Characterisation of T-cell Response to Keyhole Limpet Hemocyanin (KLH) and Tuberculin Purified Protein Derivative (PPD)

Summary

This is an exploratory study to develop methodologies for the assessment of T-cell mediated therapies via skin immune challenges studies in healthy volunteers. The study will investigate what is the most appropriate; skin challenge agent, time and methodology to sample and characterise T-cells in the delayed type hypersensitivity (DTH) skin reaction. The skin challenge agents to be used in this study will be the neoantigen Keyhole Limpet Hemocyanin (KLH) and recall antigen Tuberculin Purified Protein Derivative (PPD). Part A of the study will assess an intradermal (ID) KLH challenge in three subjects to assess if the immune response to KLH is initiated by the innate or adaptive immune system. Each subject will receive one ID dose of 0.1 milligram (mg) KLH and will be assessed for a skin inflammatory response. Part B of the study will assess repeat ID challenges 28 days apart; the objective will be to characterise the T-cell response to each challenge and the kinetics of that response.

For Cohorts 1A and 1B, 16 subjects will receive an initial subcutaneous (SC) 5 mg dose of KLH. Fifteen days later the subjects will receive 0.1 mg ID KLH dose and the response will then be assessed 48 and 120 hours after the initial challenge. The ID KLH challenge will then be repeated 28 days later and the response will be assessed at 48 hours (Cohort 1A, 8 subjects) and at 120 hours (Cohort 1B, 8 subjects) post challenge. For Cohort 2, a repeat challenge of either 2 tuberculin Unit (TU) or 10 TU ID PPD will be administered 28 days apart, to 8 subjects. The first challenge response will be assessed 48 and 120 hours post challenge. The second challenge will be administered 28 days after the first and will be assessed at the same timepoints. The repeat challenge 28 days later will allow an intra-subject analysis and will determine if a subject can be used as their own control. Part C of the study will assess repeat ID challenges of PPD and PBS; the objective will be to characterise the T-cell response to each challenge and the kinetics of that response. For Cohort 1, 6 subjects will receive a 0.1ml ID dose of PBS and another dose 24 hours later. Each challenge will be assessed 48 hours post challenge. Approximately 2 subjects will have an assessment of their normal skin as a control. For Cohort 2, a repeat challenge of either 2TU or 10TU ID PPD will be administered 28 days apart, to 6 subjects. The first challenge response will be assessed 48 post challenge. The second challenge will be administered 28 days after the 1st and will be assessed at the same timepoint. The repeat challenge 28 days later will allow an intra-subject analysis and will determine if a subject can be used as their own control.

The total duration of this study for Part A is 14-18 days plus up to 30 days screening. The total duration of this study for Cohort 1A is 56-60 days plus up to 30 days screening. The total duration of this study for Cohort 1B is 59-63 days plus up to 30 days screening. The total duration of this study for Cohort 2 if 2TU is used is 45-49 days plus up to 30 day screening. The total duration of this study for Cohort 2 if 10TU is used is 48-51 days plus up to 30 days screening. The total duration of this study for Part C Cohort 1 is 15-19 days plus up to 30 day screening. The total duration of this study for Cohort 2 if 2TU is used is 42-46 days plus up to 30 day screening. The total duration of this study for Cohort 2 if 10TU is used is 45-49 days plus up to 30 days screening.

Conditions

• Dermatitis

Interventions

OTHER

KLH 0.1 mg

KLH will be administered as single ID injection of 0.1 mg as 0.1mL of KLH (1 mg/mL)

OTHER

KLH 5 mg

KLH will be administered as single SC injection of 5 mg

OTHER

PBS (0.1 mL)

PBS will be administered in Part A on Day 1 as 3 ID injections and in Part C: Cohort 1 on Day 1 and Day 2 as a single ID injection

OTHER

Tuberculin PPD

Tuberculin PPD will be administered in Part B Cohort 2 on Day 1 as single ID injection of 2TU (0.04 microg/mL) in each forearm. In Part C Cohort 2 PPD will be administered on Day 1 as a single ID injection of 2TU. On day 3, if the induration is 6 mm or more; 2 ID injections of 2 TU will be administered on Day 29 in Part B Cohort 2 and 1injection of 2TU on Day 29 in Part C Cohort 2. On day 3, if the induration is less than 6 mm, subject will be re-challenged with 10 TU (0.04 microg/mL) PPD followed by 2 ID injections of 10 TU on Day 29 in Part B Cohort 2 or 1 ID injection of 10TU on Day 29 in Part C Cohort 2.

Sponsors & Collaborators

• GlaxoSmithKline

  lead INDUSTRY

Principal Investigators

• GSK Clinical Trials · GlaxoSmithKline

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-02-22

Primary Completion

2013-11-26

Completion

2013-11-26

Countries

• United Kingdom

Study Locations