FARE Peanut SLIT and Early Tolerance Induction (FARE/SLIT)

• ClinicalTrials.gov Identifier: NCT02304991
• Recruitment Status: Completed
• First Posted: December 2, 2014
• Results First Posted: December 16, 2021
• Last Update Posted: January 10, 2022
• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Food Allergy Research & Education; National Center for Complementary and Integrative Health (NCCIH); University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

Tracking Information

• First Submitted Date: November 21, 2014
• First Posted Date: December 2, 2014
• Results First Submitted Date: November 17, 2021
• Results First Posted Date: December 16, 2021
• Last Update Posted Date: January 10, 2022
• Actual Study Start Date: January 2015
• Actual Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 17, 2021)

Desensitization After 36 Months of Peanut SLIT or Placebo SLIT [ Time Frame: 36 months ]

The primary outcome of this study will be a statistically significant difference in the challenge score of the treatment group versus the placebo group during DBPCFC after 36 months of peanut SLIT (desensitization). DBPCFC Challenge Score scale: Minimum score = 0; Maximum score = 7 Larger challenge score equals more successful desensitization. 0mg = 0; 3mg = 1; 13mg = 2; 43mg = 3; 143mg = 4; 443mg = 5; 1443mg = 6; and 4443mg = 7.

Original Primary Outcome Measures (submitted: November 26, 2014)

Percentage of participants desensitized to peanut using peanut SLIT as an early intervention in subjects ages 1 to 4 years [ Time Frame: From baseline to 36 months ]

The primary outcome is to detect a statistically significant difference in reaction thresholds to peanut between the treatment group versus the placebo group during DBPCFC (Double blind placebo controlled food challenge) performed after 36 months of peanut SLIT (desensitization). A secondary outcome of this objective is to detect a statistically significant difference between reaction thresholds to peanut of the treatment group versus the placebo group during the DBPCFC performed 3 months after discontinuing therapy (tolerance). Challenge scores are measured by the amount of peanut protein participants are able to ingest successfully without symptoms of an allergic reaction. The difference is measured through utilization of an extreme value hazard function.

Current Secondary Outcome Measures (submitted: November 17, 2021)

• Tolerance 3 Months After Discontinuing Peanut SLIT or Placebo SLIT [ Time Frame: 39 months ]
  A secondary outcome of this study will be a statistically significant difference in the challenge score of the treatment group versus the placebo group during the DBPCFC performed 3 months after discontinuing therapy (tolerance). DBPCFC Challenge Score scale: Minimum score = 0; Maximum score = 7 Larger challenge score equals more successful desensitization. 0mg = 0; 3mg = 1; 13mg = 2; 43mg = 3; 143mg = 4; 443mg = 5; 1443mg = 6; and 4443mg = 7.
• Change in Immune Parameters With Peanut SLIT Versus Placebo SLIT (Peanut-specific IgE) [ Time Frame: 0 months to 36 months ]
  The change in immune parameters over time associated with the induction of clinical desensitization compared to the failure to achieve clinical desensitization. Peanut-specific IgE measured at baseline and at completion of peanut SLIT (36 months). Change in IgE reported in kUA/L.
• Change in Immune Parameters With Peanut SLIT Versus Placebo SLIT (Peanut-specific IgG4) [ Time Frame: 0 months to 36 months ]
  The change in immune parameters over time associated with the induction of clinical desensitization compared to the failure to achieve clinical desensitization. Peanut-specific IgG4 measured at baseline and at completion of peanut SLIT (36 months). Change in IgG4 reported in mg/L.
• Change in Immune Parameters With Peanut SLIT Versus Placebo SLIT (Peanut Skin Prick Test) [ Time Frame: 0 months to 36 months ]
  The change in immune parameters over time associated with the induction of clinical desensitization compared to the failure to achieve clinical desensitization. Peanut-skin prick test measured at baseline and at completion of peanut SLIT (36 months). Change in skin prick test reported in mm wheal diameter.
• Number of Participants Experiencing Serious Adverse Events With Peanut SLIT Versus Placebo SLIT [ Time Frame: 39 months ]
  Incidence of all serious adverse events from initial enrollment through the end of the 3 month avoidance period reported as the number of participants experiencing a serious adverse event.

