Peanut Allergy
Conditions
Keywords
Peanut allergy, Children, Adolescent, Adult
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.
Interventions
BIOLOGICALPeanut SLIT-tablet
Peanut extract
OTHERPlacebo
Placebo
Sponsors
ALK-Abelló A/S
Parexel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part 1 and 2 is open label. Part 3 is blinded.
Intervention model description
Part 1 and 2 is sequential Part 3 is parallel
Eligibility
Sex/Gender
ALL
Age
4 Years to 65 Years
Healthy volunteers
No
Inclusion 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 3: TD-600 response rate | After 24 weeks of maintenance treatment, up to 48 weeks. | The TD (tolerated dose)-600 response rate is defined as the percentage of subjects able to consume 600 mg (1044 mg cumulative) peanut protein without dose-limiting symptoms at the exit double-blind placebo-controlled food challenge (DBPCFC) after 24 weeks of maintenance treatment. Subjects that do not complete the exit DBPCFC are classified as non-responders. |
| Part 1 and 2: Dose tolerability response rate | 2 weeks per dose | The dose tolerability response rate is defined as the percentage of subjects who experience at most moderate local application site reactions after the last peanut SLIT-tablet intake of the dose step. Local application site reactions are treatment-related adverse events occurring in close proximity to the application site of the SLIT-tablet with a temporal relationship to tablet administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 3: Maximum severity of symptoms at each challenge dose of peanut protein during DBPCFC | At screening, 1 - 3 weeks, and after 24 weeks of maintenance treatment, up to 48 weeks. | The highest severity of any symptom experienced at any challenge dose during the DBPCFC. Possible values are 0=none, 1=mild, 2=moderate or 3=severe. |
| Part 3: Response rate - use of epinephrine as rescue medication during exit DBPCFC | After 24 weeks of maintenance treatment, up to 48 weeks. | The response rate is defined as the percentage of subjects that receive epinephrine as rescue medication during the exit DBPCFC. |
| Part 1, 2 and 3: Treatment-emergent adverse events | 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. | An adverse event is any untoward medical occurrence in a clinical trial subject and which does not necessarily have a causal relationship with the administered investigational medicinal product (IMP). A treatment-emergent adverse event has a start date on or after the time of first IMP intake and no later than 7 days after the last IMP intake. |
| Part 3: TD-300 response rate | After 24 weeks of maintenance treatment, up to 48 weeks. | The TD-300 response rate is defined as the percentage of subjects able to consume 300 mg (444 mg cumulative) peanut protein without dose-limiting symptoms at the exit DBPCFC after 24 weeks of maintenance treatment. Subjects that do not complete the exit DBPCFC are classified as non-responders. |
| Part 3: TD-2000 response rate | After 24 weeks of maintenance treatment, up to 48 weeks. | The TD-2000 response rate is defined as the percentage of subjects able to consume 2000 mg (4044 mg cumulative) peanut protein without dose-limiting symptoms at the exit DBPCFC after 24 weeks of maintenance treatment. Subjects that do not complete the exit DBPCFC are classified as non-responders. |
| Part 3: TD-1000 response rate | After 24 weeks of maintenance treatment, up to 48 weeks. | The TD-1000 response rate is defined as the percentage of subjects able to consume 1000 mg (2044 mg cumulative) peanut protein without dose-limiting symptoms at the exit DBPCFC after 24 weeks of maintenance treatment. Subjects that do not complete the exit DBPCFC are classified as non-responders. |
| Part 3: Maximum tolerated dose of peanut protein during DBPCFC | At screening, 1 - 3 weeks, and after 24 weeks of maintenance treatment, up to 48 weeks. | The highest single challenge dose of peanut protein that a subject can consume without experiencing dose-limiting symptoms during the DBPCFC. |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATOREdwin Kim, MD
University of North Carolina
Outcome results
None listed