Sublingual Immunotherapy for Peanut Allergy and Induction of Tolerance

NCT01373242 | Completed Phase 1 Results DMC

• 2 other identifiers: 11-23085R01AT004435-09
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study will be to increase the reaction threshold (desensitization) of peanut allergic children using peanut sublingual immunotherapy and to determine if the nonreactive state of the immune system persists after treatment has been discontinued (tolerance).

Conditions

Peanut Hypersensitivity; Food Hypersensitivity; Food Allergy; Peanut Allergy

Outcome Measures

Primary Outcomes (5)

• Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 5% of the Peanut-allergic Population

  An estimate of the dose as assessed by the 48th month DBPCFC reported in mg peanut protein, also called population sensitization threshold, predicted to provoke reactions in 5% of the peanut-allergic population. This will also give population level no observed adverse event level (NOAEL) and lowest observed adverse event level (LOAEL) that would define interval of consecutive administered dose levels within which the population sensitization threshold lies. NOAEL is the highest dose observed not to produce any adverse effect and LOAEL is the lowest dose that is observed to produce an adverse effect.

  48 - 52 months

• Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 10% of the Peanut-allergic Population

  An estimate of the dose as assessed by the 48th month DBPCFC reported in mg peanut protein, also called population sensitization threshold, predicted to provoke reactions in 10% of the peanut-allergic population. This will also give population level no observed adverse event level (NOAEL) and lowest observed adverse event level (LOAEL) that would define interval of consecutive administered dose levels within which the population sensitization threshold lies. NOAEL is the highest dose observed not to produce any adverse effect and LOAEL is the lowest dose that is observed to produce an adverse effect.

  48-52 months

• Population Estimate of Time for a Subject's True Sensitivity Threshold to Reduce by Half.

  A population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to reduce by half, also called half-life of sensitivity threshold. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data.

  52 months

• Population Estimate of a Subject's True Sensitivity Threshold to Maintain at the Same Dose Level During DBPCFC

  A population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to maintain at the same dose level during the double-blind, placebo-controlled food challenge. Food challenge dose levels are as follows: 100 mg, 200 mg, 500 mg, 800 mg, 1300 mg, 2100 mg. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data.

  52 months

• Population Estimate of a Subject's True Sensitivity Threshold to Decrease by One Dose Level of During the DBPCFC

  A population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to decrease by one dose level during the double-blind, placebo-controlled food challenge. Food challenge dose levels are as follows: 100 mg, 200 mg, 500 mg, 800 mg, 1300 mg, 2100 mg. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data.

  52 months

Secondary Outcomes (5)

• Number of Participants With Adverse Events and Serious Adverse Events During the Study.

  48 months

• Number of Participants With Gastrointestinal and Possible Gastrointestinal Eosinophilic Adverse Events.

  48 months

• Change in Peanut Skin Test Wheal Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed

  48 months

• Change in Peanut IgE Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed

  48 months

• Change in Peanut IgG4 Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed

  48 months

Study Arms (1)

Peanut ( liquid peanut extract) SLIT

EXPERIMENTAL

All subjects will receive peanut SLIT upon enrollment for at least the first 48 months. After the desensitization DBPCFC after at least 48 months of treatment, subjects will be randomized off treatment from 1 to 17 weeks. Subjects will then undergo another DBPCFC.

Drug: Liquid peanut extract (Peanut SLIT)

Interventions

Liquid peanut extract (Peanut SLIT) DRUG

Liquid peanut extract will be administered under the tongue

Also known as: Peanut SLIT - active arm

Peanut ( liquid peanut extract) SLIT

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Between ages 1 year to 12 years exclusive
• Peanut specific IgE \> 0.35kU/L or a convincing clinical history of an allergic reaction to peanut within 1 hour of ingestion
• Positive entry DBPCFC to 1 gram of peanut protein

You may not qualify if:

• History of severe anaphylaxis to peanut, defined as hypoxia, hypotension, or neurologic compromise (cyanosis or oxygen saturations \< 92% at any stage, hypotension, confusion, collapse, loss of consciousness, or incontinence)
• Participation in any interventional study for the treatment of food allergy in the past 6 months
• Known oat, wheat, or glycerin allergy
• Eosinophilic or other inflammatory (e.g. celiac) gastrointestinal disease
• Severe asthma (2007 National Heart Lung and Blood Institute (NHLBI) guidelines Criteria Steps 5 or 6 - Appendix 2)
• Inability to discontinue antihistamines for skin testing and DBPCFCs
• Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immunomodulator therapy (not including corticosteroids) or biologic therapy within the past year
• Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers
• Significant medical condition (e.g., liver, kidney, gastrointestinal, cardiovascular, hematologic, or pulmonary disease) which would make the subject unsuitable for induction of food reactions

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Peanut Hypersensitivity; Food Hypersensitivity

Condition Hierarchy (Ancestors)

Nut and Peanut Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Edwin Kim, MD; Director UNC Food Allergy Initiative
• Organization: University of North Carolina at Chapel Hill

edwinkim@email.unc.edu

919-537-3193

Study Officials

• Wesley Burks, MD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2011
• First Posted: June 14, 2011
• Study Start: June 1, 2011
• Primary Completion: April 16, 2018
• Study Completion: April 16, 2018
• Last Updated: June 12, 2019
• Results First Posted: June 12, 2019

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)