Clinical trial NCT05621317: A Safety and Efficacy Study of PVX108 in Children and Adolescents with Peanut Allergy
Official title: A Safety and Efficacy Study of PVX108 in Children and Adolescents with Peanut Allergy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Peanut Allergy
Peanut Hypersensitivity
Peanut-Induced Anaphylaxis
Immune System Diseases
Keywords: Peanut allergy
Arachis
Child
Adolescent
Immunotherapy
Lead sponsor: Aravax Pty Ltd
Sponsor class: INDUSTRY
First posted: 2022-11-18
Enrollment: 90
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: 46 weeks
Secondary outcomes:
measure: 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
timeFrame: 71 weeks
measure: 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
timeFrame: 46 weeks
measure: 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
timeFrame: 71 weeks
measure: 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
timeFrame: 46 weeks
measure: 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
timeFrame: 71 weeks
measure: Percentage of treatment responders at the Week 46 DBPCFC in children aged 4 to 11 years treated with PVX108 compared to placebo
timeFrame: 46 weeks
measure: Percentage of treatment responders at the Week 71 DBPCFC in children aged 4 to 11 years treated with PVX108 compared to placebo
timeFrame: 71 weeks
measure: 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
timeFrame: 46 weeks
measure: 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
timeFrame: 71 weeks
measure: Treatment emergent adverse events (TEAEs) and Serious adverse events (SAEs) during 45 weeks treatment and 26 weeks following treatment with PVX108 compared to placebo
timeFrame: Up to 74 weeks
measure: Change from baseline in peak expiratory flow
timeFrame: Up to 73 weeks
measure: Severity of symptoms upon unintentional exposure to peanut (graded according to FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers, 2007)
timeFrame: Up to 73 weeks
measure: Incidence of anti-drug antibodies (ADAs) associated with clinically significant TEAEs
timeFrame: Up to 46 weeks
measure: Number of participants with abnormal physical examination data
timeFrame: Up to 74 weeks
measure: Incidence of concomitant medication use
timeFrame: Up to 74 weeks
measure: Number of participants with abnormal clinical laboratory data
timeFrame: Up to 74 weeks
measure: Number of participants with abnormal vital signs
timeFrame: Up to 74 weeks
Other outcomes:
measure: 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
timeFrame: 46 weeks
measure: 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
timeFrame: 71 weeks
measure: 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
timeFrame: 46 weeks
measure: 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
timeFrame: 71 weeks
measure: 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
timeFrame: 46 weeks
measure: 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
timeFrame: 71 weeks
measure: Percentage of treatment responders at the Week 46 DBPCFC in adolescents aged 12 to 17 years treated with PVX108 compared to placebo
timeFrame: 46 weeks
measure: Percentage of treatment responders at the Week 71 DBPCFC in adolescents aged 12 to 17 years treated with PVX108 compared to placebo
timeFrame: 71 weeks
measure: 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
timeFrame: 46 weeks
measure: 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
timeFrame: 71 weeks
measure: Changes from baseline in allergen specific immunoglobulins after 45 weeks treatment with PVX108 compared to placebo
timeFrame: Up to 74 weeks
measure: Changes from baseline in cellular immune response after 45 weeks treatment with PVX108 compared to placebo: Exploratory
timeFrame: Up to 74 weeks
measure: Changes from baseline in titrated peanut skin prick test (SPT) response after 45 weeks treatment with PVX108 compared to placebo
timeFrame: Up to 74 weeks
measure: Proportion of participants in each cohort who develop treatment-induced or treatment-enhanced ADAs during 45 weeks treatment with PVX108 compared to placebo
timeFrame: 45 weeks
measure: 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
timeFrame: Up to 71 weeks
measure: 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
timeFrame: Up to 71 weeks
measure: 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
timeFrame: Up to 71 weeks
measure: 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
timeFrame: Up to 71 weeks
measure: 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
timeFrame: Up to 71 weeks
measure: 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
timeFrame: Up to 71 weeks
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Research Institute
state: Arkansas
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates
state: California
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Indianapolis
country: United States
facility: Riley Children's Hospital at IU
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Chevy Chase
country: United States
facility: IAA Clinical Research
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Randwick
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: North Adelaide
country: Australia
facility: Women's and Children's Hospital
state: South Australia
city: Parkville
country: Australia
facility: The Royal Children's Hospital Melbourne
state: Victoria
city: Nedlands
country: Australia
facility: Perth Children's Hospital
state: Western Australia
Study officials:
affiliation: Emory University
name: Brian Vickery, MD
role: PRINCIPAL_INVESTIGATOR
References: