DermatitisPhase 1NCT01910662
Characterisation of T-cell Response to Keyhole Limpet Hemocyanin (KLH) and Tuberculin Purified Protein Derivative (PPD)
A Phase 1 study testing KLH 0.1 mg, KLH 5 mg and PBS (0.1 mL) in people with Dermatitis, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Dermatitis
- What is being tested?
- KLH 0.1 mg, KLH 5 mg and PBS (0.1 mL)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 22 Feb 2013to 26 Nov 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical Evaluation.
- Body weight >= 50 kg and body mass index (BMI) within the range 19.5 to 29.9 kilogram/meter squared (inclusive).
- Female subjects of non-child bearing potential. Females of child bearing potential are eligible to enter if they are not pregnant and willing to use protocol-specified methods of contraception to prevent pregnancy.
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods from the time of the first dose of challenge agent until follow-up.
- Capable of giving written informed consent.
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- Alanine aminotransferase (ALT) alkaline phosphatase and bilirubin <or=1.5x upper limit of normal (ULN).
- Normal electrocardiogram (ECG) measurements. Average QT duration corrected for heart rate by Fridericia's formula (QTcF) <450 millisecond (msec).
- Part B and C cohort 2 only: Subjects with a history of Bacillus Calmette Guérin (BCG) vaccination as evidence by either a BCG scar and verbal confirmation of BCG vaccination or documented medical history of a BCG vaccination with or without a BCG scar
Who cannot join
- Prior medical history of anaphylaxis, severe adverse reaction to vaccines, allergy to shellfish, asthma (excluding childhood asthma), allergic rhinitis or atopic dermatitis, severe adverse reaction to local anaesthetic, previous tuberculosis infection.
- Current treatment with beta-blockers or angiotensin converting enzyme (ACE) inhibitors.
- History of sensitivity to any of the study challenge agents or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.
- Received live, attenuated or recombinant vaccine(s) within 2 months of the first KLH or PPD injection or will require vaccination prior to the follow-up visit.
- Part B and C cohort 2 only: From a high risk area of the world for tuberculosis or have close family members with confirmed Mycobacterium tuberculosis (MTB).
- Antibiotics or antiviral therapy after a serious illness within 30 days of study entry.
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- Immunodeficiency or autoimmunity, assessed by medical history.
- Presence of tattoos, naevi or other skin abnormalities such as keloids (or history of keloids) that may, in the opinion of the investigator, interfere with study assessments.
- Use of nicotine patches on the arm at screening that would interfere with the injection sites.
- Subjects participating, within 7 days of screening, in recreational sun-bathing, or use of sun-bed, on the area of the skin from wrist to shoulder inclusive.
- The subject has a phobia to needles or minor surgical procedures.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of regular alcohol consumption within 6 months of the study.
- Use of prescription drugs or non-prescription drugs, including NSAIDs, if in the opinion of the Investigator the medication will interfere with the study procedures or compromise subject safety. Subjects must not currently take any of the following: topical steroid cream on the arms, oral or systemic steroids or any other immune-modulators.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency virus (HIV) antibody.
- Pregnant or lactating females.
- Donation of more than 500 milliliter (mL) blood within a 56 day period.
- Participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Part A and part B Cohort 1: The subject has received KLH SC or ID in the past.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Characterisation of the T-cell Response in Delayed Type Hypersensitivity Reactions to Keyhole Limpet Hemocyanin (KLH) and Tuberculin Purified Protein Derivative (PPD) in Healthy Volunteers
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
- Being tested
- KLH 0.1 mg, KLH 5 mg, PBS (0.1 mL), Tuberculin PPD
- Keywords
- Suction Skin Blister, Induration, Tuberculin Purified Protein Derivative, Erythema, Biopsy, Keyhole Limpet Hemocyanin, Delayed Type Hypersensitivity
- Medical subject headings
- Dermatitis, Erythema, Hypersensitivity, Delayed
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KLH 0.1 mgOther
KLH will be administered as single ID injection of 0.1 mg as 0.1mL of KLH (1 mg/mL)
KLH 5 mgOther
KLH will be administered as single SC injection of 5 mg
PBS (0.1 mL)Other
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 PPDOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Part A: | Experimental | Subjects in the Part A will receive an ID injection of 0.1 mg KLH as 0.1 mL of KLH (1 mg/mL) in the upper right forearm and an ID injection of 0.1 mL of buffer in the lower right forearm and lower and upper left forearm on Day 1. Receives: Other: KLH 0.1 mg; Other: PBS (0.1 mL) |
| Part B:Cohort 1A | Experimental | Subjects in the Part B Cohort 1A arm will receive a SC immunisation of 5 mg KLH in the right deltoid. On Day 15 subjects will return to the unit for an ID injection of 0.1 mg KLH as 0.1 mL of KLH (1 mg/mL) in the lower right and lower left forearm. On Day 43, 0.1mL of KLH (1 mg/mL) will be injected ID into the upper left forearm and the upper right forearm (The dose can be changed to either 5mg/1mg or 1mg/0.1mg depending on the results from the first 3 subjects in Cohort 1). Receives: Other: KLH 0.1 mg; Other: KLH 5 mg |
| Part B:Cohort 1B | Experimental | Subjects in the Part B Cohort 1B arm will receive a SC immunisation of 5 mg KLH in the right deltoid on Day 1. On Day 15 subjects will return to the unit for an ID injection of 0.1 mg KLH in the lower right and lower left forearm. On Day 43 subjects will then receive an ID injection of 0.1 mg KLH in the upper right and upper left forearms (The dose can be changed to either 5mg/1mg or 1mg/0.1mg depending on the results from the first 3 subjects in Cohort 1). Receives: Other: KLH 0.1 mg; Other: KLH 5 mg |
| Part B:Cohort 2 | Experimental | Subjects in the Part B Cohort 2 will receive an ID injection of 2TU (0.04 microg/mL) PPD in the upper right and upper left forearms on Day 1. On Day 3 (48 hours post challenge) If the induration is less than 6 mm, the subject will be re-challenged with 10 TU (0.04 microg/mL) PPD at a site at least 4 cm away from another challenge site. On Day 29 the subjects will have 2 ID injections of 2 TU or 10 TU (the same dose that produced an induration of 6 mm or more). Receives: Other: Tuberculin PPD |
| Part C: Cohort 1 | Experimental | Subjects in the Part C Cohort 1 will receive an ID injection of 0.1 mL PBS in the upper right forearm on Day 1. On Day 2 subjects will receive an ID injection of 0.1 ml PBS in the upper left forearm. Receives: Other: PBS (0.1 mL) |
| Part C: Cohort 2 | Experimental | Subjects in the Part C Cohort 2 will receive an ID injection of 2TU (0.04 microg/mL) PPD in the upper left forearms on Day 1. On Day 3 (48 hours post challenge) If the induration is less than 6 mm, the subject will be re-challenged with 10 TU (0.04 microg/mL) PPD at a site at least 4 cm away from another challenge site. On Day 29 the subjects will have 1 ID injections of 2 TU or 10 TU (the same dose that produced an induration of 6 mm or more). Receives: Other: Tuberculin PPD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Skin inflammatory response measurement as induration by the ball point pen technique
The induration of wheals (defined as elevation and induration that are palpable in the skin) that develop as a result of intradermal immunisation with KLH or PPD will be measured in the vertical and horizontal plane using the ball point pen technique. The diameter of the induration will be measured by rolling a medium ball point pen from 10 to 20 millimetre (mm) outside the edge of the induration and toward the centre with just enough pressure to indent the skin slightly.
Measured: Over a four day period after challenge
Part A: Skin inflammatory response measurement as erythema diameter by Laser Doppler Imaging (LDI) and ruler measurement
A Laser Doppler Imager will measure the area occupied by a given wheal and associated erythema, which reflects superficial blood flow of a subject's arm. Erythema at the immunisation site will be measured in the vertical and horizontal plane using a plastic flexible mm ruler. Measurements will be taken for both challenge agent and buffer control injections. Place the zero line of the ruler just inside the left edge of the area of erythema and read the ruler line just inside the right edge.
Measured: Over a four day period after challenge
Part A: Skin inflammatory response measurement as induration by characterisation and measurement of the T-cells in skin biopsies
T-cells will be analysed by immunocytochemistry or other techniques to characterise the T-cells
Measured: Over a three day period after challenge
Part B: Characterisation of T-cells in a skin DTH response
Lymphocyte Activation Gene 3 (LAG 3+) T-cells collected by Punch Biopsy or skin blister will be characterised and measured by Fluorescence activated cell sorter (FACS) analysis or other immunologic techniques
Measured: Cohort 1: Over a five day period after first challenge. Cohort 2: Over a five day period after first challenge
Part C: Characterisation of T-cells in a skin DTH response
Lymphocyte Activation Gene 3 (LAG 3+) T-cells collected by skin blister will be characterised and measured by Fluorescence activated cell sorter (FACS) analysis or other immunologic techniques
Measured: Cohort 1: Over a five day period after first challenge. Cohort 2: Over a three day period after first challenge
Secondary outcomes (22)
Part A: Characterisation and measurement of the T-cells in skin biopsies.
T-cells will be analysed by immunocytochemistry or other techniques to characterise the T-cells
Measured: At 48hrs (Day 3) after challenge
Part B: Skin inflammatory response measurement in Cohort 1 by the ball point pen technique
The induration of wheals (defined as elevation and induration that are palpable in the skin) that develop as a result of intradermal immunisation with KLH or PPD will be measured in the vertical and horizontal plane using the ball point pen technique. The diameter of the induration will be measured by rolling a medium ball point pen from 10 to 20 mm outside the edge of the induration and toward the centre with just enough pressure to indent the skin slightly.
Measured: Cohort 1A: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At Day 44 and 48hrs (Day 45) after second challenge. Cohort 1B: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At Day 44, 45 and 120hrs (Day 48) after second challenge
Part B: Skin inflammatory response measurement in Cohort 2 by the ball point pen technique
The induration of wheals (defined as elevation and induration that are palpable in the skin) that develop as a result of intradermal immunisation with KLH or PPD will be measured in the vertical and horizontal plane using the ball point pen technique. The diameter of the induration will be measured by rolling a medium ball point pen from 10 to 20 mm outside the edge of the induration and toward the centre with just enough pressure to indent the skin slightly.
Measured: Cohort 2: At 48hrs (Day3) and 120hrs (Day 6) after first challenge. At 48hrs (Day 31) and 120hrs (Day 34) after second challenge.
Part B: Erythema diameter measured in Cohort 1 by Laser Doppler Imaging (LDI) and ruler measurement.
A Laser Doppler Imager will measure the area occupied by a given wheal and associated erythema, which reflects superficial blood flow of a subject's arm.
Measured: Cohort 1A: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At Day 44 and 48hrs (Day 45) after second challenge. Cohort 1B: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At Day 44, 45 and 120hrs (Day 48) after second challenge
Part B: Erythema diameter measured in Cohort 2 by Laser Doppler Imaging (LDI) and ruler measurement.
A Laser Doppler Imager will measure the area occupied by a given wheal and associated erythema, which reflects superficial blood flow of a subject's arm.
Measured: Cohort 2: At 48hrs (Day3) and 120hrs (Day 6) after first challenge. At 48hrs (Day 31) and 120hrs (Day 34) after second challenge.
Part B: Characterisation and measurement of the T-cells in skin biopsies in Cohort 1.
T-cells will be analysed by immunocytochemistry or other techniques to characterise the T-cells
Measured: Cohort 1A: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At 48hrs (Day 45) after second challenge. Cohort 1B: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At 120hrs (Day 48) after second challenge.
Part B: Characterisation and measurement of the T-cells in skin biopsies in Cohort 2.
T-cells will be analysed by immunocytochemistry or other techniques to characterise the T-cells
Measured: Cohort 2: At 48hrs (Day3) and 120hrs (Day 6) after first challenge. At 48hrs (Day 31) and 120hrs (Day 34) after second challenge.
Part A and B: Number of subjects with adverse events as a measure of safety and tolerability
The safety and tolerability of skin challenges with KLH and PPD.administration will be assessed by adverse events (AEs), serious AE (SAE) or withdrawals due to toxicities
Measured: Part A: Day 1 to Day 4, Part B: Cohort 1A: Day 1 to Day 46.Part B: Cohort 1B:Day 1 to Day 49.Part B Cohort 2: Day 1 to 35.
Part A and B: changes in clinical laboratory measurements to access safety and tolerability
Measured: Screening and up to 14 days post last visit
Part A and B: Trends in and change from baseline for blood pressure measurements
Measured: Screening and up to 14 days post last visit
Trends in and change from baseline in measure of 12-lead ECG to access safety and tolerability
Electrocardiograph (ECG) is a machine that measures the electrical activity of the heart and records changes in the hearts' rhythm.
