A Study of a Probiotic Food Supplement Containing B. Infantis (EVC001) in Healthy Breastfed Infants at Risk of Developing Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of B. infantis (EVC001) versus placebo supplementation, in healthy breastfed infants at risk of developing atopic dermatitis (AD), on cumulative incidence of physician-diagnosed AD during the first year of life.

Official Title
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A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled, Two-Arm, Parallel-Group, Nutritional Intervention Study to Examine the Clinical and Immunological Effects of a Probiotic Food Supplement Containing B. Infantis (EVC001) in Healthy Breastfed Infants at Risk of Developing Atopic Dermatitis

Conditions
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Healthy

Intervention / Treatment
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* Other: B. infantis
* Other: Lactose Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy term infant Has at least one first degree relative (that is biological parent or full sibling) with a history of atopic disease (that is mother-reported, physician-diagnosed Atopic Dermatitis (AD), allergic rhinitis, or asthma) Breastfeeding established (as determined by the principal Investigator [PI] or designee) at the time of study enrollment (Day 0), with maternal intent to maintain exclusive breastfeeding for greater than or equal to (>=)12 weeks Will participate in the study under supervision of his/her biological mother (Caregiver) who is: a) At least 18 years old b) The legal guardian of the infant c) Intending to cohabitate with the infant for the duration of the study d) Willing to follow all Caregiver responsibilities e) Fluent in Finnish, Swedish, or English The PI considers the Caregiver likely to adequately comply with the study protocol requirements based on demonstrated compliance with antenatal appointments and agreement to complete the intuitive, interactive, electronic diary (eDiary) utilizing personal smart device (example, tablet, cell phone) Exclusion Criteria: Preterm delivery (< 36 weeks [252 days] gestational age) Admission to the neonatal unit for issues other than establishment of normal feeding Evidence of a baseline illness/condition (example abnormal birth weight) or significant risk of developing an illness/condition (based on review of maternal/pregnancy information) that would, in the opinion of the Principal Investigator (PI) or designee, introduce a significant safety concern if the infant were enrolled in the study or otherwise preclude study participation Significant birth defect/complication that would, in the opinion of the PI or designee, create a safety concern or otherwise confound the study (example, abdominal wall defects, congenital heart disease) Severe widespread skin condition (example collodion) Has consumed greater than (>)100 milliliter (mL) of formula per day within the 48 hours prior to enrollment (Day 0) Twin or multiple births Atopic dermatitis (AD) diagnosed at Day 0 Has a history of confirmed coronavirus disease 2019 (COVID-19) within 30 days prior to any on-site visit Within 14 days prior to Visit 1, has been in close contact (exposure within 6 feet for a cumulative time of 15 minutes or more over a 24-hour period) with anyone who has a confirmed case of COVID-19 Is under a COVID-19 isolation/quarantine order Has had self-reported (for Caregiver) or parent-reported (for infant) symptoms of COVID-19 within 14 days prior to the screening visit, such as unexplained cough, shortness of breath/difficulty breathing, fatigue, body aches (headaches, muscle pain, stomachaches), conjunctivitis, loss of smell, loss of taste, poor appetite, nausea, vomiting, diarrhea, palpitations, or chest pain/tightness

Ages Eligible for Study
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Maximum Age: 14 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B. infantis<br>A once-daily feeding of activated B. infantis EVC001 (8.0 *10^9 colony forming units [CFU]) will be provided to infants for 12 weeks. | Other: B. infantis<br>* Bifidobacterium longum subspecies infantis strain EVC001, designated a Foods for Special Dietary Use (FSDU), will be provided to infants once daily for 12 weeks.<br>* Other names: Evivo;|
| Placebo Comparator: Placebo<br>A once-daily oral feeding of lactose placebo will be provided to infants for 12 weeks. | Other: Lactose Placebo<br>* Powdered infant formula grade lactose will be provided to infants once daily for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Atopic Dermatitis (AD) through Week 52 | Number of participants with atopic dermatitis (AD) through Week 52 will be reported. AD will be diagnosed if three of the following four criteria are met: 1) pruritus, 2) typical morphology and distribution (facial and extensor involvement), 3) chronic or chronically relapsing dermatitis, 4) personal or family history of atopic disease. | Up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Infants with Adverse Events Through Weeks 12, 52 and 104 | The percentage of infants with AEs, serious adverse events (SAEs), AEs leading to discontinuation, and AEs related to the gastrointestinal system will be determined at Weeks 12, 52 and 104. | Up to Weeks 12, 52 and 104 | 
| Number of Participants with Atopic Dermatitis (AD) Through Weeks 24 and 104 | Number of participants with AD through Week 24 and 104 will be reported. AD will be diagnosed if three of the following four criteria are met: 1) pruritus, 2) typical morphology and distribution (facial and extensor involvement), 3) chronic or chronically relapsing dermatitis, 4) personal or family history of atopic disease. | Up to Weeks 24 and 104 | 
| Time to Onset of AD Through Weeks 52 and 104 | Time to onset of AD through Weeks 52 and 104 will be reported. | Up to Weeks 52 and 104 | 
| Percentage of Infants with B. infantis Gut Colonization at Week 12 | Percentage of infants with B. infantis gut colonization at Week 12 will be reported. | Week 12 | 
| Atopic Dermatitis (AD) Severity Based on the Eczema Area and Severity Index (EASI) Score at Time of AD Onset and at Weeks 12, 52, and 104 | Atopic Dermatitis (AD) severity based on the EASI score at time of AD onset and at Weeks 12, 52, and 104 will be reported. Physician rates severity of four parameters: erythema, infiltration, excoriation and lichenification on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Physician determines how much area is affected on a scale of 0 (none) to 6 (90 to 100%). A body region score is determined by multiplying the sum of the severity scores by the affected area score by a constant corresponding to the relative body surface area for that body region (20%, 30%, 20%, and 30%, respectively). The 4 body region scores are summed to yield the EASI score which ranges from 0 to 72, with a higher score indicating more severe AD. The AD onset in the study's population can be diagnosed throughout the study at either scheduled or unscheduled visits starting as early as 1 month of age. | At the time of AD onset (up to Week 104), Weeks 12, 52, and 104 | 
| AD Severity Based on the Patient-Oriented Eczema Measure (POEM) Score at Time of AD Onset and at Weeks 12, 52, and 104 | The POEM is a simple, valid, easily interpreted, and reproducible tool for assessing AD and monitoring aspects of the disease that are important to participants with AD. Study Personnel will interview Caregivers at time of AD diagnosis and (only for participants with AD) at Weeks 12, 52, and 104 to rate seven symptoms (itchy skin, sleep disturbance, bleeding skin, skin weeping/oozing, skin flaking, skin cracking, skin dryness/roughness) using a 5-point scale of frequency of occurrence during the previous week (no days, 1-2 days, 3-4 days, 5-6 days, every day). The total score is the sum of the 7 items which is ranged from 0 to 28; a high score is indicative of more severe AD. The AD onset in the study's population can be diagnosed throughout the study at either scheduled or unscheduled visits starting as early as 1 month of age. | At the time of AD onset (up to Week 104), Weeks 12, 52, and 104 |