Start date: 2011-05-30
• Primary completion: 2011-09-30
• Completion: 2011-09-30
• First posted: 2011-11-28
• Last updated: 2017-06-28

Locations

1 site across 1 country: Netherlands