Tolerance Following Peanut Oral Immunotherapy

NCT01750879 | Completed Phase 1 Results DMC

• 2 other identifiers: 2012P0021535U19AI095261-02
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The unifying objective of this project is to determine whether peanut oral immunotherapy (PN OIT) induced clinical tolerance in the context of food allergy is significantly associated with the expansion of a specific regulatory T cell subset (CD45RA- CD25++ FoxP3++) that is thought to be inducible in the gut-associated lymphoid compartment and associated with immunological tolerance. The hypothesis of the study is that the induction of Treg cells will be associated with clinical tolerance. The investigators will measure the change from baseline of induced Treg cells as a frequency of total CD4 T cells during active treatment and compare that between participants who achieve significant clinical tolerance (Tolerance and Partial Tolerance Groups as defined below) and those who do not (Treatment Failure Group).

Conditions

Peanut Allergy

Keywords

peanut; allergy; food; immunotherapy; tolerance; desensitization

Outcome Measures

Primary Outcomes (1)

• Tolerance, Partial Tolerance, or Treatment Failure

  1. Tolerance: Ingestion of 4430 mg of peanut protein at DBPCFC3 without symptoms. 2. Partial Tolerance: ED at DBPCFC3 \<4430 mg but =\>430 mg AND \>10-fold more than at DBPCFC1. 3. Treatment Failure - non desensitized: Failure to achieve the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED \<1443 mg at DBPCFC2, or ED at DBPCFC3 \<443 mg OR \<10-fold more than at DBPCFC1. 4. Treatment Failure - withdrawal

  Average 515 days from DBPCFC1 to DBPCFC3

Secondary Outcomes (8)

• Clinical: Tolerance

  630 days

• Clinical: Desensitization

  518 days

• Clinical: Safety

  630 days

• Mechanistic: TCR Clonal Diversity

  630 days

• Mechanistic: Change Eliciting Dose of End-point Dilution.

  518 days

Study Arms (2)

Peanut Flour

ACTIVE COMPARATOR

Oral Immunotherapy with peanut flour.

Drug: Peanut Flour

Oat Flour

PLACEBO COMPARATOR

Oral Immunotherapy with oat flour.

Drug: Oat Flour

Interventions

Peanut Flour DRUG

Peanut Flour

Peanut Flour

Oat Flour DRUG

Oat Flour

Oat Flour

Eligibility Criteria

• Age: 7 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of peanut allergy by a positive skin prick test to peanut (reaction wheal at least 5 mm larger than saline control) and by medical history or Serum peanut-specific IgE \>5 kU/L at screening visit.
• Ara h 2 specific IgE \>0.35 kU/L at screening visit
• Ability to provide informed consent.
• Males and females of all ethnic/racial groups aged 7-55 years old who are otherwise healthy.
• React to less than 443 mg of peanut protein during DBPCFC1

You may not qualify if:

• History of severe anaphylaxis as defined by hypoxia (cyanosis or SpO2 \<92% during reaction), documented hypotension (documented systolic BP \>30% below predicted normal for sex, height, weight or from known baseline), neurological compromise (confusion, loss of consciousness), or incontinence.
• Severe or Moderate asthma as defined using the severity criteria of the current NHBLI Guidelines for the Diagnosis and Management of Asthma (http://www.nhlbi.nih.gov/guidelines/asthma/).
• Poorly-controlled asthma as defined by FEV1 \<80% or any of the following symptoms: nighttime awakening \>2 days/week or rescue medication use \>2 days / week.
• Diagnosis of other severe or complicating medical problems, including autoimmune or chronic immune inflammatory conditions or gastrointestinal inflammatory conditions, including Celiac Disease, Inflammatory Bowel Disease and Eosinophilic Gastrointestinal Disorders
• Inability to cooperate with and/or perform oral food challenge procedures.
• Primary Immune Deficiency
• Allergy to oat confirmed by skin prick testing and history
• Current use of beta blockers, angiotensin converting enzyme inhibitors, or monoamine oxidase inhibitors
• Women of childbearing potential who are pregnant, planning to become pregnant, or breastfeeding
• Hemoglobin level less than 12.5 gm/dL at screening. Weight \<23 kg
• Use within the past 6 months of other systemic immunomodulatory treatments including allergen immunotherapy, or use of biologics with an immune target, including omalizumab.
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study may also exclude a participant from the study.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Monian B, Tu AA, Ruiter B, Morgan DM, Petrossian PM, Smith NP, Gierahn TM, Ginder JH, Shreffler WG, Love JC. Peanut oral immunotherapy differentially suppresses clonally distinct subsets of T helper cells. J Clin Invest. 2022 Jan 18;132(2):e150634. doi: 10.1172/JCI150634.

  PMID: 34813505 DERIVED

MeSH Terms

Conditions

Peanut Hypersensitivity; Hypersensitivity

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Wayne Shreffler
• Organization: Massachusetts General Hospital

WSHREFFLER@mgh.harvard.edu

617-726-6147

Study Officials

• Wayne G Shreffler, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 13, 2012
• First Posted: December 17, 2012
• Study Start: August 1, 2013
• Primary Completion: July 11, 2017
• Study Completion: July 11, 2017
• Last Updated: July 28, 2021
• Results First Posted: July 28, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: upon request within the year and without planned time limitation

Locations

US (1)