Immune System Diseases, Peanut Allergy, Peanut Hypersensitivity, Peanut-Induced Anaphylaxis
Conditions
Keywords
Peanut allergy, Arachis, Child, Adolescent, Immunotherapy
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.
Interventions
BIOLOGICALPVX-108
PVX108 comprises a mixture of peptides that represent sequences from peanut allergens
BIOLOGICALPlacebo
Matching placebo comprises the formulation vehicle without peptides
Sponsors
Aravax Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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 | — |
| 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. |
Other
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Australia, United States
Outcome results
None listed