Peanut Oral Immunotherapy in Children (IMPACT)

• ClinicalTrials.gov Identifier: NCT01867671
• Recruitment Status: Completed
• First Posted: June 4, 2013
• Results First Posted: January 22, 2020
• Last Update Posted: March 16, 2020
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Immune Tolerance Network (ITN)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information

• First Submitted Date: May 23, 2013
• First Posted Date: June 4, 2013
• Results First Submitted Date: December 20, 2019
• Results First Posted Date: January 22, 2020
• Last Update Posted Date: March 16, 2020
• Actual Study Start Date: August 13, 2013
• Actual Primary Completion Date: July 2, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 10, 2020)

Percentage of Participants Desensitized to Peanut Protein After 134 Weeks of Oral Immunotherapy (OIT) [ Time Frame: Week 134 ]

Definition of desensitized to peanut: A participant who passed the blinded (masked) oral food challenge (OFC) to10 grams of peanut flour (=5 grams of peanut protein) without significant symptoms.* *Significant symptoms include hives, wheezing, vomiting, or laryngeal edema.

Original Primary Outcome Measures (submitted: May 29, 2013)

Proportion of Desensitized Subjects [ Time Frame: week 134 ]

Participants who pass an oral food challenge (OFC) to 10 g of peanut flour (5 g of peanut protein) at this time without significant symptoms will be considered desensitized to peanut. Failure will be defined as either unable to undergo the final food challenge or inability to tolerate the maximum dose because of significant symptoms such as hives, wheezing, vomiting, or laryngeal edema.

Current Secondary Outcome Measures (submitted: February 26, 2020)

• Percentage of Tolerant Participants at Week 160 [ Time Frame: Week 160 ]
  Definition of Tolerant: A participant who passed the oral food challenge (OFC) to 10 grams of peanut flour (=5 grams of peanut protein).
• Count of Participants With Transient Desensitization [ Time Frame: Week 134, Week 160 ]
  Definition of transient desensitization: A participant who passed the blinded (masked) oral food challenge (OFC) to 10 grams peanut flour (=5 grams peanut protein) at week 134 and failed the week 160 in the Peanut oral immunotherapy (OIT) group.
• Highest Tolerated Cumulative Dose [ Time Frame: Week 160 ]
  The highest tolerated cumulative dose of peanut protein during the blinded (masked) oral food challenge (OFC) at Week 160, analyzed within and between both placebo and peanut OIT groups. The highest cumulative dose of peanut protein tolerated for each participant was analyzed as a continuous outcome. Any randomized participant without an evaluable blinded (masked) OFC was imputed as not tolerant. For the continuous highest cumulative dose endpoint, this is defined as having a highest cumulative dose imputed as zero.
• Percentage of Participants That Withdrew From the Study [ Time Frame: Initial Dose Escalation through Week 160 (Tolerance Assessment) ]
  Percentage of participants that withdrew from study participation, listed by study phase (at time of study withdrawal).

Original Secondary Outcome Measures (submitted: May 29, 2013)

• Tolerance Endpoint [ Time Frame: week 160 ]
  The proportion of participants who pass the OFC to 10 g peanut flour (5 g peanut protein).
• Transient Desensitization [ Time Frame: week 134 to week 160 ]
  The change in proportion of participants who pass the OFC to 10 g peanut flour (5 g peanut protein)at week 134 and week 160.
• Highest Tolerated Cumulative Dose [ Time Frame: week 160 ]
  The highest tolerated cumulative dose of peanut protein during the OFCs.
• The incidence of all adverse events [ Time Frame: week 160 ]
• Rates of Withdrawal from OIT or Placebo [ Time Frame: week 160 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Peanut Oral Immunotherapy in Children
• Official Title: Oral Immunotherapy for Induction of Tolerance and Desensitization in Peanut-Allergic Children (ITN050AD)
• Brief Summary: This is a randomized, double-blind, placebo-controlled, multi-center study comparing peanut oral immunotherapy (OIT) to placebo in the induction of tolerance and desensitization in peanut-allergic children. Eligible participants with peanut allergy will be randomly assigned to receive either peanut OIT or placebo for 134 weeks followed by peanut avoidance for 26 weeks.

