Evaluating the Safety and Efficacy of Oral Encapsulated Microbiota Transplantation Therapy in Peanut Allergic Patients

A Phase II Trial to Evaluate the Safety and Efficacy of Oral Encapsulated Microbiota Transplantation Therapy in Peanut Allergic Patients

This is a phase II randomized double-blind placebo-controlled trial that aims at evaluating the safety and tolerability of oral encapsulated fecal microbial transplantation therapy (MTT) in peanut allergic patients. In this research the investigators would like to learn more about ways to treat peanut allergies. The primary objective is to evaluate whether MTT with antibiotic pretreatment can increase the threshold of peanut reactivity during a double-blind placebo-controlled food challenge from <=100 mg peanut protein to 300 mg after 28 days of MTT /placebo therapy and 4 months post therapy initiation.

Study Overview

• Status: Recruiting
• Conditions: Peanut Hypersensitivity; Peanut Allergy; Food Allergy; Food Allergy Peanut; Peanut-Induced Anaphylaxis; Allergy, Peanut
• Intervention / Treatment: Biological: Microbial Transplantation Therapy; Drug: Antibiotic; Other: Placebo (in place of MTT); Other: Placebo (in place of antibiotics)

Detailed Description

This is a phase II randomized double-blind placebo-controlled trial that aims at evaluating the safety and tolerability of oral encapsulated fecal microbial transplantation therapy (MTT) in 24 peanut allergic patients, 12-17 years of age. After reacting to <=100 mg peanut protein during initial DBPCFC, patients will be randomized to receive either oral Vancomycin and Neomycin or placebo/placebo for 7 days. Patients will then come to the Experimental and Therapeutic Unit (ETU) to receive orally 5 capsules of MTT or placebo under medical supervision. Patients will then take 2 capsules of MTT or placebo daily for 27 days. Patients will return to the ETU to undergo a second DBPCFC within 2 weeks of end of MTT/placebo treatment and 4 months post MTT initiation. They will return to the ETU for an exit visit 6 months after end of treatment. Gut microbiota will be analyzed serially using state-of-the-art 16SRNA sequencing prior to transplantation, then at 4 weeks, 4-month, and 6 months post transplantation. Immunological biomarkers and mechanistic studies will be performed on blood taken at baseline, second DBPCFC visit and exit visit. Adverse events will be monitored carefully throughout the study.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Angela Zhang; Phone Number: 617-919-1566; Email: Angela.Zhang@childrens.harvard.edu
• Study Contact Backup: Name: Ghinwa Al Hassanieh; Phone Number: 617-919-6041; Email: Ghinwa.AlHassanieh@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Angela Zhang; Phone Number: 617-919-1566; Email: Angela.Zhang@childrens.harvard.edu
      • Contact: Farida Abi Farraj; Phone Number: 617-919-6041; Email: Farida.AbiFarraj@childrens.harvard.edu
      • Principal Investigator: Rima Rachid, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Develop dose limiting symptoms to peanut during a DPBCFC conducted in accordance with PRACTALL (Practical Issues in Allergology, Joint United States/European Union Initiative) guidelines at 1 mg, 3 mg, 10 mg, 30 mg, or 100 mg peanut protein.
2. Has a positive SPT to peanut (≥3mm) and/or a positive peanut-specific IgE >0.35kU/L.
3. For asthmatic patients, has a Spirometry or Peak Flow with Measurement of FEV1>=80% of predicted
4. Has a negative urine hCG test if a female participant.
5. Agrees to use an acceptable single-barrier form of birth control from enrollment through the exit DBPCFC study visit if female of childbearing potential and sexually active. An example of a single-barrier method of contraception includes condoms or oral contraceptives. Acceptable methods of birth control include implants, injectables, combined oral contraceptives, some intrauterine contraceptive devises (IUDs), sexual abstinence, a vasectomized partner, the contraceptive patch, the contraceptive ring, and condoms.
6. Able to swallow 2 empty capsules size 00.
7. Able to give informed assent and guardian willing to give informed consent.
8. Willing and able to participate in the study requirements, including study visits, DBPCFCs, serial stool collection
9. Willing to undergo telephone or email follow-up to assess for safety and adverse events.

