Impact of Bi-26 Supplementation on Weight Gain in Underweight Infants

Study Overview
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Brief Summary
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The burden of disease experienced by underweight children is significant, particularly in low- and middle-income countries. Gut dysbiosis, an imbalance in microbial composition, is thought to play a role in nutrient malabsorption leading to underweight infants and failure to thrive. Bifidobacterium longum subspecies infantis (B. infantis) is a commensal bacterial strain important in the breakdown of human milk oligosaccharides (HMOs). A decrease in abundance or absence of B. infantis could lead to inadequate HMO processing, elevating intestinal pH and increasing the risk of pathogen overgrowth. Bi-26 is a B. infantis probiotic strain that is being evaluated in this study for its impact on weight gain and other health outcomes in underweight infants.

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Bi-26 (Strain of Bifidobacterium Longum, B. Infantis) Supplementation Versus Placebo on Weight Gain in Underweight Infants

Conditions
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Underweight, Paediatrics

Intervention / Treatment
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* Dietary Supplement: B. infantis Bi-26
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be between 30 days and 120 days of age (inclusive), at the time of enrollment (study Day 1) Hospitalized for acute non-surgical illness Completed acute stabilization phase of treatment, including fluid rehydration and antibiotic course, prior to enrollment (study Day 1) WAZ at enrollment (study Day 1) is less than negative 2 (<-2) Any sex Participant's parent(s)/legal guardian is capable of giving informed consent which includes agreement to comply with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol Participant's parent(s)/legal guardian agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to relocate from the study area for the duration of the study Participant's parent(s)/legal guardian has easy access to reliable refrigeration (for storage of investigational product) Participant receives some feedings from breastmilk and mother intends to continue breastfeeding. Exclusion Criteria: Congenital condition (suspected or confirmed) that the investigator considers likely to interfere with feeding or with normal growth and development Infant has not been discharged from hospital since birth or has not been at home for at least one week since birth Infant hospitalized with septic shock during current hospitalization Infant required mechanical ventilation during current hospitalization Infant with acute kidney injury on hospital admission Infant with severe jaundice and suspected kernicterus Infant receiving treatment for suspected or confirmed tuberculosis, or suspected or confirmed human immunodeficiency virus (HIV) infection Ongoing infant antibiotic (e.g. as prophylaxis in sickle cell disease) and/or probiotic usage Ongoing maternal antibiotic and/or probiotic usage for breast-feeding infants Inability of participant's parent(s)/legal guardian to comply with protocol requirements, as per investigator assessment.

Ages Eligible for Study
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Minimum Age: 30 Days
Maximum Age: 120 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bi-26 supplementation<br>Bi-26 administered daily. | Dietary Supplement: B. infantis Bi-26<br>* A once-daily oral dose of Bi-26 will be provided to infants for 28 days.<br>|
| Placebo Comparator: Placebo<br>Maltodextrin: Placebo administered daily | Dietary Supplement: Placebo<br>* A once-daily oral dose of placebo maltodextrin will be provided to infants for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Weight-for-age Z score (WAZ) to Day 56 visit in Bi-26 group | Weight for age Z score will be calculated using the World Health Organization standard reference tables. The z score is a measure of the number of standard deviations that an observation is above or below the mean. A positive z score indicates that the observation is above the mean, a negative z score that the observation is below the mean. | Baseline (Day 1) and up to Day 56 visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in weight to Day 56 visit in Bi-26 group |  | Baseline (Day 1) and up to Day 56 vist | 
| Change from Baseline in WAZ over time through Day 90 visit in Bi-26 group by duration of dosing |  | Baseline (Day 1) and up to Day 90 visit | 
| Percentage of infants with a ≥ 0.3, ≥ 0.4, and ≥ 0.5 change in WAZ from Baseline to Day 56 |  | Baseline (Day 1) and up to Day 56 visit | 
| Percentage of infants who will achieve a WAZ > -2 at Day 56 |  | Baseline (Day 1) and up to Day 56 visit | 
| Number of re-hospitalizations for acute non-surgical illness |  | Baseline (Day 1) and up to Day 56 visit | 
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) |  | Baseline (Day 1) through Day 90 visit | 
| Number of participants with presence of B. infantis in stool |  | At randomization (Day 1), and at Days 28, 56 and Day 90 visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Weight-for-age Z score, Underweight infants, Bifidobacterium longum, B. infantis, Bi-26 supplementation