Detailed Description

An initial oral food challenge (OFC) to 1 g of peanut flour (500 mg peanut protein) will be conducted. Participants must have a clinical reaction during this OFC to initiate study dosing. After the initial OFC, the study design includes four phases:

• Initial dose escalation (1 day): Peanut or placebo dosing will be given incrementally and increase every 20 minutes until a dose of 12 mg peanut flour (6 mg peanut protein) or placebo flour is given.
• Build-up (30 weeks): Initial observed dose administration of highest tolerated dose, followed by daily OIT at home with return visit every 2 weeks for dose escalation.
• Maintenance (104 weeks):The participant will continue on daily OIT with return visits every 13 weeks. At the end of this phase the participant will undergo a blinded OFC to 10 g peanut flour (5 g peanut protein).
• Avoidance (26 weeks): In this final phase participants will be seen every 13 weeks. At the completion of this phase participants will have a final blinded OFC to 10g peanut flour (5 g peanut protein).

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Peanut Hypersensitivity

Intervention

• Biological: Peanut Oral Immunotherapy - Liquid Extract
  Used during initial dose escalation for doses 0.1 to 0.8 mg.
• Biological: Placebo for Peanut Oral Immunotherapy - Liquid Extract form
  Similar in appearance, texture, and taste to peanut liquid extract.
• Biological: Peanut Oral Immunotherapy - Peanut Flour
  This will be used for the remainder of dose escalation, build-up, and maintenance.
• Biological: Placebo for Peanut Oral Immunotherapy - Peanut Flour
  Similar in appearance, texture, and taste to peanut flour.

Study Arms

• Experimental: Peanut Oral Immune Therapy (OIT)
  Peanut OIT for 134 weeks followed by peanut avoidance for 26 weeks.
  Interventions:

  • Biological: Peanut Oral Immunotherapy - Liquid Extract
  • Biological: Peanut Oral Immunotherapy - Peanut Flour
• Placebo Comparator: Peanut Placebo
  Peanut placebo for 134 weeks followed by peanut avoidance for 26 weeks. The placebo extract will be derived from oat flour source material.
  Interventions:

  • Biological: Placebo for Peanut Oral Immunotherapy - Liquid Extract form
  • Biological: Placebo for Peanut Oral Immunotherapy - Peanut Flour

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 9, 2015): 146
• Original Estimated Enrollment (submitted: May 29, 2013): 144
• Actual Study Completion Date: December 21, 2018
• Actual Primary Completion Date: July 2, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Clinical history of peanut allergy or avoidance of peanut without ever having eaten peanut;
• Serum immunoglobulin E (IgE) to peanut of ≥5 kUA/L determined by UniCAP™, an in-vitro test system for diagnosis and monitoring of allergy and inflammation;
• Wheal ≥ 3mm on skin prick test to peanut extract compared to a negative control;
• A clinical reaction at or below ingestion of 1 g peanut flour (500 mg peanut protein) during screening OFC;
• Written informed consent from parent/guardian.

Exclusion Criteria:

• History of severe anaphylaxis with hypotension to peanut;
• Documented clinical history of allergy to oat;
• Suspected allergy to oat and a wheal ≥7mm on skin prick test to oat extract compared to a negative control;
• Chronic disease other than asthma, atopic dermatitis, rhinitis requiring therapy; e.g., heart disease or diabetes;
• Active eosinophilic gastrointestinal disease in the past 2 years;
• Participation in any interventional study for the treatment of food allergy in the 6 months prior to visit -1;
• Inhalant allergen immunotherapy that has not yet reached maintenance dosing;
• Severe asthma, as indicated by repeated hospitalizations or hospital emergency department visits;
• Moderate asthma defined according to National Asthma Education and Prevention Program Expert;
• Panel that requires more than fluticasone 440 mcg or its equivalent daily for adequate control;
• Inability to discontinue antihistamines for skin testing, OFC and the initial dose escalation;
• Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) in the 12 months prior to visit -1;
• Any systemic therapy which in the judgment of the investigator could be immunomodulatory (e.g. rituximab) in the 12 months prior to visit -1, systemic corticosteroid therapy of up to a total of three weeks is allowed;
• Use of any investigational drug in 90 days prior to visit -1;
• Plan to use any investigational drug during the study period;
• The presence of any medical condition that the investigator deems incompatible with participation in the trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Months to 48 Months (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01867671
• Other Study ID Numbers: DAIT ITN050AD
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Responsible Party: Same as current
• Current Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Study Sponsor: Same as current
• Collaborators: Immune Tolerance Network (ITN)

Investigators

• Study Chair: Wesley Burks, MD; UNC Chapel-Hill
• Study Chair: Stacie M. Jones, MD; University of Arkansas

• PRS Account: National Institute of Allergy and Infectious Diseases (NIAID)
• Verification Date: February 2020