Measured: Screening and up to 14 days post last visit
Immediate local hypersensitivity assessment
Examination of injection site for evidence of immediate local hypersensitivity/wheal (erythema or induration will not be taken into consideration). The diameter of the wheal (central swelling/raised skin) at immunisation site, if present at time of hypersensitivity assessment, will be measured in vertical and horizontal plane using a millimetre (mm) ruler. The average will be the diameter value. If wheal is more than 5 mm in diameter than original bleb, then subject will be labelled as having immediate local hypersensitivity (ILH) and will undergo both serum total IgE and KLH or PPD prick tes
Measured: 15-30 minutes after each SC and ID challenge immunization in each Study part/Cohort
Part A and B: Trends in and change from baseline for heart rate measurements
Measured: Screening and up to 14 days post last visit
Part C: Skin inflammatory response measurement in Cohort 2 by the ball point pen technique.
The induration of wheals (defined as elevation and induration that are palpable in the skin) that develop as a result of intradermal immunisation with PPD will be measured in the vertical and horizontal plane using the ball point pen technique. The diameter of the induration will be measured by rolling a medium ball point pen from 10 to 20 mm outside the edge of the induration and toward the centre with just enough pressure to indent the skin slightly.
Measured: Cohort 2: At 48hrs (Day3) and 744hrs (Day 31).
Part C: Erythema diameter measured in Cohort 2 by Laser Doppler Imaging (LDI) and ruler measurement.
A Laser Doppler Imager will measure the area occupied by a given wheal and associated erythema, which reflects superficial blood flow of a subject's arm.
Measured: Cohort 2: At pre-challenge (Day1) and 48hrs (Day 3) after first challenge. At pre-challenge (Day 29) and 48hrs (Day 31) after second challenge.
Part C: Characterisation and measurement of the T-cells in skin blisters in Cohort 2.
T-cells will be analysed by immunocytochemistry or other techniques to characterise the T-cells
Measured: Cohort 2: At 48hrs (Day3) and 72hrs (Day 4) after first challenge. At 48hrs (Day 31) and 69hrs (Day 32) after second challenge.
Part A , B and C: Number of subjects with adverse events as a measure of safety and tolerability
The safety and tolerability of skin challenges with KLH and PPD .administration will be assessed by adverse events (AEs), serious AE (SAE) or withdrawals due to toxicities
Measured: Part A: Day 1 to Day 4, Part B: Cohort 1A: Day 1 to Day 46.Part B: Cohort 1B:Day 1 to Day 49.Part B Cohort 2: Day 1 to 35. Part C: Cohort 1:Day 1 to Day 19. Part C Cohort 2: Day 1 to 46.
Part A, B and C: changes in clinical laboratory measurements to access safety and tolerability
Measured: Part A and B: Screening and up to 14 days post last visit. Part C: Screening and up to 14 days post last blister draw.
Part A and B: Screening and up to 14 days post last visit. Part C: Screening and up to 14 days post last blister draw.
Measured: Part A and B: Screening and up to 14 days post last visit. Part C: Screening and up to 14 days post last blister draw.
Trends in and change from baseline in measure of 12-lead ECG to access safety and tolerability
Electrocardiograph (ECG) is a machine that measures the electrical activity of the heart and records changes in the hearts' rhythm.
Measured: Part A and B: Screening and up to 14 days post last visit. Part C: Screening and up to 14 days post last blister draw.
Immediate local hypersensitivity assessments
Examination of injection site for evidence of immediate local hypersensitivity/wheal (erythema or induration will not be taken into consideration). The diameter of the wheal (central swelling/raised skin) at immunisation site, if present at time of hypersensitivity assessment, will be measured in vertical and horizontal plane using a millimetre (mm) ruler. The average will be the diameter value. If wheal is more than 5 mm in diameter than original bleb, then subject will be labelled as having immediate local hypersensitivity (ILH) and will undergo both serum total IgE and KLH or PPD prick tes
Measured: Part A and B: 15-30 minutes after each SC and ID challenge immunization in each Study part/Cohort. Part C: Screening and up to 14 days post last blister draw.
