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

Part A is a This is a phase II randomized double-blind placebo-controlled arm trial that aims at evaluating the efficacy and safety and tolerability of microbial transplantation therapy (MTT) in peanut allergic patients. 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 5 capsules of MTT or placebo the next day then 2 capsules daily for 26 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.

Part B is an open label phase II arm that aims at evaluating the role of MTT in sustained unresponsiveness. Patients who are on maintenance peanut oral immunotherapy (OIT) for a year will be enrolled. They will undergo an open label oral food challenge (OFC) to determine their threshold tolerated dose, after which they will start a week of antibiotics (Vancomycin and Neomycin). Patients will receive their 4 oral capsules of MTT under medical supervision, take another 4 capsules the next day then will start 2 capsules per day for a total of 12 weeks of MTT therapy , all while continuing maintenance peanut OIT. At the end of this course, patients will undergo another open label OFC to evaluate for any change in their tolerated dose . Subjects will then stop OIT and MTT for 12 weeks and will come back for a third OFC to evaluate for any change in their tolerated dose. An exit visit will occur 6 months post end of treatment.

Gut microbiota will be analyzed serially using state-of-the-art 16SRNA sequencing at baseline, post antibiotics (and prior to MTT initiation), then at 4, 8, 12, 16, 20 and 24 weeks post MTT initiation. Immunological biomarkers and mechanistic studies will be performed on blood taken at baseline, second and third OFC and exit visit. Adverse events will be monitored carefully throughout the study.

The study will enroll 24 peanut allergic patients aged 12-17 who meet the eligibility criteria in Part A and 13 subjects aged 12-17 years who meet eligibility criteria in Part B.

Inclusion criteria

Male and female young adults aged 12-17 years, who meet all the following inclusion criteria, will be enrolled in the study.

• 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 (Part A only).
• Has a positive SPT to peanut (≥3mm) and/or a positive peanut-specific IgE >0.35kU/L (Part A only).
• For asthmatic patients, has a Spirometry or Peak Flow with Measurement of FEV1>=80% of predicted
• Has a negative urine hCG test if a female participant.
• 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.
• Able to swallow 2 empty capsules size 00.
• Able to give informed assent and guardian willing to give informed consent.
• Willing and able to participate in the study requirements, including study visits, food challenges, serial stool collection
• Willing to undergo telephone or email follow-up to assess for safety and adverse events.
• Subject has been on maintenance peanut oral immunotherapy for at least a year (part B only).

Exclusion criteria

Subjects who fall into any of the following exclusion criteria at the time of screening are not eligible for enrollment into the study.

• Patients with a history of severe anaphylaxis to any food (hypotension requiring vasopressor support, hypoxia requiring mechanical ventilation, or neurological compromise)
• For Part A, patients with current diagnosis of an IgE mediated reactions to food (excluding allergic reactions to peanut, tree nuts, egg and milk, provided that MTT does not contain traces of these food estimated to be above the LOAEL in 5 capsules combined, and excluding oral allergy syndrome, and excluding other foods that the MTT donor avoided)
• For Part B, patients with current diagnosis of an IgE mediated reactions to food (excluding allergic reactions to peanut, tree nuts, egg and milk, provided that MTT does not contain traces of tree nuts, egg and milk estimated to be above the LOAEL in 4 capsules, and excluding oral allergy syndrome, excluding the food that the patient is undergoing immunotherapy to, and excluding other foods that the MTT donor avoided).
• 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.
• Recurrent or chronic infections necessitating frequent systemic (including oral) antibiotic administration.
• Patients on chronic systemic immunosuppressive therapies.
• Patients who are diagnosed with active, chronic urticaria.
• Patients who have received peanut oral immunotherapy within the past 6 months (Part A only).
• 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.
• Women who are pregnant or breast feeding or planning to get pregnant during the time of the study.
• Sexually active female patients who refuse to use contraception from enrollment through the third DBPCFC study visit
• 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.
• Patient with current rheumatologic conditions. Exceptions can be made per PI discretion if illness is not expected to affect allergies or treatment.
• Patients with neutropenia <1000 cells/uL
• Patients participating or planning to participate in the next 6 months in interventional research trials. Exceptions can be made per PI discretion.
• Patients who have received systemic corticosteroids therapy for 1 week or more over the past 60 days.
• Patient with an allergy to Vancomycin or Neomycin or any component to the capsules.