VE416 for Treatment of Food Allergy

VE416 and Low-dose Peanut Oral Immunotherapy for Treatment of Persistent Peanut Allergy

This is a single-center, randomized, double-blind trial with four arms evaluating VE416 as pretreatment or concurrent treatment in comparison to low-dose peanut oral immunotherapy (PNOIT) alone.

Study Overview

• Status: Recruiting
• Conditions: Peanut Allergy
• Intervention / Treatment: Combination product: Vancomycin plus VE416 before PNOIT; Combination product: Vancomycin plus VE416 with PNOIT; Combination product: Placebo plus VE416 with PNOIT; Combination product: Placebo plus placebo with PNOIT

Detailed Description

In this research study the investigators want to learn more about an investigational medicine called VE416 in combination with vancomycin (an antibiotic) while undergoing peanut oral immunotherapy. VE416 is a combination of dormant (inactive) bacteria given in a capsule. The bacteria are reactivated once they reach participants intestines and in combination with peanut flour may help to prevent participants from getting sick (upset stomach, breathing problems, and skin problems) when participants come into contact with peanuts.

The investigators are doing this research study to find out if VE416 in combination with vancomycin (an antibiotic) while undergoing peanut oral immunotherapy can help people with peanut allergy. VE416 is a consortium of commensal, or "friendly", dormant (inactive) bacteria given in a capsule. The bacteria are reactivated once they reach participants intestines. The investigators also want to find out if VE416 with peanut oral immunotherapy is safe to take without causing too many side effects.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Wayne G Shreffler, MD, PhD; Phone Number: 617-726-6147; Email: wshreffler@mgh.harvard.edu
• Study Contact Backup: Name: Jannat Gill, BDS, MPH; Phone Number: 617-643-8683; Email: jgill0@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Wayne G Shreffler, MD, PhD; Phone Number: 617-643-9089; Email: WSHREFFLER@mgh.harvard.edu
      • Contact: Jannat Gill, MPH; Email: jgill0@mgh.harvard.edu
      • Principal Investigator: Wayne G Shreffler, MD, PhD
      • Principal Investigator: Chen Rosenberg, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• People of all ethnic/racial/gender groups aged 12-55 years old with a documented medical history of peanut allergy.
• Evidence of peanut-specific IgE by either: positive skin prick test to peanut (reaction wheal at least 5 mm larger than saline control) or serum peanut-specific IgE _5 kU/L at screening visit.
• Ara h 2 specific IgE >0.35 kU/L at screening visit.
• Willing to sign informed consent or whose parent or legal guardian is willing to sign the consent form (age appropriate).
• Willing to sign the assent form, if age appropriate.
• (For continuation into Phase II only) Allergic reaction requiring treatment at _ 100 mg dose of peanut protein during Entry Challenge.

Exclusion Criteria:

• 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 NHLBI 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.
• Inability to swallow size 0 capsule
• 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
• Hematocrit <0.36 for adult females or <0.38 for adult males 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vancomycin plus VE416 before PNOIT; active vancomycin plus VE416 before PNOIT	Combination product: Vancomycin plus VE416 before PNOIT; Vancomycin PO QD x 5 days, followed by VE416 PO QD x 6 weeks followed by PNOIT
Experimental: Vancomycin plus VE416 with PNOIT; active vancomycin plus active VE416 with active PNOIT	Combination product: Vancomycin plus VE416 with PNOIT; Placebo for vancomycin for 5 days and placebo for VE416 x 6 weeks, followed by Vancomycin PO QD x 5 days, followed by VE416 PO QD x 6 weeks with concomitant PNOIT
Experimental: Placebo plus VE416 with PNOIT; placebo vancomycin plus active VE416 with active VE416	Combination product: Placebo plus VE416 with PNOIT; Placebo for vancomycin for 5 days and placebo for VE416 x 6 weeks, followed by placebo for vancomycin PO QD x 5 days, followed by VE416 PO QD x 6 weeks with concomitant PNOIT
Active Comparator: Placebo plus placebo with PNOIT; placebo vancomycin and placebo VE416 with active peanut oral immunotherapy	Combination product: Placebo plus placebo with PNOIT; Placebo for vancomycin for 5 days and placebo for VE416 x 6 weeks, followed by placebo for vancomycin PO QD x 5 days, followed by placebo for VE416 PO QD x 6 weeks with concomitant PNOIT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endpoint- Phase 1b	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	7 weeks
Primary Endpoint- Phase II	The geometric mean of the maximum tolerated dose (MTD) of peanut protein at DBPCFC1	23 weeks, with 24 week Post-Phase II maintenance phase followed by a DBPCFC

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Endpoint- Efficacy	The percentage of patients tolerating 600 mg (1030 mg cumulative) at DBPCFC1 without treatment	54 weeks
Secondary Endpoint- Safety	The occurrence of treatment related adverse events	54 weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Vedanta Biosciences, Inc.
• Investigators: Principal Investigator: Wayne G Shreffler, MD, PhD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Berin MC. Dysbiosis in food allergy and implications for microbial therapeutics. J Clin Invest. 2021 Jan 19;131(2):e144994. doi: 10.1172/JCI144994.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2019
• Primary Completion (Estimated): November 1, 2023
• Study Completion (Estimated): January 1, 2024

Study Registration Dates

• First Submitted: April 17, 2019
• First Submitted That Met QC Criteria: May 1, 2019
• First Posted (Actual): May 3, 2019

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Peanut Hypersensitivity; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: 2019P000886

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No