Clinical trial NCT03736447: Peanut Oral Immunotherapy Study of Early Intervention for Desensitization
Official title: Peanut Oral Immunotherapy Study of Early Intervention for Desensitization (POSEIDON)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Peanut Allergy
Keywords: CODIT™ (characterized oral desensitization immunotherapy™)
Peanut-Allergic Children
CPNA (Characterized Peanut Allergen)
Desensitization
AR101
Allergy
Peanut Allergy
Characterized Peanut Allergen
Oral Immunotherapy
Lead sponsor: Aimmune Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-11-09
Enrollment: 146
Sex: ALL
Minimum age (years): 1
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2:1 randomization
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the efficacy and safety of AR101 in peanut-allergic children aged 1 to \< 4 years.

Detailed description: This is a Phase 3, randomized, double-blind, placebo-controlled study conducted at 14 study sites in North America and 9 in Europe to evaluate the efficacy and safety of AR101 in a characterized oral desensitization immunotherapy (CODIT™) regimen compared with placebo in peanut-allergic children aged 1 to \< 4 years.

Eligibility criteria: Inclusion Criteria:

* Aged 1 to \< 4 years at randomization.
* Written informed consent from the legal guardian/parent (or both parents where required by local authorities). Provide assent where required and as appropriate per local requirements.
* Sensitivity to peanut, defined as one of the following:

  * No known history of peanut ingestion and has serum IgE to peanut ≥ 5 kUA/L within 12 months before randomization.
  * Documented history of physician-diagnosed IgE-mediated peanut allergy that includes the onset of characteristic\* signs and symptoms of allergy within 2 hours of known oral exposure to peanut or peanut-containing food, and has a mean wheal diameter on skin prick test (SPT) to peanut of at least 3 mm greater than the negative control (diluent) or serum IgE to peanut ≥ 0.35 kUA/L, obtained within 12 months before randomization.
* Development of age-appropriate dose-limiting allergy symptoms after consuming single doses of peanut protein \> 3 mg to ≤ 300 mg in a screening DBPCFC.
* A palatable vehicle food to which the subject is not allergic must be available for administering study product.

Exclusion Criteria:

* History of severe or life-threatening anaphylaxis anytime before the screening DBPCFC.
* History of hemodynamically significant cardiovascular or renovascular disease, including uncontrolled or inadequately controlled hypertension.
* History of biopsy-confirmed diagnosis of EoE; other eosinophilic GI disease; chronic, recurrent, or severe gastroesophageal reflux disease (GERD); or symptoms of dysphagia (eg, difficulty swallowing, food "getting stuck").
* Recurrent GI symptoms considered clinically significant in the opinion of the investigator.
* History of a mast cell disorder including mastocytosis, urticaria pigmentosa, chronic idiopathic or chronic physical urticaria beyond simple dermatographism (eg, cold urticaria, cholinergic urticaria), and hereditary or idiopathic angioedema.
* Moderate or severe persistent asthma (criteria steps 3-6; National Heart, Lung, and Blood Institute \[NHLBI\], 2007).
* Mild asthma (criteria steps 1-2; NHLBI, 2007) that is uncontrolled or difficult to control based on NHLBI 2007 criteria.
* History of high-dose corticosteroid use (eg, 1-2 mg/kg prednisone or equivalent for \> 3 days) by any route of administration as defined by any of the following:

  * Steroid administered daily for \> 1 month within 1 year before screening
  * One steroid course within 6 months before screening
  * More than 2 steroid courses ≥ 1 week in duration within 1 year before screening
* History of food protein-induced enterocolitis syndrome (FPIES) within 12 months before screening.
* Recurrent urticaria.
* History of failure to thrive or any other form of abnormal growth, or developmental or speech delay that precludes age-appropriate communication.
* History of chronic disease (except mild intermittent asthma, mild persistent asthma that is controlled, atopic dermatitis, or allergic rhinitis) that is or is at significant risk of becoming unstable or requiring a change in a chronic therapeutic regimen.
* Unable to discontinue antihistamines and other medications that could interfere with the assessment of an allergic reaction for 5 half-lives of the medication before the screening SPT, first day of dose escalation, and DBPCFCs.
* Use or anticipated use of a prohibited medication (eg, beta blockers \[oral\], angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, or tricyclic antidepressants), monoclonal antibody, or any other immunomodulatory therapy (including immunosuppressive medications).
* Treatment with any form of immunotherapy for any food allergy anytime before screening.
* Participation in another clinical trial within 30 days or 5 half-lives of the investigational product, whichever is longer, before screening.
* Allergy to oat or rice.
* Hypersensitivity to epinephrine or any of the excipients in the epinephrine auto-injector.
* Parent/caregiver unable or unwilling to use epinephrine auto-injectors.
* Unable to follow the protocol requirements.
* Any other condition (concurrent disease, infection, comorbidity, or psychiatric or psychological disorders) or reason that may interfere with the ability to participate in the study, cause undue risk, or complicate the interpretation of data, in the opinion of the investigator or medical monitor.
* Resides at the same place as another subject in any AR101 interventional trial.
* Lives in the same household and/or is a family member of a sponsor employee or site staff involved in conducting this study.

Primary outcomes:
measure: Percentage of Subjects Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)
timeFrame: 12 months
Secondary outcomes:
measure: Percentage of Subjects Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) [Time Frame: 12 Months]
timeFrame: 12 months
measure: Percentage of Subjects Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)
timeFrame: 12 months
measure: Maximum Severity of Symptoms in Participants at Any Challenge Dose During the Exit Double-blind Placebo Controlled Food Challenge (DBPCFC)
timeFrame: 12 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Mountain View
country: United States
facility: Sean N. Parker Center for Allergy & Asthma Reseach, LPCH at El Camino Hospital
state: California
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates, Inc.
state: California
city: San Diego
country: United States
facility: Allergy & Asthma Medical Group and Research Center
state: California
city: Atlanta
country: United States
facility: Children's Center for Advanced Pediatrics Clinical Research Lab
state: Georgia
city: Marietta
country: United States
facility: Atlanta Allergy & Asthma Clinic
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: The John Hopkins Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Division of Allergy and Clinical Immunology
state: Michigan
city: Ocean City
country: United States
facility: Atlantic Research Center
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Chapel Hill
country: United States
facility: UNC-CH School of Medicine, Pediatric Allergy, Immunology & Rheumatology, Food Allergy
state: North Carolina
city: Charlotte
country: United States
facility: Clinical Research of Charlotte
state: North Carolina
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Lille
country: France
facility: Jeanne de Flandre Hospital
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin
city: Frankfurt am Main
country: Germany
facility: University of Frankfurt
city: Gorleston-on-Sea
country: United Kingdom
facility: James Paget University Hospital
state: Norfolk
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Guy's and St. Thomas' NHS Foundation Trust, Snowy Owl, First Floor, Evelina Children's Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital Central Manchester University Hospitals
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton Foundation NHS Trust Southampton General Hospital
Study officials:
affiliation: Aimmune Therapeutics
name: Director of Regulatory Affairs
role: STUDY_DIRECTOR
References: