peanut sublingual immunotherapy (slit)-tablet for treatment of peanut allergy

Conditions: Peanut Allergy

Summary: this clinical research study investigates the safety, tolerability and efficacy of a peanut slit-tablet in adults, adolescents, and children with 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.

Eligibility criteria:
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)

Keywords: peanut allergy children adolescent adult