A Safety and Efficacy Study of PVX108 in Children and Adolescents With Peanut Allergy

Study Overview
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Brief Summary
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The overall aims of this study are to demonstrate that treatment with PVX108 immunotherapy has an acceptable safety profile and is effective for reducing clinical reactivity to peanut protein in children and adolescents with peanut allergy.

Official Title
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A Safety and Efficacy Study of PVX108 in Children and Adolescents With Peanut Allergy

Conditions
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Peanut Allergy, Peanut Hypersensitivity, Peanut-Induced Anaphylaxis, Immune System Diseases

Intervention / Treatment
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* Biological: PVX-108
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Physician-diagnosed immunoglobulin E (IgE) mediated peanut allergy; Peanut specific serum IgE measured by ImmunoCAP® ≥ 0.7 kilounit allergy specific antibody per litre (kUA/L) at screening; Positive skin prick test to peanut with mean wheal diameter ≥5 mm greater than negative control at screening; Positive peanut double blind placebo-controlled food challenge (DBPCFC) with a reactive dose ≤300 mg peanut protein (≤443 mg cumulative reactive dose [CRD]); Able to perform spirometry or peak expiratory flow. Children who are 4 years of age at Screening Stage 1 visit and unable to perform peak expiratory may be enrolled providing they had no clinical features of moderate or severe persistent asthma within 1 year prior to the Screening visit; Forced expiratory volume in 1 second (FEV1) ≥80% predicted in adolescents and children with asthma capable of performing spirometry, or peak expiratory flow ≥80% predicted in participants with asthma unable to perform spirometry (at investigator's discretion). Key Exclusion Criteria: History of or current clinically significant medical conditions or laboratory abnormalities which in the opinion of the investigator would jeopardise the safety of the participant or the validity of the study results; Severe or unstable asthma as assessed by the Global Initiative for Asthma (GINA) assessment of asthma control OR current treatment for asthma at GINA ≥Step 4 level; Participants with skin disorders that would hinder skin prick testing and/or its interpretation or study drug administration (eg, severe generalised poorly controllable atopic dermatitis); Any medical condition in which epinephrine (adrenaline) is contraindicated; Prior therapy aimed at desensitising peanut allergy, either in a formal study or in clinical practice; Severe or life-threatening reaction during the screening food challenge, at investigator discretion.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PVX108 50 nmol in adolescents<br>Twelve 4-weekly intradermal (ID) doses of PVX108 at 50 nmol in adolescents (Cohort 1) | Biological: PVX-108<br>* PVX108 comprises a mixture of peptides that represent sequences from peanut allergens<br>|
| Placebo Comparator: Placebo in adolescents<br>Twelve 4-weekly ID doses of placebo matching PVX108 in adolescents (Cohort 1) | Biological: Placebo<br>* Matching placebo comprises the formulation vehicle without peptides<br>|
| Experimental: PVX108 5 nmol in children<br>Twelve 4-weekly ID doses of PVX108 at 5 nmol in children (Cohort 2) | Biological: PVX-108<br>* PVX108 comprises a mixture of peptides that represent sequences from peanut allergens<br>|
| Experimental: PVX108 50 nmol in children<br>Twelve 4-weekly ID doses of PVX108 at 50 nmol in children (Cohort 2) | Biological: PVX-108<br>* PVX108 comprises a mixture of peptides that represent sequences from peanut allergens<br>|
| Placebo Comparator: Placebo in children<br>Twelve 4-weekly ID doses of placebo matching PVX-108 in children (Cohort 2) | Biological: Placebo<br>* Matching placebo comprises the formulation vehicle without peptides<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of maximum tolerated dose (MTD) of peanut protein at the Week 46 double blind placebo-controlled food challenge (DBPCFC) relative to baseline in children aged 4 to 11 years treated with PVX108 compared to placebo |  | 46 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of MTD of peanut protein at the Week 71 DBPCFC relative to baseline in children aged 4 to 11 years treated with PVX108 compared to placebo |  | 71 weeks | 
| Percentage of children aged 4 to 11 years treated with PVX108 who achieve an MTD of at least 300 mg, 600 mg and 1000 mg at the Week 46 DBPCFC compared to placebo |  | 46 weeks | 
| Percentage of children aged 4 to 11 years treated with PVX108 who achieve an MTD of at least 300 mg, 600 mg and 1000 mg at the Week 71 DBPCFC compared to placebo |  | 71 weeks | 
| Ratio of cumulative reactive dose (CRD) of peanut protein at the Week 46 DBPCFC relative to baseline in children aged 4 to 11 years treated with PVX108 compared to placebo |  | 46 weeks | 
| Ratio of CRD of peanut protein at the Week 71 DBPCFC relative to baseline in children aged 4 to 11 years treated with PVX108 compared to placebo |  | 71 weeks | 
| Percentage of treatment responders at the Week 46 DBPCFC in children aged 4 to 11 years treated with PVX108 compared to placebo |  | 46 weeks | 
| Percentage of treatment responders at the Week 71 DBPCFC in children aged 4 to 11 years treated with PVX108 compared to placebo |  | 71 weeks | 
| Frequency of events of each severity grade during the Week 46 DBPCFC in children aged 4 to 11 years treated with PVX108 compared to placebo |  | 46 weeks | 
| Frequency of events of each severity grade during the Week 71 DBPCFC in children aged 4 to 11 years treated with PVX108 compared to placebo |  | 71 weeks | 
| Treatment emergent adverse events (TEAEs) and Serious adverse events (SAEs) during 45 weeks treatment and 26 weeks following treatment with PVX108 compared to placebo | Incidence and severity of TEAEs (graded according to FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers, 2007) including SAEs, TEAEs leading to study discontinuation, anaphylaxis with temporal association to investigational product (IP) administration, use of epinephrine (adrenaline) as rescue medication after IP administration, and injection site reactions. | Up to 74 weeks | 
| Change from baseline in peak expiratory flow |  | Up to 73 weeks | 
| Severity of symptoms upon unintentional exposure to peanut (graded according to FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers, 2007) |  | Up to 73 weeks | 
| Incidence of anti-drug antibodies (ADAs) associated with clinically significant TEAEs |  | Up to 46 weeks | 
| Number of participants with abnormal physical examination data |  | Up to 74 weeks | 
| Incidence of concomitant medication use |  | Up to 74 weeks | 
| Number of participants with abnormal clinical laboratory data |  | Up to 74 weeks | 
| Number of participants with abnormal vital signs |  | Up to 74 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peanut allergy, Arachis, Child, Adolescent, Immunotherapy