Original Secondary Outcome Measures (submitted: November 26, 2014)

• The change in peanut specific IgE levels [ Time Frame: From baseline to 36 months ]
  To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.
• The change in peanut specific IgG levels [ Time Frame: From baseline to 36 months ]
  To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.
• The change in peanut specific IgG4 levels [ Time Frame: From baseline to 36 months ]
  To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.
• The change in peanut specific basophil activation [ Time Frame: From baseline to 36 months ]
  To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.
• The change in responses of mast cell as measured by prick skin testing to peanut [ Time Frame: From baseline to 36 months ]
  To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.
• The change in specific T-cell cytokine responses [ Time Frame: From baseline to 36 months ]
  To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.
• The change in T regulatory cell activation [ Time Frame: From baseline to 36 months ]
  To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.

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

Descriptive Information

• Brief Title: FARE Peanut SLIT and Early Tolerance Induction
• Official Title: Peanut Sublingual Immunotherapy Induction of Clinical Tolerance of Newly Diagnosed Peanut Allergic 12 to 48 Month Old Children

Brief Summary

Primary Objective: To determine if 36 months of peanut SLIT as an early intervention in subjects ages 1 to 4 years induces clinical desensitization. The primary outcome of this objective will be a statistically significant difference in challenge scores between the treatment group versus the placebo group during DBPCFC (Double blind placebo controlled food challenge) performed after 36 months of peanut SLIT (desensitization). Challenge scores are measured by the amount of peanut protein participants are able to ingest successfully without symptoms of an allergic reaction. [Time Frame: Baseline, 36 months]

Secondary Objectives:

A secondary outcome of this objective will be a statistically significant difference in the challenge score of the treatment group versus the placebo group during the DBPCFC performed 3 months after discontinuing therapy (tolerance).

To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein.

[Time Frame: Baseline, 39 months]

Detailed Description

Peanut allergy is one of the most common food allergies; most children develop this allergy early in life, do not outgrow it and are at risk for severe and life-ending anaphylactic reactions. There is a critical need for a proactive treatment for peanut allergy and the investigators along with others are developing specific types of immunotherapy that will act as disease-modifying therapies.

This SLIT study is a randomized, blinded, placebo-controlled study. The primary outcome of this objective will be a statistically significant difference in challenge scores between the treatment group versus the placebo group during DBPCFC performed after 36 months of peanut SLIT (desensitization). A secondary outcome of this objective will be a statistically significant difference in the challenge score of the treatment group versus the placebo group during the DBPCFC performed 3 months after discontinuing therapy (tolerance).

Upon enrollment into the study, all subjects will undergo a qualifying entry DBPCFC with peanut protein to confirm the diagnosis of peanut allergy and establish a baseline threshold level. Following a positive DBPCFC, each subject will be randomized 1:1 to receive peanut SLIT therapy versus placebo for a duration of 36 months. DBPCFC will be repeated for both active and placebo subjects at 36 months to assess desensitization and at 39 months to assess tolerance.

Outcome variables of interest include peanut specific IgE, IgG, and IgG4, basophil activation, mast cell responses through skin prick testing, and specific T-cell cytokine responses and T regulatory cell (TReg) activation.

COVID-19 SAFETY MEASURES- Reflected in Protocol V4.0- April 2020

In March of 2020, State and National emergencies were declared over the global pandemic coronavirus COVID-19.

As such, any 36 month Desensitization DBPCFC will be postponed while the safety measures surrounding COVID-19 are in place. Subjects who choose to remain in the study will continue on study drug at the maintenance dose level beyond the originally planned 36 months until such time that the Desensitization DBPCFC is conducted.