Exclusion Criteria:

1. Patients with a history of severe anaphylaxis to any food (hypotension requiring vasopressor support, hypoxia requiring mechanical ventilation, or neurological compromise)
2. Patients with a history of IgE mediated reactions to food (excluding allergic reactions to peanut, tree nuts, egg and milk, provided that MTT does not contain traces of these l food estimated to be above the LOAEL in 5 capsules combined, and excluding oral allergy syndrome).
3. Patients with chronic illness other than controlled asthma that is mild intermittent, mild- persistent or moderate persistent, mild eczema and allergic rhinitis. Exceptions can be made per PI discretion if illness is not expected to affect allergies or treatment.
4. Recurrent or chronic infections necessitating frequent systemic (including oral) antibiotic administration.
5. Patients on chronic systemic immunosuppressive therapies.
6. Patients who are diagnosed with active, chronic urticaria.
7. Patients who have received peanut oral immunotherapy within the past 6 months.
8. Patients who are on the up-dosing phase of aeroallergen immunotherapy or patients who have received Omalizumab or dupilumab therapy within the past 6 months.
9. Women who are pregnant or breast feeding or planning to get pregnant during the time of the study.
10. Sexually active female patients who refuse to use contraception from enrollment through the third DBPCFC study visit
11. Patient with GI conditions including inflammatory bowel disease, eosinophilic esophagitis, food protein induced enterocolitis, uncontrolled reflux despite medication, uncontrolled chronic constipation despite medication, esophageal dysmotility, swallowing dysfunction, delayed gastric emptying syndromes, pill esophagitis or history of aspiration pneumonia within 3 months prior to screening.
12. Patient with current rheumatologic conditions. Exceptions can be made per PI discretion if illness is not expected to affect allergies or treatment.
13. Patients with neutropenia <1000 unit of measure?
14. Patients participating or planning to participate in the next 6 months in interventional research trials. Exceptions can be made per PI discretion.
15. Patients who have received systemic corticosteroids therapy for 1 week or more over the past 2 months.
16. Patient with an allergy to Vancomycin or Neomycin

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: antibiotic / MTT; Study subjects randomized to the experimental arm will receive oral antibiotics for 7 days as a way to modulate the composition of the gastrointestinal microbiota. Upon completion of oral antibiotics, subjects randomized to the experimental arm will be administeredf MTT under medical supervision. Subjects will be monitored and then discharged. Subjects will be instructed to take MTT capsules daily for 27 days.	Biological: Microbial Transplantation Therapy; Subjects randomized to the MTT/antibiotic arm will be administered oral MTT capsules over the course of 28 days.; Drug: Antibiotic; Subjects randomized to the MTT/antibiotic arm will receive oral antibiotics for 7 days prior to the MTT administration visit.
Active Comparator: placebo / placebo; Study subjects randomized to the placebo arm will receive oral placebo capsules instead of oral antibiotics, for 7 days, at the same frequency and capsule amount per dose. Upon completion of 7 days of placebo (matching the antibiotics given in the experimental arm), subjects randomized to the placebo arm will be administered capsules of placebo (matching the MTT capsules given in the experimental arm) under medical supervision. Subjects will be monitored and then discharged. Subjects will be instructed to take placebo capsules daily for 27 days.	Other: Placebo (in place of MTT); Subjects randomized to the placebo arm will be administered oral placebo capsules in place of MTT over the course of 28 days.; Other: Placebo (in place of antibiotics); Subjects randomized to the placebo arm will receive oral placebo in place of antibiotics for 7 days prior to the MTT administration visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in threshold of peanut reactivity during DBPCFC (<=100 mg to 300 mg peanut protein)	Changes in threshold of peanut reactivity during DBPCFC after 28 days of MTT from <=100 mg to 300 mg peanut protein and 4 months post therapy initiation.	4 months post MTT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in threshold of peanut reactivity during DBPCFC (<=100 mg to 600 mg peanut protein)	Changes in threshold of peanut reactivity during DBPCFC after 28 days of MTT from <=100 mg to 600 mg peanut protein and 4 months post therapy initiation.	4 months post MTT
Adverse Events	MTT Treatment emergent adverse events	8 months
Changes in Skin Test Wheal Size and IgE level	Changes in skin test peanut specific wheal size, peanut-specific IgE level over time	8 months
Changes in Gut Microbial Composition	Changes in gut microbial composition and persistence of that change over time	8 months
Changes in Biomarkers	Changes in biomarkers including RoRgt+Treg cells and Th2 helper cells frequencies after MTT therapy	8 months

Collaborators and Investigators

• Sponsor: Rima Rachid
• Collaborators: University of Minnesota
• Investigators: Principal Investigator: Rima Rachid, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2023
• Primary Completion (Estimated): January 11, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: January 13, 2023
• First Submitted That Met QC Criteria: January 13, 2023
• First Posted (Actual): January 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Peanut Hypersensitivity; Food Hypersensitivity; Anaphylaxis; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: P00043954

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No