KLH Challenge to Explore the Human Immune Response
Varying Keyhole Limpet Haemocyanin-adjuvant Dose Combinations to Explore the Immune Response: a Human Challenge Study
1 other identifier
interventional
39
1 country
1
Brief Summary
One approach to improve the efficiency of the drug development process is the use of human 'immune challenge' studies. In these studies, healthy volunteers are given small amounts of substances which are foreign to their immune system to provoke a temporary response: the 'challenge'. Depending on the nature and dose of the challenge, the body's immune system will react in a different but predictable way, elements of which mimic those seen in disease, thereby 'modelling' them. These models can help safely bridge the gap between animal experiments and patient groups and, if sufficiently understood, test the effect of new drugs without exposing patients to risk. Sadly, whilst immune challenge models have been used in drug development for many years, this has been done in a largely non-standardised, ad hoc manner, which greatly limits the usefulness of the approach. The purpose of this research is to better understand, improve, and standardise a common method of immune challenge which uses a protein called 'Keyhole Limpet Haemocyanin' (KLH). KLH is available as a highly-purified formulation, and because it is not usually encountered by the human immune system (it is derived from an inedible shellfish), it allows us to study the development of immune responses right from the time it is administered. We plan to give different groups of healthy volunteers different doses of KLH with or without an 'immune-boosting' agent (Alhydrogel™ or Montanide ISA™51, commonly referred to as adjuvants), before measuring and comparing their response. We will then re-challenge all the volunteers a month later by injecting different doses of KLH into the skin on their forearms, similar to an allergy test, taking images, blood samples and skin biopsies to understand the nature, time course, and variability of the immune response in each individual. No previous studies have directly explored the effects of KLH dose or adjuvants in a rigorous manner. The results will help us to determine both whether administering KLH with different adjuvants elicits qualitatively different immune response profiles (thus modelling different diseases) and the optimal doses of KLH to evaluate new drugs with. In turn, we hope this will help improve the percentage of drugs progressing from concept to clinical therapy, addressing unmet health needs.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Mar 2023
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2023
CompletedFirst Submitted
Initial submission to the registry
March 17, 2023
CompletedFirst Posted
Study publicly available on registry
May 25, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2024
CompletedMay 25, 2023
March 1, 2023
7 months
March 17, 2023
May 16, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To establish the immunogenicity of subunit KLH at different doses, with and without aluminium hydroxide or Montanide ISA-51 adjuvants
Proportion of participants with \>2-fold increase over baseline (D0) in anti-KLH IgG antibody titre by ELISA in each group
Day 28
Secondary Outcomes (5)
Determine whether different doses of subunit KLH, with and without aluminium hydroxide or Montanide ISA-51 adjuvants, elicit predominantly TH1, TH2 or balanced responses
Day 28
Within-participant dose-response to intradermal KLH on day Day 28: skin induration response (EC50)
Day 30 (48 hours after Day 28 KLH re-challenge)
Within-participant dose-response to intradermal KLH on day Day 28: skin induration response (Emax)
Day 30 (48 hours after Day 28 KLH re-challenge)
Within-participant dose-response to intradermal KLH on day Day 28: skin erythema response (EC50)
Day 30 (48 hours after Day 28 KLH re-challenge)
Within-participant dose-response to intradermal KLH on day Day 28: skin erythema response (Emax)
Day 30 (48 hours after Day 28 KLH re-challenge)
Study Arms (8)
Group 1: Saline 0.9% (placebo) primary dose
PLACEBO COMPARATORIM saline 0.9% (placebo) day 0, followed by multi-dose ID subunit KLH (0 mcg (saline), 1 mcg, 3 mcg, 10mcg, 30mcg, 100mcg) day 28
Group 2: subunit KLH 1000mcg primary dose
ACTIVE COMPARATORIM dose subunit KLH 1000 mcg day 0, followed by multi-dose ID subunit KLH (0 mcg (saline), 1 mcg, 3 mcg, 10mcg, 30mcg, 100mcg) day 28
Group 3: subunit KLH 1000mcg plus aluminium hydroxide adjuvant 900mcg primary dose
ACTIVE COMPARATORIM dose subunit KLH 1000 mcg plus aluminium hydroxide 900mcg day 0, followed by multi-dose ID subunit KLH (0 mcg (saline), 1 mcg, 3 mcg, 10mcg, 30mcg, 100mcg) day 28
Group 4: subunit KLH 1000mcg plus Montanide ISA-51 primary dose
ACTIVE COMPARATORIM dose subunit KLH 1000 mcg plus Montanide ISA-51 day 0, followed by multi-dose ID subunit KLH (0 mcg (saline), 1 mcg, 3 mcg, 10mcg, 30mcg, 100mcg) day 28
Group 5: subunit KLH 10mcg primary dose
ACTIVE COMPARATORIM dose subunit KLH 10 mcg day 0, followed by multi-dose ID subunit KLH (0 mcg (saline), 1 mcg, 3 mcg, 10mcg, 30mcg, 100mcg) day 28
Group 6: subunit KLH 10mcg plus aluminium hydroxide adjuvant 900mcg primary dose
ACTIVE COMPARATORIM dose subunit KLH 10 mcg plus aluminium hydroxide 900mcg day 0, followed by multi-dose ID subunit KLH (0 mcg (saline), 1 mcg, 3 mcg, 10mcg, 30mcg, 100mcg) day 28
Group 7: subunit KLH 10mcg plus Montanide ISA-51 primary dose
ACTIVE COMPARATORIM dose subunit KLH 10 mcg plus Montanide ISA-51 day 0, followed by multi-dose ID subunit KLH (0 mcg (saline), 1 mcg, 3 mcg, 10mcg, 30mcg, 100mcg) day 28
Group 8: Blood-sample only group (non-randomised)
NO INTERVENTIONNo challenge agent, blood sampling only.
