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

• ClinicalTrials.gov Identifier: NCT05621317
• Recruitment Status: Recruiting
• First Posted: November 18, 2022
• Last Update Posted: March 17, 2023
• Sponsor: Aravax Pty Ltd
• Information provided by (Responsible Party): Aravax Pty Ltd

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 (Clinical Trial)
• Estimated 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
• Actual Study Start Date: February 9, 2023
• Estimated Primary Completion Date: November 2024
• Estimated Study Completion Date: July 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 :

1. 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 [ Time Frame: 46 weeks ]

Secondary Outcome Measures :

1. 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 [ Time Frame: 71 weeks ]
2. 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 [ Time Frame: 46 weeks ]
3. 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 [ Time Frame: 71 weeks ]
4. 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 [ Time Frame: 46 weeks ]
5. 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 [ Time Frame: 71 weeks ]
6. Percentage of treatment responders at the Week 46 DBPCFC in children aged 4 to 11 years treated with PVX108 compared to placebo [ Time Frame: 46 weeks ]
7. Percentage of treatment responders at the Week 71 DBPCFC in children aged 4 to 11 years treated with PVX108 compared to placebo [ Time Frame: 71 weeks ]
8. 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 [ Time Frame: 46 weeks ]
9. 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 [ Time Frame: 71 weeks ]
10. Treatment emergent adverse events (TEAEs) and Serious adverse events (SAEs) during 45 weeks treatment and 26 weeks following treatment with PVX108 compared to placebo [ Time Frame: 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.
11. Change from baseline in peak expiratory flow [ Time Frame: Up to 73 weeks ]
12. Severity of symptoms upon unintentional exposure to peanut (graded according to FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers, 2007) [ Time Frame: Up to 73 weeks ]
13. Incidence of anti-drug antibodies (ADAs) associated with clinically significant TEAEs [ Time Frame: Up to 46 weeks ]
14. Number of participants with abnormal physical examination data [ Time Frame: Up to 74 weeks ]
15. Incidence of concomitant medication use [ Time Frame: Up to 74 weeks ]
16. Number of participants with abnormal clinical laboratory data [ Time Frame: Up to 74 weeks ]
17. Number of participants with abnormal vital signs [ Time Frame: Up to 74 weeks ]

Other Outcome Measures:

1. 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 [ Time Frame: 46 weeks ]
2. 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 [ Time Frame: 71 weeks ]
3. 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 [ Time Frame: 46 weeks ]
4. 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 [ Time Frame: 71 weeks ]
5. 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 [ Time Frame: 46 weeks ]
6. 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 [ Time Frame: 71 weeks ]
7. Percentage of treatment responders at the Week 46 DBPCFC in adolescents aged 12 to 17 years treated with PVX108 compared to placebo [ Time Frame: 46 weeks ]
8. Percentage of treatment responders at the Week 71 DBPCFC in adolescents aged 12 to 17 years treated with PVX108 compared to placebo [ Time Frame: 71 weeks ]
9. 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 [ Time Frame: 46 weeks ]
10. 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 [ Time Frame: 71 weeks ]
11. Changes from baseline in allergen specific immunoglobulins after 45 weeks treatment with PVX108 compared to placebo [ Time Frame: Up to 74 weeks ]
12. Changes from baseline in cellular immune response after 45 weeks treatment with PVX108 compared to placebo: Exploratory [ Time Frame: Up to 74 weeks ]
13. Changes from baseline in titrated peanut skin prick test (SPT) response after 45 weeks treatment with PVX108 compared to placebo [ Time Frame: Up to 74 weeks ]
14. Proportion of participants in each cohort who develop treatment-induced or treatment-enhanced ADAs during 45 weeks treatment with PVX108 compared to placebo [ Time Frame: 45 weeks ]
15. 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 [ Time Frame: Up to 71 weeks ]
16. 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 [ Time Frame: Up to 71 weeks ]
17. 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 [ Time Frame: Up to 71 weeks ]
18. 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 [ Time Frame: Up to 71 weeks ]
19. 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 [ Time Frame: Up to 71 weeks ]
20. 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 [ Time Frame: Up to 71 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Australia, New South Wales

Sydney Children's Hospital; Not yet recruiting

Randwick, New South Wales, Australia

Contact: Wainstein +61 (02) 9382 5534 SCHN-SCHClinicalTrials@health.nsw.gov.au

The Children's Hospital at Westmead; Not yet recruiting

Westmead, New South Wales, Australia

Contact: Ford +61 (02) 9845 3418 SCHN-CHW-AllergyResearch@health.nsw.gov.au

Australia, South Australia

Women's and Children's Hospital; Not yet recruiting

North Adelaide, South Australia, Australia

Contact: Quinn +61 (08) 8161 9156 health.wchnallergyresearch@sa.gov.au

Australia, Victoria

The Royal Children's Hospital Melbourne; Recruiting

Parkville, Victoria, Australia

Contact: Perrett +61 (0)426 427 944 aravax.peanut@mcri.edu.au

Australia, Western Australia

Perth Children's Hospital; Not yet recruiting

Nedlands, Western Australia, Australia

Contact: O'Sullivan +61(08) 6456 4360 foodallergyresearch@health.wa.gov.au

Sponsors and Collaborators

Aravax Pty Ltd

Investigators

• Principal Investigator: Brian Vickery, MD; Emory University

More Information

• Responsible Party: Aravax Pty Ltd
• ClinicalTrials.gov Identifier: NCT05621317
• Other Study ID Numbers: AVX-201
• First Posted: November 18, 2022
• Last Update Posted: March 17, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aravax Pty Ltd:

Peanut allergy; Arachis; Child; Adolescent; Immunotherapy

Additional relevant MeSH terms:

Hypersensitivity; Peanut Hypersensitivity; Immune System Diseases; Anaphylaxis; Nut and Peanut Hypersensitivity; Food Hypersensitivity; Hypersensitivity, Immediate