Allergic Disease Onset Prevention Study

Study Overview
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Brief Summary
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This is a Phase 1b/2, randomized, double-blind, multi-center study to evaluate the safety, tolerability, and preliminary clinical efficacy of STMC-103H in neonates and infants at risk for developing allergic disease (Type 1 hypersensitivity). Subjects will be enrolled in a three-part sequential approach. Participants in the safety-run portion of the study (Part A1: 1 year to <6 years of age and A2: 1 month to <12 months of age) will receive 28 days of treatment with STMC-103H or placebo, followed by 28 days of follow-up. A Data and Safety Monitoring Committee (DSMC) will review safety data after all patients in each part complete 28 days of therapy prior to enrolling the next part. After A2, Part B will enroll 224 patients for 336 days of treatment with STMC-103H or placebo, followed by 336 days of follow-up. Stool, blood, and optional samples will be collected in Parts A2 and part B. Primary safety endpoints are frequency, type and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), as well as findings on physical exams, vitals, and safety laboratories. The primary efficacy endpoint is incidence of physician-diagnosed atopic dermatitis at day 336.

Official Title
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A Phase 1b/2, Randomized, Double-blind, Placebo-controlled, Multi-center Study of STMC-103H in Neonates and Infants at Risk for Developing Allergic Disease

Conditions
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Atopic Dermatitis, Type 1 Hypersensitivity

Intervention / Treatment
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* Biological: STMC-103H
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All Parts (A1, A2, B) Subject's parent(s)/legal representative(s) providing consent must be 18 years or older Biological mother and/or biological father and/or full sibling(s), have a history of asthma, atopic dermatitis, food allergy, or allergic rhinitis as determined by the screening questionnaire Subject's parent(s)/legal representative(s) (if appropriate according to local laws) is/are willing and able to give informed consent for participation in the study Subject's parent(s)/legal representative(s) (if appropriate according to local laws) is/are willing and able, in the PI's opinion, to comply with all study requirements Part A1 Only Inclusion criteria 1-4 for all parts plus: 5 (A1). Subject is between 1 year and < 6 years old at the time of enrollment Part A2 Only Inclusion criteria 1-4 for all parts plus: 5 (A2). Subject is between 28 days and < 12 months of life at the time of enrollment 6 (A2). Subject's parent(s)/legal representative(s) do not plan to give probiotics (including infant formula that contain probiotics) to the subject during the trial Part B Only Inclusion criteria 1-4 for all parts plus: 5 (B). Subject is ≤ 14 days of life at the time of enrollment. Sites should make every effort to enroll newborns as soon as possible after birth. 6 (B). Subject has a birthweight ≥ 2.5 kg and ≤ 4.5 kg 7 (B). Subject's parent(s)/legal representative(s) do not plan to give probiotics (including infant formula that contain probiotics) to the subject from the time of birth to the end of the trial. Exclusion Criteria: All Parts (A1, A2, B) Subject's twin (or higher order multiple) is enrolled in STMC-103H-102 Subject has any congenital abnormalities or condition, significant disease, illness, physical exam finding, or disorder that, in the opinion of the PI, may put the subject at safety risk or is likely to hinder feeding or affect metabolism that may influence the results of the study. (Neonatal hyperbilirubinemia (jaundice), including jaundice that requires phototherapy, should not be considered exclusionary). Subject is acutely ill or on systemic antibiotics at the time of enrollment Subject is participating in another interventional clinical study involving investigational medication, formula, probiotic, or prebiotic use within 30 days (or five half-lives, whichever is longer) of this study Subject has evidence of immune deficiency/immune compromise in the judgment of the investigator Part B Only Exclusion Criteria 1-5 for all parts plus: 6 (B). Subject was born at < 35 weeks' gestation 7 (B). Biological maternal medical condition during the pregnancy that, in the opinion of the PI, may put the subject at risk because of participation in the study. (Maternal antibiotics during the time of delivery should not be considered exclusionary.)