Part A and B: Trends in and change from baseline for heart rate measurement
Measured: Part A and B: Screening and up to 14 days post last visit. Part C: Screening and up to 14 days post last blister draw.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2013 (estimated)
- Study start22 Feb 2013
- Primary completion26 Nov 2013
- Study completion26 Nov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DermatitisStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01910662
- Sponsor's protocol ID
- 117249
- Status last verified
- May 2017
- First submitted
- 14 Feb 2013
- Last updated
- 15 May 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterisation of the T-cell Response in Delayed Type Hypersensitivity Reactions to Keyhole Limpet Hemocyanin (KLH) and Tuberculin Purified Protein Derivative (PPD) in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01910662
- Acronym / sponsor ID
- 117249
- Conditions
- Dermatitis
- Keywords
- Suction Skin Blister, Induration, Tuberculin Purified Protein Derivative, Erythema, Biopsy, Keyhole Limpet Hemocyanin, Delayed Type Hypersensitivity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 22 Feb 2013 (actual)
- Primary completion
- 26 Nov 2013 (actual)
- Study completion
- 26 Nov 2013 (actual)
- First posted
- 29 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part A: | Experimental | Other: KLH 0.1 mg, Other: PBS (0.1 mL)Subjects in the Part A will receive an ID injection of 0.1 mg KLH as 0.1 mL of KLH (1 mg/mL) in the upper right forearm and an ID injection of 0.1 mL of buffer in the lower right forearm and lower and upper left forearm on Day 1. |
| Part B:Cohort 1A | Experimental | Other: KLH 0.1 mg, Other: KLH 5 mgSubjects in the Part B Cohort 1A arm will receive a SC immunisation of 5 mg KLH in the right deltoid. On Day 15 subjects will return to the unit for an ID injection of 0.1 mg KLH as 0.1 mL of KLH (1 mg/mL) in the lower right and lower left forearm. On Day 43, 0.1mL of KLH (1 mg/mL) will be injected ID into the upper left forearm and the upper right forearm (The dose can be changed to either 5mg/1mg or 1mg/0.1mg depending on the results from the first 3 subjects in Cohort 1). |
| Part B:Cohort 1B | Experimental | Other: KLH 0.1 mg, Other: KLH 5 mgSubjects in the Part B Cohort 1B arm will receive a SC immunisation of 5 mg KLH in the right deltoid on Day 1. On Day 15 subjects will return to the unit for an ID injection of 0.1 mg KLH in the lower right and lower left forearm. On Day 43 subjects will then receive an ID injection of 0.1 mg KLH in the upper right and upper left forearms (The dose can be changed to either 5mg/1mg or 1mg/0.1mg depending on the results from the first 3 subjects in Cohort 1). |
| Part B:Cohort 2 | Experimental | Other: Tuberculin PPDSubjects in the Part B Cohort 2 will receive an ID injection of 2TU (0.04 microg/mL) PPD in the upper right and upper left forearms on Day 1. On Day 3 (48 hours post challenge) If the induration is less than 6 mm, the subject will be re-challenged with 10 TU (0.04 microg/mL) PPD at a site at least 4 cm away from another challenge site. On Day 29 the subjects will have 2 ID injections of 2 TU or 10 TU (the same dose that produced an induration of 6 mm or more). |
| Part C: Cohort 1 | Experimental | Other: PBS (0.1 mL)Subjects in the Part C Cohort 1 will receive an ID injection of 0.1 mL PBS in the upper right forearm on Day 1. On Day 2 subjects will receive an ID injection of 0.1 ml PBS in the upper left forearm. |
| Part C: Cohort 2 | Experimental | Other: Tuberculin PPDSubjects in the Part C Cohort 2 will receive an ID injection of 2TU (0.04 microg/mL) PPD in the upper left forearms on Day 1. On Day 3 (48 hours post challenge) If the induration is less than 6 mm, the subject will be re-challenged with 10 TU (0.04 microg/mL) PPD at a site at least 4 cm away from another challenge site. On Day 29 the subjects will have 1 ID injections of 2 TU or 10 TU (the same dose that produced an induration of 6 mm or more). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical Evaluation.
- Body weight >= 50 kg and body mass index (BMI) within the range 19.5 to 29.9 kilogram/meter squared (inclusive).
- Female subjects of non-child bearing potential. Females of child bearing potential are eligible to enter if they are not pregnant and willing to use protocol-specified methods of contraception to prevent pregnancy.
