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

Sponsor

Aravax Pty Ltd (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05621317

Collaborator

(none)

Enrollment

Locations

Arms

28.9

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Peanut Allergy Peanut Hypersensitivity Peanut-Induced Anaphylaxis Immune System Diseases	Biological: PVX-108 Biological: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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 [Up to 74 weeks]
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.
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]

Other Outcome Measures

Ratio of MTD of peanut protein at the Week 46 DBPCFC relative to baseline in adolescents aged 12 to 17 years treated with PVX108 compared to placebo [46 weeks]
Ratio of MTD of peanut protein at the Week 71 DBPCFC relative to baseline in adolescents aged 12 to 17 years treated with PVX108 compared to placebo [71 weeks]
Percentage of adolescents aged 12 to 17 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 adolescents aged 12 to 17 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 CRD of peanut protein at Week 46 DBPCFC relative to baseline in adolescents aged 12 to 17 years treated with PVX108 compared to placebo [46 weeks]
Ratio of CRD of peanut protein at Week 71 DBPCFC relative to baseline in adolescents aged 12 to 17 years treated with PVX108 compared to placebo [71 weeks]
Percentage of treatment responders at the Week 46 DBPCFC in adolescents aged 12 to 17 years treated with PVX108 compared to placebo [46 weeks]
Percentage of treatment responders at the Week 71 DBPCFC in adolescents aged 12 to 17 years treated with PVX108 compared to placebo [71 weeks]
Frequency of events of each severity grade during the Week 46 DBPCFC in adolescents aged 12 to 17 years treated with PVX108 compared to placebo [46 weeks]
Frequency of events of each severity grade during the Week 71 DBPCFC in adolescents aged 12 to 17 years treated with PVX108 compared to placebo [71 weeks]
Changes from baseline in allergen specific immunoglobulins after 45 weeks treatment with PVX108 compared to placebo [Up to 74 weeks]
Changes from baseline in cellular immune response after 45 weeks treatment with PVX108 compared to placebo: Exploratory [Up to 74 weeks]
Changes from baseline in titrated peanut skin prick test (SPT) response after 45 weeks treatment with PVX108 compared to placebo [Up to 74 weeks]
Proportion of participants in each cohort who develop treatment-induced or treatment-enhanced ADAs during 45 weeks treatment with PVX108 compared to placebo [45 weeks]
Change from baseline in Food Allergy Related Quality of Life Questionnaire Child Form (FAQLQ-CF) score (Range 1-7, higher score indicates worse outcome) at Week 46 and at Week 71 in children enrolled in Cohort 2 treated with PVX108 compared to placebo [Up to 71 weeks]
Change from baseline in FAQLQ-Teenager Form (FAQLQ-TF) score (Range 1-7, higher score indicates worse outcome) at Week 46 and at Week 71 in adolescents enrolled in Cohort 1 treated with PVX108 compared to placebo [Up to 71 weeks]
Change from baseline in Food Allergy Independent Measure (FAIM) score (Range 1-7, higher score indicates worse outcome) at Week 46 and at Week 71 in children enrolled in Cohort 2 treated with PVX108 compared to placebo [Up to 71 weeks]
Change from baseline in FAIM score (Range 1-7, higher score indicates worse outcome) at Week 46 and at Week 71 in adolescents enrolled in Cohort 1 treated with PVX108 compared to placebo [Up to 71 weeks]
Change from baseline in FAQLQ-Parent Form (FAQLP-PF) score (Range 1-7, higher score indicates worse outcome) at Week 46 and at Week 71 in children enrolled in Cohort 2 treated with PVX108 compared to placebo [Up to 71 weeks]
Change from baseline in FAQLQ-Parent Form Teenager (FAQLQ-PFT) score (Range 1-7, higher score indicates worse outcome) at Week 46 and at Week 71 in adolescents enrolled in Cohort 1 treated with PVX108 compared to placebo [Up to 71 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country
1	Sydney Children's Hospital	Randwick	New South Wales	Australia
2	The Children's Hospital at Westmead	Westmead	New South Wales	Australia
3	Women's and Children's Hospital	North Adelaide	South Australia	Australia
4	The Royal Children's Hospital Melbourne	Parkville	Victoria	Australia
5	Perth Children's Hospital	Nedlands	Western Australia	Australia