Interventions
Sub-unit Keyhole Limpet Haemocyanin (KLH, Immucothel, Biosyn, Fellbach, Germany)
Placebo intervention.
Montanide ISA-51 (Seppic, France) is a water-in-oil vaccine adjuvant
Alhydrogel is a vaccine adjuvant
Eligibility Criteria
You may qualify if:
- Participant is willing and able to give informed consent for participation in the study and is able to comply with the study protocol.
- Male or female between 18 and 45 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a physician, based on a detailed medical history and a complete physical examination including vital signs and laboratory measurements.
- Body weight \>= 50 kg and body mass index (BMI) within the range 18 to 30 kilogram/meter squared (inclusive).
- Female participants of child bearing potential: Females of child bearing potential are eligible to enter if they are not pregnant (negative pregnancy test on the day of both screening and vaccination) and willing to use effective methods of contraception to prevent pregnancy from the time of first dose to 60 days afterwards.
- Male participants with female partners of child-bearing potential: must agree to use effective methods of contraception from the time of the first dose of challenge agent to 60 days afterwards.
- At least 2 previous doses of a registered SARS-CoV2 vaccination, at least 60 days previously
- Sufficient English language ability to enable appropriate informed consent procedures to be conducted in English
You may not qualify if:
- Antibiotics or antiviral therapy after a serious illness within 30 days of study entry.
- SARS CoV2 (COVID-19) infection within the previous 30 days, diagnosed using PCR test or lateral flow device
- Any use of immunosuppressant or immunomodulatory agents (systemic or topical) in 3 months prior to study entry.
- Chronic medical conditions with potential effect on immune responses including diabetes, significant history of atopy, or any condition that, in the opinion of the investigator, would interfere with the study
- 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.
- Fitzpatrick skin type V and VI (due to potential interference with assessment of DTH response)
- Pregnancy or breastfeeding
- Allergy to KLH, aluminium hydroxide, Montanide ISA-51, related vaccine adjuvants, or components of the study challenge agents
- Allergy to shellfish
- Residency in or significant previous travel to areas endemic for schistosomiasis (due to potential cross-reactive immune responses to KLH)
- Previous exposure to Keyhole Limpet Haemocyanin, e.g. in the context of a previous study
- Participants 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.
- Phobia of needles or minor surgical procedures.
- Current smoker or using nicotine replacement therapy
- Participants receiving any vaccinations within 2 months prior to screening visit, or will require vaccination prior to the end of study follow-up.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
NIHR Oxford Experimental Medicine Clinical Research Facility
Oxford, OX37LE, United Kingdom
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
James Fullerton, MBBS
NDORMS, University of Oxford
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 17, 2023
First Posted
May 25, 2023
Study Start
March 1, 2023
Primary Completion
October 1, 2023
Study Completion
February 1, 2024
Last Updated
May 25, 2023
Record last verified: 2023-03
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- The study team will have exclusive use of the data for a reasonable period of time following the completion of the study in order to complete analysis and secure publication of results.
- Access Criteria
- As per MRC Policy and Guidance on Sharing of Research Data from Population and Patient Studies and the Oxford University Data Sharing Policy, any external users will be required to agree to terms set out in an Oxford University Data Sharing Agreement. The agreement will outline their responsibilities and will prohibit any attempt to identify study participants, breach confidentiality or make unapproved contact with study participants.
Only non-identifiable data anonymised to the ICO Anonymisation: managing data protection risk code of practice generated in this study will be suitable for sharing. We will adhere to the MRC's policy on data sharing. ORA-data offers a means for Oxford's researchers to openly share non-confidential research data, without the need for external data users to undergo authentication. Each deposit is accompanied by appropriate metadata and is assigned a unique Digital Object Identifier (DOI) via the DataCite scheme, allowing it to be cited in publications. Directions to key datasets will also be made available via the group's web page on the Institute's web site. Appropriate metadata will be published with research data to enable other researchers to identify whether the data could be suitable for their own research.