A study of the safety of a novel treatment (PVX108) for peanut allergy, conducted in peanut-allergic adults
Phase I trial to assess the safety and tolerability of PVX108 in peanut allergic adults
Aravax Pty Ltd
66 participants
May 10, 2017
Interventional
Conditions
Summary
PVX108 is a novel treatment being developed to treat the underlying cause of peanut allergy. It is anticipated that PVX108 administered by intradermal injection every 2 or 4 weeks will produce immune tolerance to peanut proteins in patients with peanut allergy. The product has been designed to have little or no capacity to induce acute allergic reactions, which is a significant risk with most, if not all other forms of allergen immunotherapy. Clinical trial AVX-001 is the first study of PVX108 to be conducted in humans. Its objectives are to determine the maximum dose that can be safely administered as a single injection, and then also to assess the safety of 9 repeat, escalating doses, administered once every 2 weeks. The study will therefore be conducted in 2 stages. In Stage 1, up to 48 peanut-allergic subjects will receive a single dose of PVX108. The first cohort of 6 subjects will receive the lowest dose of PVX108 (or placebo) and be monitored for 24 hours in clinic for adverse events and other clinical effects. A safety review committee will review the results obtained in this cohort. If the committee judges that it is safe to do so, dosing in the next cohort will progress at the next dose level. Dose will be escalated in each cohort until the safety review committee determines that the maximum safe dose of PVX108 has been determined. In Stage 2, up to 18 peanut-allergic subjects will commence the study at the maximum safe starting dose of PVX108. If the dose is well tolerated, an increased dose will be administered 2 weeks later. Subjects will receive a maximum of 6 administrations over a 16 week period. Adverse events and other clinical effects will be monitored periodically during treatment and for 4 weeks after the last dose. A range of blood samples will be collected from subjects prior to, during and after treatment to address an exploratory objective to investigate potential biomarkers of disease and the effects of PVX108 therapy.
Eligibility
Inclusion Criteria10
- Males or females aged 18 to 65 years inclusive at the time of consent
- Documented history of allergic reactivity to peanut regardless of severity
- Positive response to peanut in a basophil activation test
- Peanut-specific serum immunoglobulin E (IgE) measured by ImmunoCAP (Registered Trademark) >0.35 kUA/L
- Positive skin prick test (SPT) to peanut with a wheal diameter at least 3 mm, unless in the opinion of the investigator, it is unsafe to perform a SPT
- Spirometry testing lung function within the normal range, Forced Expiratory Volume in 1 second (FEV1) at least 80% of predicted at Screening and Visit 1
- Bronchodilator reversibility test with change in FEV1 less than 12% and less than 200 mL
- Female subjects must be:
- a. of non child-bearing potential [surgically sterilised or post–menopausal (12 months with no menses without alternative medical cause)] OR
- b. not pregnant, breast feeding or planning to become pregnant AND willing to comply with the medically acceptable contraceptive requirements of the study from Screening to at least 28 days after the last Investigational Medicinal Product (IMP) administration
Exclusion Criteria9
- History of or current clinically-significant gastrointestinal, hepatic, renal, cardiovascular, endocrine, oncological, immunological, neurological, ophthalmological, haematological, respiratory or psychiatric disorder or any other condition, which in the opinion of the investigator or sponsor would jeopardise the safety of the subject or the validity of the study results
- Random serum tryptase reading less than 11.4 ng/mL
- Severe or unstable asthma
- History of respiratory related life threatening events or life threatening anaphylaxis in the last 12 months
- Subjects with skin disorders that would hinder skin testing and/or its interpretation (eg severe generalised active atopic dermatitis)
- Subjects unable to receive beta-2-agonist or anticholinergics that could hinder treatment of an asthmatic response
- Use of beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers, systemic (oral or injectable) corticosteroids within 2 months prior to Day 1
- Prior participation in any interventional study aimed at desensitising peanut allergy within the last 5 years
- Subject who received any specific immunotherapy for allergy during the past 12 months, or plans to receive during the course of the study
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Interventions
PVX108 comprises an equimolar solution of unmodified synthetic peptides representing T cell epitope sequences from major peanut allergens (Ara h 1 and Ara h 2). It is administered by intradermal injection. In Stage 1 of the trial, up to eight cohorts of six subjects will receive single injections of PVX108 or matched placebo (2:1). The first cohort will receive a dose of 0.05nmol. If the dose is well tolerated, the dose will be escalated in the next cohort up to a maximum of 150nmol in cohort 8. In Stage 2 of the trial, 18 subjects will receive six injections of PVX108 or matched placebo (2:1) at week 0, 2, 4, 8, 12, and 16. Dosing will commence at the safe starting dose identified in Stage 1, and if well tolerated will be escalated up to a maximum of 150nmol. The maximum total duration of treatment will be 16 weeks.
Locations(2)
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ACTRN12617000692336