Characterisation of T-cell Response to Keyhole Limpet Hemocyanin (KLH) and Tuberculin Purified Protein Derivative (PPD)
Condition: Dermatitis
MeSH terms: Dermatitis
Study type: Interventional
Phase: Phase 1

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.
    


Intervention name(s): KLH 0.1 mg; KLH 5 mg; PBS (0.1 mL); Tuberculin PPD
Intervention type(s): Other; Other; Other; Other
Intervention description(s): KLH will be administered as single ID injection of 0.1 mg as 0.1mL of KLH (1 mg/mL); KLH will be administered as single SC injection of 5 mg; 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; 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.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Suction Skin Blister; Induration; Tuberculin Purified Protein Derivative; Erythema; Biopsy; Keyhole Limpet Hemocyanin; Delayed Type Hypersensitivity