Peanut Sublingual Immunotherapy (SLIT)-Tablet for Treatment of Peanut Allergy

This is a phase I/II, dose-escalation, multi-site trial including subjects with peanut allergy confirmed by screening double-blind, placebo-controlled food challenge. The trial is conducted in 3 parts; part 1 will determine the entry dose of the up-dosing regimen (UDR) in adults and adolescents; part 2 will characterize the tolerability of the up-dosing regimen in adults, adolescents and children; part 3 will evaluate the efficacy of 2 maintenance doses of the SLIT-tablet primarily in adolescents and children; a small number of adults may also be included.

Peanut SLIT tablets administered as 9 doses covering a 4000-fold increase in dose will be used in the study.

In part 1, subjects will receive a peanut SLIT-tablet with one of five doses once daily for 2 weeks.

In part 2, subjects will receive a series of increasing doses of the peanut SLIT-tablet, where each dose is taken once daily for 2 weeks. The entry dose for the up-dosing regimen will be determined from part 1.

In part 3, subjects will be randomized into 3 treatment groups (UDR and Maintenance A, UDR and Maintenance B, Placebo UDR and Placebo). Subjects will receive a series of increasing doses of the peanut SLIT-tablet , where each dose is taken once daily for 2 weeks, followed by Maintenance A or B once daily for 24 weeks; or the corresponding Placebo.

The trial will consist of up to 10 cohorts (part 1 is cohort 1-5; part 2 is cohort 6-10) and 3 treatment groups in part 3.

KEY INCLUSION CRITERIA:

Subjects are eligible to be included in the trial only if all the following criteria apply:

• Part 1: Male or female aged 12 through 65 years (inclusive) on the day of enrollment Part 2: Male or female aged 4 through 65 years (inclusive) on the day of enrollment Part 3: Male or female aged 4 through 65 years (inclusive) on the day of randomization
• Documented clinical history of an IgE-mediated allergic reaction towards peanut- containing food
• Peanut-specific serum IgE ≥ 0.7 kU/L at screening measured at central laboratory
• Skin prick test to peanut ≥ 5 mm at screening
• Cohorts 1-8: Experience dose-limiting symptoms at the 10 mg, 30 mg or 100 mg challenge dose of peanut protein on screening DBPCFC Cohorts 9-10: Experience dose-limiting symptoms at the 1 mg or 3 mg challenge dose of peanut protein on the screening DBPCFC Part 3: Experience dose-limiting symptoms at the 3 mg, 10 mg, 30 mg or 100 mg challenge dose of peanut protein on screening DBPCFC

KEY EXCLUSION CRITERIA:

Subjects are excluded from the trial if any of the following criteria apply:

• Diagnosis or history of eosinophilic esophagitis
• Uncontrolled asthma as defined by the Asthma Control Test questionnaire with a score of 19 or below at enrollment (subjects with a diagnosis of asthma only)
• All subjects ≥ 5 years old with FEV1 or PEFR < 70% of predicted value at enrollment Subjects 4 years old with a history of recurrent wheeze requiring inhaled corticosteroids for 2 consecutive weeks or more within 3 months prior to enrollment
• Up-dosing with any allergy immunotherapy product. Maintenance dose of any subcutaneous immunotherapy product other than peanut is allowed
• History of peanut oral immunotherapy within the last 12 months prior to visit 1
• Chronic or acute oral inflammation at enrollment
• History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension
• Currently using any prohibited medication on the list of prohibited medication
• Part 1 and 2: Allergic symptoms in reaction to the placebo part of the screening DBPCFC Part 3: Dose-limiting allergic symptoms in reaction to the placebo part of the screening DBPCFC
• History of severe or life-threatening episode of anaphylaxis or anaphylactic shock within 60 days of the screening DBPCFC
• Part 1 and 2: Asthma according to below criteria:

• Severe asthma as per the current GINA guidelines
• Uncontrolled or poorly controlled asthma as per the current GINA guidelines
• Asthma that requires more than a daily dose above 800 µg of inhaled budesonide (or clinically comparable inhaled corticosteroids)
• History of 2 or more systemic corticosteroid courses within 6 months of screening
• Prior intubation/mechanical ventilation for asthma
• Emergency room visit or hospitalization for asthma in the 12 months prior to screening
• Any history of a life-threatening asthma attack
• Part 3: Asthma fulfilling the below criteria:

• History of 2 or more systemic corticosteroid courses within 6 months of screening
• Prior intubation/mechanical ventilation for asthma
• Emergency room visit or hospitalization for asthma in the 12 months prior to screening
• Any history of a life-threatening asthma attack
• (US only) Severe asthma as per the current GINA guidelines
• (US only) Uncontrolled or poorly controlled asthma as per the current GINA guidelines
• (US only) Asthma that requires more than a daily maintenance dose above 800 μg of inhaled budesonide (or clinically comparable inhaled corticosteroids)