Peanut Oral Immunotherapy Study of Early Intervention for Desensitization
Condition: Peanut Allergy
MeSH terms: Hypersensitivity; Peanut Hypersensitivity
Intervention: AR101 powder provided in capsules & sachets; Placebo powder provided in capsules & sachets
Intervention description: Study product formulated to contain peanut protein at different dosage strengths for use as defined in the protocol; Study product formulated to contain only inactive ingredients for use as defined in the protocol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 2:1 randomization
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Double-Blinded
Enrollment: 146.0
Sex: All
Minimum age: 1 Year
Maximum age: 3 Years
Healthy volunteers: No
Keywords: CODIT™ (characterized oral desensitization immunotherapy™); Peanut-Allergic Children; CPNA (Characterized Peanut Allergen); Desensitization; AR101; Allergy; Peanut Allergy; Characterized Peanut Allergen; Oral Immunotherapy

Summary:

      The purpose of this study is to determine the efficacy and safety of AR101 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.