Clinical trial NCT05440643: Peanut Sublingual Immunotherapy (SLIT)-Tablet for Treatment of Peanut Allergy
Official title: A Phase I/II Trial in 3 Parts Assessing the Safety, Tolerability, and Efficacy of a Once-daily Peanut Sublingual Immunotherapy (SLIT) Tablet in Adults, Adolescents, and Children With Peanut Allergy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Peanut Allergy
Keywords: Peanut allergy
Children
Adolescent
Adult
Lead sponsor: ALK-Abelló A/S
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2022-07-01
Enrollment: 192
Sex: ALL
Minimum age (years): 4
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 and 2 is sequential Part 3 is parallel
Primary purpose: TREATMENT

Brief summary: This clinical research study investigates the safety, tolerability and efficacy of a peanut SLIT-tablet in adults, adolescents, and children with peanut allergy.

Detailed description: 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)

Primary outcomes:
measure: Part 1 and 2: Dose tolerability response rate
timeFrame: 2 weeks per dose
measure: Part 3: TD-600 response rate
timeFrame: After 24 weeks of maintenance treatment, up to 48 weeks.
Secondary outcomes:
measure: Part 1, 2 and 3: Treatment-emergent adverse events
timeFrame: Part 1 and 2: 2 weeks per dose; Part 3: from first IMP intake to 7 days after last IMP intake, up to 48 weeks.
measure: Part 3: TD-300 response rate
timeFrame: After 24 weeks of maintenance treatment, up to 48 weeks.
measure: Part 3: TD-1000 response rate
timeFrame: After 24 weeks of maintenance treatment, up to 48 weeks.
measure: Part 3: TD-2000 response rate
timeFrame: After 24 weeks of maintenance treatment, up to 48 weeks.
measure: Part 3: Maximum tolerated dose of peanut protein during DBPCFC
timeFrame: At screening, 1 - 3 weeks, and after 24 weeks of maintenance treatment, up to 48 weeks.
measure: Part 3: Maximum severity of symptoms at each challenge dose of peanut protein during DBPCFC
timeFrame: At screening, 1 - 3 weeks, and after 24 weeks of maintenance treatment, up to 48 weeks.
measure: Part 3: Response rate - use of epinephrine as rescue medication during exit DBPCFC
timeFrame: After 24 weeks of maintenance treatment, up to 48 weeks.
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles - USC School of Medicine
state: California
city: Los Angeles
country: United States
facility: UCLA - Pediatrics
state: California
city: Palo Alto
country: United States
facility: Stanford University - Lucile Packard Children's Hospital
state: California
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates (PRA)
state: California
city: San Diego
country: United States
facility: Eastern Virginia Medical School - Children's Hospital
state: California
city: Walnut Creek
country: United States
facility: Allergy & Asthma Clinical Research
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hialeah
country: United States
facility: Quality Research of South Florida
state: Florida
city: Tampa
country: United States
facility: MOORE-PH Dermatology - Clinical Research
state: Florida
city: Tampa
country: United States
facility: USF Asthma Allergy and Immunology Clinical Research Unit
state: Florida
city: Atlanta
country: United States
facility: Center for Advance Pediatrics
state: Georgia
city: Chicago
country: United States
facility: Ann Robert H. Lurie Childrens Hospital of Chicago
state: Illinois
city: Normal
country: United States
facility: Sneeze, Wheeze, & Itch Associates, LLC
state: Illinois
city: Louisville
country: United States
facility: Family Allergy Asthma Research Institute
state: Kentucky
city: Lafayette
country: United States
facility: Velocity Clinical Research - Lafayette
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: White Marsh
country: United States
facility: Asthma, Allergy and Sinus Center
state: Maryland
city: Boston
country: United States
facility: Boston Food Allergy Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: NYU Langone Health - Fink Children's Ambulatory Care Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mt. Sinai, Pediatric Allergy, Kravis Children Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Columbus
country: United States
facility: Aventiv research, Inc
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadephia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburg of UPMC - Immunology and Rheumatology
state: Pennsylvania
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: El Paso
country: United States
facility: Western Sky Medical Research
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine (BCM) Texas Children's Hospital Pediatrics and Immunology
state: Texas
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Colombia
city: Winnipeg
country: Canada
facility: The Children's Hospital Foundation of Manitoba
state: Manitoba
city: Burlington
country: Canada
facility: Halton Pediatric Allergy
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Allergy
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Allergy Research Corporation
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children, Toronto
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre (MUHC) - Research Institute (RI-MUHC)
state: Quebec
city: Montréal
country: Canada
facility: CHU-Saint-Justine
state: Quebec
city: Québec
country: Canada
facility: Clinique Specialisee en Allergie de la Capitale
Study officials:
affiliation: University of North Carolina
name: Edwin Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: