Phase I Trial to Evaluate VLP Peanut in Healthy and Peanut Allergic Subjects

Study Overview
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Brief Summary
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This phase I clinical trial is designed to evaluate the safety and tolerability of VLP Peanut in healthy subjects and in subjects with peanut allergy (PA). This clinical trial will evaluate the immunotoxicity profile of VLP Peanut in healthy subjects and assess the immunotoxicity profile and the degree of reactogenicity (allergenicity) in subjects with PA. This clinical trial will also explore preliminary proof of efficacy of VLP Peanut in subjects with PA.

Official Title
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A Phase I Clinical Trial to Evaluate the Safety and Tolerability of VLP Peanut in Healthy Subjects and Subjects With Peanut Allergy and to Explore Preliminary Signals of Its Efficacy (PROTECT)

Conditions
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Peanut Allergy

Intervention / Treatment
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* Biological: VLP Peanut
* Biological: Placebo
* Biological: VLP Peanut


Participation Criteria
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Eligibility Criteria
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Part A Main Inclusion Criteria: Capable of giving signed informed consent. Subject who has a signed and dated Informed Consent Form (ICF). Subject must be 18 to 50 years inclusive, at the time of signing the ICF. Male or female. Female subjects who are not of childbearing potential (or females of childbearing potential who agree to comply with the contraceptive requirements of the clinical trial protocol). Good general health, as determined by the Investigator. A positive SPT to histamine. The following additional inclusion criteria are only applicable to the healthy subjects in Group A1: Healthy subjects (non-atopic) with no clinically significant co-morbidity (including broncho-reactive airway disease like asthma, current allergic rhinitis, etc.). Subjects with no history of allergy or intolerance to peanut or any other food and who consume peanuts with no effect. Subjects with lack of sensitivity to peanut allergen confirmed by SPT using whole peanut extract. Peanut specific immunoglobulin E (IgE) <0.1 kU/L. Ara h 2 specific IgE <0.1 kU/L. Subjects with negative basophil activation test (BAT). The following additional inclusion criteria are only applicable to the subjects with PA in Group A2: Clinical history of physician diagnosed PA. Peanut allergen sensitivity confirmed by SPT and IgE. Subjects who currently adhere to a strict peanut-free diet and who agree to continue this for the duration of the clinical trial. Subjects who are able to handle and correctly use an adrenaline auto-injector. Part B Main Inclusion Criteria: Capable of giving signed informed consent. Subject who has a signed and dated ICF. Subjects aged 18 to 50 years of age inclusive, at the time of signing the ICF. Male or female. Female subjects who are not of childbearing potential (or females of childbearing potential who agree to comply with the contraceptive requirements of the clinical trial protocol). Clinical history of physician diagnosed PA. Peanut allergen sensitivity confirmed by SPT and IgE. Subjects with positive BAT. Subjects who currently adhere to a strict peanut-free diet and who agree to continue this for the duration of the clinical trial. Good general health, as determined by the Investigator. Subjects who are able to handle and correctly use an adrenaline auto-injector. Main Exclusion Criteria Part A and B: Pregnant or lactating subject. Presence of any medical condition that may reduce the ability to survive a serious allergic reaction. Subjects with atopic dermatitis with >25% skin surface involvement. For subjects with PA, presence of severe, poorly controlled or uncontrolled asthma. History of severe or life-threatening anaphylactic reactions to peanut resulting in neurological compromise or requiring mechanical ventilation. Clinical history of severe systemic or life-threatening anaphylactic reactions to other foods (apart from peanut), insect venom, exercise, drugs, etc. or idiopathic anaphylaxis. Unable to receive epinephrine therapy. Clinical history of drug or alcohol abuse, which, in the Investigator's opinion, could interfere with the subject's ability to participate in the clinical trial. Participation in a clinical research trial with any investigational drug/placebo within 3 months of screening (Visit 1) or concomitantly with this clinical trial. Personal, financial or other dependent relationship (e.g., employee or immediate relative) with the clinical trial site, Sponsor, Sponsor's representative, or another individual who has access to the clinical trial protocol. Vulnerable subjects or those in judicial or governmental detention, detainment or imprisonment in a public institution.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Two part clinical trial: Part A- Open-label with two groups (A1 and A2): i) A1 (Healthy Subjects): subcutaneous (SC) dosing with ascending concentrations of VLP Peanut. ii) A2 (peanut allergic subjects): skin prick test (SPT) performed with ascending concentrations of VLP Peanut. Part B - double-blind, placebo-controlled part that will enroll Peanut Allergic Subjects: subcutaneous (SC) dosing with ascending concentrations of VLP Peanut.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - Group A1<br>4 parallel cohorts (1-4) of adult healthy subjects. Each cohort will receive 6 ascending subcutaneous administrations of VLP Peanut. | Biological: VLP Peanut<br>* solution for subcutaneous administration<br>|
| Experimental: Part A - Group A2<br>Adult peanut allergic subjects, will undergo skin prick tests with ascending concentrations of VLP Peanut. | Biological: VLP Peanut<br>* solution for Skin-prick testing<br>|
| Experimental: Part B - Cohorts 1-4<br>4 parallel cohorts (1-4) of peanut allergic subjects. Each cohort will receive 6 ascending subcutaneous administrations of VLP Peanut. | Biological: VLP Peanut<br>* solution for subcutaneous administration<br>Biological: Placebo<br>* solution for subcutaneous administration<br>|
| Experimental: Part B - Cohort 5<br>Cohort 5 subjects in Part B will receive a single dose of VLP Peanut or Placebo on a dosing day. | Biological: VLP Peanut<br>* solution for subcutaneous administration<br>Biological: Placebo<br>* solution for subcutaneous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of Adverse Events (AEs) (including local and systemic AEs). |  | Group A1: 18 weeks; Part B: 64 weeks (Part B). Group A2: 3 days. | 