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods from the time of the first dose of challenge agent until follow-up.
Key exclusion criteria (22 listed)
- Prior medical history of anaphylaxis, severe adverse reaction to vaccines, allergy to shellfish, asthma (excluding childhood asthma), allergic rhinitis or atopic dermatitis, severe adverse reaction to local anaesthetic, previous tuberculosis infection.
- Current treatment with beta-blockers or angiotensin converting enzyme (ACE) inhibitors.
- History of sensitivity to any of the study challenge agents or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.
- Received live, attenuated or recombinant vaccine(s) within 2 months of the first KLH or PPD injection or will require vaccination prior to the follow-up visit.
- Part B and C cohort 2 only: From a high risk area of the world for tuberculosis or have close family members with confirmed Mycobacterium tuberculosis (MTB).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KLH 0.1 mgKLH will be administered as single ID injection of 0.1 mg as 0.1mL of KLH (1 mg/mL) | Other | Part A:, Part B:Cohort 1A, Part B:Cohort 1B |
| KLH 5 mgKLH will be administered as single SC injection of 5 mg | Other | Part B:Cohort 1A, Part B:Cohort 1B |
| 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 | Part A:, Part C: Cohort 1 |
| Tuberculin PPDTuberculin 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. | Other | Part B:Cohort 2, Part C: Cohort 2 |
Primary outcome
Part A: Skin inflammatory response measurement as induration by the ball point pen technique
Time frame: Over a four day period after challenge
The induration of wheals (defined as elevation and induration that are palpable in the skin) that develop as a result of intradermal immunisation with KLH or PPD will be measured in the vertical and horizontal plane using the ball point pen technique. The diameter of the induration will be measured by rolling a medium ball point pen from 10 to 20 millimetre (mm) outside the edge of the induration and toward the centre with just enough pressure to indent the skin slightly.
Part A: Skin inflammatory response measurement as erythema diameter by Laser Doppler Imaging (LDI) and ruler measurement
Time frame: Over a four day period after challenge
A Laser Doppler Imager will measure the area occupied by a given wheal and associated erythema, which reflects superficial blood flow of a subject's arm. Erythema at the immunisation site will be measured in the vertical and horizontal plane using a plastic flexible mm ruler. Measurements will be taken for both challenge agent and buffer control injections. Place the zero line of the ruler just inside the left edge of the area of erythema and read the ruler line just inside the right edge.
Part A: Skin inflammatory response measurement as induration by characterisation and measurement of the T-cells in skin biopsies
Time frame: Over a three day period after challenge
T-cells will be analysed by immunocytochemistry or other techniques to characterise the T-cells
Part B: Characterisation of T-cells in a skin DTH response
Time frame: Cohort 1: Over a five day period after first challenge. Cohort 2: Over a five day period after first challenge
Lymphocyte Activation Gene 3 (LAG 3+) T-cells collected by Punch Biopsy or skin blister will be characterised and measured by Fluorescence activated cell sorter (FACS) analysis or other immunologic techniques
Part C: Characterisation of T-cells in a skin DTH response
Time frame: Cohort 1: Over a five day period after first challenge. Cohort 2: Over a three day period after first challenge
Lymphocyte Activation Gene 3 (LAG 3+) T-cells collected by skin blister will be characterised and measured by Fluorescence activated cell sorter (FACS) analysis or other immunologic techniques
22 secondary outcomes
Part A: Characterisation and measurement of the T-cells in skin biopsies.
Time frame: At 48hrs (Day 3) after challenge
Part B: Skin inflammatory response measurement in Cohort 1 by the ball point pen technique
Time frame: Cohort 1A: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At Day 44 and 48hrs (Day 45) after second challenge. Cohort 1B: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At Day 44, 45 and 120hrs (Day 48) after second challenge
Part B: Skin inflammatory response measurement in Cohort 2 by the ball point pen technique
Time frame: Cohort 2: At 48hrs (Day3) and 120hrs (Day 6) after first challenge. At 48hrs (Day 31) and 120hrs (Day 34) after second challenge.
Part B: Erythema diameter measured in Cohort 1 by Laser Doppler Imaging (LDI) and ruler measurement.