Ages Eligible for Study
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Minimum Age: 0 Days
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be enrolled in a three-part sequential approach (Parts A1, A2, and B). Part A will enroll at risk participants of 1 year to less than 6 years of age; after safety review, Part A2 will enroll at risk participants of 1 month to less than 12 months of age; and after safety review, Part B will enroll at -risk participants between 0 and 14 days of life.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STMC-103H Part A1<br>Once daily dosing with one capsule of STMC-103H mixed with milk, formula, or a milk product for 28 days | Biological: STMC-103H<br>* STMC-103H is a live biotherapeutic product (LBP) containing a consortium of intestinal bacteria<br>|
| Placebo Comparator: Placebo Part A1<br>Once daily dosing with one capsule of placebo mixed with milk, formula, or a milk product for 28 days | Biological: Placebo<br>* Powder containing excipients found in STMC-103H: magnesium stearate, mannitol and silicon dioxide.<br>|
| Experimental: STMC-102H Part A2<br>Once daily dosing with one capsule of STMC-103H mixed with milk, formula, or a milk product for 28 days | Biological: STMC-103H<br>* STMC-103H is a live biotherapeutic product (LBP) containing a consortium of intestinal bacteria<br>|
| Placebo Comparator: Placebo Part A2<br>Once daily dosing with one capsule of placebo mixed with milk, formula or a milk product for 28 days | Biological: Placebo<br>* Powder containing excipients found in STMC-103H: magnesium stearate, mannitol and silicon dioxide.<br>|
| Experimental: STMC-103H Part B<br>Once daily dosing with one capsule of STMC-103H mixed with breastmilk, formula or a milk product for 336 days | Biological: STMC-103H<br>* STMC-103H is a live biotherapeutic product (LBP) containing a consortium of intestinal bacteria<br>|
| Placebo Comparator: Placebo Part B<br>Once daily dosing with one capsule of placebo mixed with breastmilk, formula or a milk product for 336 days | Biological: Placebo<br>* Powder containing excipients found in STMC-103H: magnesium stearate, mannitol and silicon dioxide.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A1 and A2: Assess safety and tolerability of STMC-103H in children and infants at risk for development of allergic disease by assessing adverse events (AE), serious adverse events (SAE), and AEs of special interest | Frequency, type, and severity of AEs and SAEs, including AEs of special interest (AESI) as in Appendix 9 (Adverse Events of Special Interest) and Appendix 10 (Adverse Event Grading Scale) | Through 56 days of study | 
| Part B: Assess the safety, tolerability of STMC-103H in neonate and infants subjects at risk for development of atopic disease by monitoring AEs, SAEs, AESI, physical exam findings, and clinical safety laboratories. | Frequency, type and severity of AEs, SAEs, and AESIs as in Appendix 9 (Adverse Events of Special Interest) and Appendix 10 (Adverse Event Grading Scale), as well as clinically significant findings on physical examinations including growth (length, weight, height and head circumference) and vital signs (RR, HR, and temperature); clinical safety laboratories including complete blood count with manual differential and blood chemistry | Through 672 days of study | 
| Part B: Primary Efficacy Endpoint: Incidence of physician-diagnosed atopic dermatitis at 336 days | Incidence of physician-diagnosed atopic dermatitis at 336 days in STMC-103H-treated subjects compared to placebo | Day 336 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B Secondary Efficacy Endpoint - physician-diagnosed atopic dermatitis | Incidence of physician-diagnosed atopic dermatitis | At days 168 and 672 | 
| Part B - Secondary Efficacy Endpoint - atopic disease assessments | Proportion of subjects who develop any atopic disease (atopic dermatitis, food allergy, allergic rhinitis/conjunctivitis, asthma) | At days 168, 336 and 672 | 
| Part B Secondary Efficacy Endpoint - incidence of sensitization to food and aeroallergen | Incidence of sensitization to food and aeroallergen as measured by specific serum IgE levels | At days 168, 336, and 672 | 
| Part B Secondary Efficacy Endpoint - incidence of food allergy, allergic rhinitis/conjunctivitis, urticaria, and wheezing illness/asthma | Incidence of physician-diagnosed food allergy, allergic rhinitis/conjunctivitis, urticaria and wheezing illnesses/asthma using physician assessment, Allergic Disease Assessment and Diagnosis questionnaire, and Allergic Disease Diagnostic Criteria & Severity Evaluation | At days 168, 336, and 672 | 
| Part B Secondary Efficacy Endpoint - Time to atopic dermatitis diagnosis | Time to atopic dermatitis diagnosis by physician assessment | Through 672 days of study | 
| Part B Secondary Efficacy Endpoint - Time to first wheezing episode | Time to first wheezing episode by physician assessment | Through 672 days of study | 
| Part B Secondary Efficacy Endpoint - severity of atopic dermatitis by Investigator Global Assessment x Body Surface Area (IGAxBSA) assessment | Severity of atopic dermatitis by IGAxBSA assessment | At days 168, 336 and 672 | 
| Part B Secondary Efficacy Endpoint - severity of atopic dermatitis by Severity Scoring Of Atopic Dermatitis (SCORAD) assessment | Severity of atopic dermatitis by SCORAD assessment | At days 168, 336 and 672 | 
| Part B Secondary Efficacy Endpoint - Severity of Wheezing Illness/Asthma | Severity of wheezing illness/asthma by Wheezing Severity Assessment | At days 68, 336, and 672 days | 
| Part B Secondary Efficacy Endpoint - use of concomitant medications for allergic symptoms or diagnosis | Concomitant medications prescribed/used for allergic symptoms or diagnosis and use of rescue medications for atopic dermatitis and wheezing/asthma | Through 672 days of study | 
| Part B Secondary Efficacy Endpoint - Total Serum IgE | Total serum IgE levels | At days 168, 336, and 672 | 
| Part B Secondary Efficacy Endpoint - Peripheral Eosinophil Counts | Peripheral eosinophil counts by automated differential | At day 336 |