Subjects who are scheduled to undergo the 39 month Tolerance DBPCFC while the COVID-19 safety measures are in place will have their DBPCFC cancelled. Additional time off of study drug therapy would potentially increase the risk of allergic reaction during the DBPCFC and would not be acceptable.

For subjects whose Desensitization DBPCFC is postponed, a followup visit to review safety and subject dosing diaries would be conducted. This visit would be conducted remotely by telephone. Additional study drug would be sent direct-to-patient as necessary to continue on maintenance dosing. Lab sample collection and mechanistic studies would be deferred and be completed at the time that the Desensitization DBPCFC is completed. The Tolerance DBPCFC would be completed 3 months after the Desensitization DBPCFC is completed.

For subjects whose Tolerance DBPCFC is canceled, an exit visit would be conducted to review safety. The subject would be unblinded to treatment allocation and end of study instructions would be reviewed with the subject.

As the situation is changing daily, we are unable to provide a time frame for extension. We hope to limit the number of subjects who will need to utilize this option and preserve the endpoint data parameters. Previous SLIT studies have not shown any additional risk with peanut SLIT dosing beyond 3 years up to a total of 5 years of dosing.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Peanut Hypersensitivity
• Food Allergy
• Food Hypersensitivity
• Peanut Allergy

Intervention

• Drug: Liquid Peanut Extract
  5000mcg/ml peanut protein
  Other Name: SLIT
• Drug: Placebo Glycerin SLIT
  pure glycerinated saline solution with caramel coloring to match color
  Other Name: SLIT

Study Arms

• Experimental: Peanut (liquid peanut extract) SLIT
  After the entry DBPCFC, subjects will be randomized 1:1 to active or placebo drug product. Subjects randomized to peanut SLIT therapy will dose for 36 months and undergo a second DBPCFC. The subjects will stop dosing for three months and repeat a DBPCFC at 39 months.
  Intervention: Drug: Liquid Peanut Extract
• Placebo Comparator: Placebo Glycerin SLIT
  After the entry DBPCFC, subjects will be randomized 1:1 to active or placebo drug product. Subjects randomized to placebo glycerin SLIT will dose for 36 months and undergo a second DBPCFC. The subjects will stop dosing for three months and repeat a DBPCFC at 39 months.
  Intervention: Drug: Placebo Glycerin SLIT

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 26, 2014): 50
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 31, 2020
• Actual Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Written informed consent from participant's parent/guardian.
• Age 12-48 months of either sex, any race, any ethnicity.
• A peanut allergy diagnosis with a convincing clinical history of peanut allergy and a serum peanut-specific IgE [UniCAP] > 0.35 kUA/L AND a positive skin prick test to peanut (>3 mm than the negative control) OR are sensitized to peanut (based on a serum IgE [UniCAP] to peanut of > 5 kUA/L) AND a positive skin prick test to peanut (> 3 mm than the negative control) and no known history of ingestion of peanut.
• A positive DBPCFC to 1000 mg of peanut at enrollment.

Exclusion Criteria:

• History of severe anaphylaxis to peanut, defined as hypoxia, hypotension, or neurologic compromise (cyanosis or peripheral capillary oxygen saturation (SpO2) < 92% at any stage, hypotension, confusion, collapse or loss of consciousness).
• 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 NHLBI 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.

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: NCT02304991
• Other Study ID Numbers: 14-0648; R01AT004435-07 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of North Carolina, Chapel Hill
• Original Responsible Party: Wesley Burks, MD, University of North Carolina, Chapel Hill, Chairman, Department of Pediatrics
• Current Study Sponsor: University of North Carolina, Chapel Hill
• Original Study Sponsor: Same as current

Collaborators

• Food Allergy Research & Education
• National Center for Complementary and Integrative Health (NCCIH)
• University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: Wesley Burks, MD; University of North Carolina, Chapel Hill

• PRS Account: University of North Carolina, Chapel Hill
• Verification Date: January 2021