Time frame: Cohort 1A: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At Day 44 and 48hrs (Day 45) after second challenge. Cohort 1B: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At Day 44, 45 and 120hrs (Day 48) after second challenge
Part B: Erythema diameter measured in Cohort 2 by Laser Doppler Imaging (LDI) and ruler measurement.
Time frame: Cohort 2: At 48hrs (Day3) and 120hrs (Day 6) after first challenge. At 48hrs (Day 31) and 120hrs (Day 34) after second challenge.
Part B: Characterisation and measurement of the T-cells in skin biopsies in Cohort 1.
Time frame: Cohort 1A: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At 48hrs (Day 45) after second challenge. Cohort 1B: At 48hrs (Day 17) and 120hrs (Day 20) after first challenge. At 120hrs (Day 48) after second challenge.
Part B: Characterisation and measurement of the T-cells in skin biopsies in Cohort 2.
Time frame: Cohort 2: At 48hrs (Day3) and 120hrs (Day 6) after first challenge. At 48hrs (Day 31) and 120hrs (Day 34) after second challenge.
Part A and B: Number of subjects with adverse events as a measure of safety and tolerability
Time frame: Part A: Day 1 to Day 4, Part B: Cohort 1A: Day 1 to Day 46.Part B: Cohort 1B:Day 1 to Day 49.Part B Cohort 2: Day 1 to 35.
Part A and B: changes in clinical laboratory measurements to access safety and tolerability
Time frame: Screening and up to 14 days post last visit
Part A and B: Trends in and change from baseline for blood pressure measurements
Time frame: Screening and up to 14 days post last visit
Trends in and change from baseline in measure of 12-lead ECG to access safety and tolerability
Time frame: Screening and up to 14 days post last visit
Immediate local hypersensitivity assessment
Time frame: 15-30 minutes after each SC and ID challenge immunization in each Study part/Cohort
Part A and B: Trends in and change from baseline for heart rate measurements
Time frame: Screening and up to 14 days post last visit
Part C: Skin inflammatory response measurement in Cohort 2 by the ball point pen technique.
Time frame: Cohort 2: At 48hrs (Day3) and 744hrs (Day 31).
Part C: Erythema diameter measured in Cohort 2 by Laser Doppler Imaging (LDI) and ruler measurement.
Time frame: Cohort 2: At pre-challenge (Day1) and 48hrs (Day 3) after first challenge. At pre-challenge (Day 29) and 48hrs (Day 31) after second challenge.
Part C: Characterisation and measurement of the T-cells in skin blisters in Cohort 2.
Time frame: Cohort 2: At 48hrs (Day3) and 72hrs (Day 4) after first challenge. At 48hrs (Day 31) and 69hrs (Day 32) after second challenge.
Part A , B and C: Number of subjects with adverse events as a measure of safety and tolerability
Time frame: Part A: Day 1 to Day 4, Part B: Cohort 1A: Day 1 to Day 46.Part B: Cohort 1B:Day 1 to Day 49.Part B Cohort 2: Day 1 to 35. Part C: Cohort 1:Day 1 to Day 19. Part C Cohort 2: Day 1 to 46.
Part A, B and C: changes in clinical laboratory measurements to access safety and tolerability
Time frame: Part A and B: Screening and up to 14 days post last visit. Part C: Screening and up to 14 days post last blister draw.
Part A and B: Screening and up to 14 days post last visit. Part C: Screening and up to 14 days post last blister draw.
Time frame: Part A and B: Screening and up to 14 days post last visit. Part C: Screening and up to 14 days post last blister draw.
Trends in and change from baseline in measure of 12-lead ECG to access safety and tolerability
Time frame: Part A and B: Screening and up to 14 days post last visit. Part C: Screening and up to 14 days post last blister draw.
Immediate local hypersensitivity assessments
Time frame: Part A and B: 15-30 minutes after each SC and ID challenge immunization in each Study part/Cohort. Part C: Screening and up to 14 days post last blister draw.
Part A and B: Trends in and change from baseline for heart rate measurement
Time frame: Part A and B: Screening and up to 14 days post last visit. Part C: Screening and up to 14 days post last blister draw.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2017.
- Results for study 117249 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KLH 0.1 mg, KLH 5 mg and PBS (0.1 mL) in people with Dermatitis, run by GlaxoSmithKline at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Skin inflammatory response measurement as induration by the ball point pen technique (time frame: Over a four day period after challenge). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.