KLH Challenge to Explore the Human Immune Response

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.

Conditions

• Immune Response

Interventions

BIOLOGICAL

Keyhole-Limpet Hemocyanin

Sub-unit Keyhole Limpet Haemocyanin (KLH, Immucothel, Biosyn, Fellbach, Germany)

DRUG

Saline

Placebo intervention.

DRUG

Montanide ISA 51 VG

Montanide ISA-51 (Seppic, France) is a water-in-oil vaccine adjuvant

DRUG

Alhydrogel

Alhydrogel is a vaccine adjuvant

Sponsors & Collaborators

• University of Oxford

  lead OTHER

Principal Investigators

• James Fullerton, MBBS · NDORMS, University of Oxford

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-03-01

Primary Completion

2023-10-31

Completion

2024-02-29

Countries

• United Kingdom

Study Locations