| Number of subjects discontinuing prematurely from treatment due to AEs |  | Group A1: 11 weeks Part B: 15 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of fatigue (tiredness) | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Frequency of fatigue (tiredness) | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Incidence of headache | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Frequency of headache | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Incidence of muscle pain | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Frequency of muscle pain | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Incidence of cough | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Frequency of cough | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Incidence of sore throat | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Frequency of sore throat | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Incidence of runny nose | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Frequency of runny nose | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Incidence of chills | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Frequency of chills | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Incidence of fever (i.e. body temperature equal or above 38ºC (100.4ºF)) | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Frequency of fever (i.e. body temperature equal or above 38ºC (100.4ºF)) | Part of solicited pre-specified influenza like symptoms in healthy and peanut allergic subjects. | Group A1: 14 weeks Part B: 16 weeks | 
| Wheal sizes after SPT in subjects with PA (Part A only) | wheal diameter (longest diameter) | 15-20 minutes after skin pricking | 
| Respiratory and Cardiovascular System Alterations as assessed by brief physical examination | Assessment of the respiratory and cardiovascular systems through palpation, auscultation and percussion that are performed by physician to identify any potential abnormalities | On each dosing day - Group A1/Group part B: pre-dose and 30+/-10 minutes post dose; Group A2: pre-skin pricking and 1 hour post-skin pricking | 
| Alterations in the lung function | Spirometry test. Alteration is considered when values obtained are: Forced expiratory volume in one second (FEV1) <80% of predicted with a FEV1/Forced vital capacity (FVC) ratio <75%. | Group A1 and Group Part B: On each dosing day pre-dose and 30 to 60 minutes post-dose; Group A2: pre skin pricking and 1 hour post skin pricking | 
| Alterations in urine pH | Urinalysis Dip-stick: pH | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in urinalysis (protein) | Dip-stick: protein | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in urinalysis (glucose) | Dip-stick: glucose | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in urinalysis (ketones) | Dip-stick: ketones | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in urinalysis (urobilinogen) | Dip-stick: urobilinogen | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in urinalysis (bilirubin) | Dip-stick: bilirubin | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in urinalysis (nitrite) | Dip-stick: nitrite | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Urinalysis (blood) | Dip-stick: blood | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Urinalysis (leukocytes) | Dip-stick: leukocytes | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (Glucose) | Detection of the levels of: Glucose | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (Sodium) | Detection of the levels of: sodium | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (Uric Acid) | Detection of the levels of: uric acid | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (Urea) | Detection of the levels of: urea | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (potassium) | Detection of the levels of: potassium. | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (Calcium) | Detection of the levels of: calcium. | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (Creatinine) | Detection of the levels of: creatinine. | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (chloride) | Detection of the levels of: chloride | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (total protein) | Detection of the levels of: total protein | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (phosphorus) | Detection of the levels of: phosphorus | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (cholesterol) | Detection of the levels of: cholesterol | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (albumin) | Detection of the levels of: albumin | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (total bilirubin) | Detection of the levels of: total bilirubin | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (alkaline phosphatase) | Detection of the levels of: alkaline phosphatase | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (lactate dehydrogenase) | Detection of the levels of: lactate dehydrogenase (LDH) | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (aspartate aminotransferase) | Detection of the levels of: aspartate aminotransferase (AST). | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (Alanine aminotransferase) | Detection of the levels of: Alanine aminotransferase (ALT) | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (gamma-glutamyl transferase) | Detection of the levels of: gamma-glutamyl transferase (GGT) | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Serum Chemistry (C-reactive protein) | Detection of the levels of: C-reactive protein (CRP). | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in hemoglobin levels | Hematology, analysis Hemoglobin levels | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in the hematocrit | Hematology, analysis of the hematocrit | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in Red Blood Cells (RBC) levels | Hematology, analysis of total RBC and RBC indices | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Alterations in White Blood Cells (WBC) levels | Hematology: total WBC and differentials | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Platelet counts alterations | Hematology: platelet count | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks | 
| Serum/Urine Pregnancy Test | In all females of childbearing potential. Serum test at V1 and Urine test at subsequent visits. Confirmatory serum pregnancy test to be conducted if urine test is positive. | Group A1: 18 weeks; Group A2: 2-5 days; Part B: 16 weeks |