Dataset Information

Anti-IL-7 receptor α monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study.

ABSTRACT:

Aim

Interleukin (IL)-7 signalling modulates T cell activity and is implicated in numerous autoimmune diseases. The present study investigated the safety, pharmacokinetics, target engagement, pharmacodynamics and immunogenicity of GSK2618960, an IL-7 receptor-α subunit (CD127) monoclonal antibody.

Methods

A double-blind (sponsor-unblind) study of a single intravenous infusion of either GSK2618960 (0.6 mg kg^-1 or 2.0 mg kg^-1 ) or placebo was carried out in 18 healthy subjects over 24 weeks.

Results

GSK2618960 was well tolerated; there were no serious or significant adverse events. The observed half-life was 5 (±1) days (2.0 mg kg^-1 ), with nonlinear pharmacokinetics. Full receptor occupancy (>95%) was observed until day 8 (0.6 mg kg^-1 ) and day 22 (2.0 mg kg^-1 ). Maximal inhibition of IL-7-mediated signal transducer and activator of transcription 5 (STAT5) phosphorylation was observed in 5/6 subjects until day 22 (2.0 mg kg^-1 ). Mean circulating IL-7 and soluble receptor (CD127) levels were increased above baseline during days 2 and 15 (0.6 mg kg^-1 ) and days 2 and 22 (2.0 mg kg^-1 ). No meaningful changes were observed in absolute numbers or proportions of immune cell populations or inflammatory cytokine profiles (IL-6, tumour necrosis factor-α, interferon-γ, IL-2). Persistent antidrug antibodies (ADAs) were detected in 5/6 subjects administered a dose of 0.6 mg kg^-1 (neutralizing in 2/6) and in 6/6 subjects administered 2.0 mg kg^-1 (neutralizing in 5/6).

Conclusion

GSK2618960 was well tolerated and blocked IL-7 receptor signalling upon full target engagement. Although there was no discernible impact on peripheral T cell subsets in healthy subjects, GSK2618960 may effectively modulate the autoinflammatory activity of pathogenic T cells in diseased tissue. A relatively short half-life is likely the result of target-mediated rather than ADA-mediated clearance.

SUBMITTER: Ellis J

PROVIDER: S-EPMC6339973 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Anti-IL-7 receptor α monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study.

Ellis Joanne J van Maurik Andre A Fortunato Lea L Gisbert Sophie S Chen Keguan K Schwartz Ann A McHugh Simon S Want Andrew A Santos Franco Sara S Oliveira Joao-Joaquim JJ Price Jeffrey J Coles Alasdair A Brown Kim K Su Donggang D Craigen Jenny L JL Yang Jiansong J Brett Sara S Davis Bill B Cheriyan Joseph J Kousin-Ezewu Onajite O Gray Frank F Thompson Paul W PW Fernando Disala D

British journal of clinical pharmacology 20181203 2

<h4>Aim</h4>Interleukin (IL)-7 signalling modulates T cell activity and is implicated in numerous autoimmune diseases. The present study investigated the safety, pharmacokinetics, target engagement, pharmacodynamics and immunogenicity of GSK2618960, an IL-7 receptor-α subunit (CD127) monoclonal antibody.<h4>Methods</h4>A double-blind (sponsor-unblind) study of a single intravenous infusion of either GSK2618960 (0.6 mg kg<sup>-1</sup> or 2.0 mg kg<sup>-1</sup> ) or placebo was carried out in 18 h ...[more]

PMID: 30161291

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Dataset Information

Anti-IL-7 receptor α monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study.

Aim

Methods

Results

Conclusion

Publications

Anti-IL-7 receptor α monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study.

Similar Datasets

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