Allergic Disease Onset Prevention Study (adored)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Atopic Dermatitis; Type 1 Hypersensitivity
• Intervention / Treatment: Biological: STMC-103H; Biological: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 264
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Elizabeth C Chesnut; Phone Number: 4048030358; Email: echesnut@sioltatherapeutics.com
• Study Contact Backup: Name: Richard Shames, MD; Phone Number: 6505750798; Email: rshames@sioltatherapeutics.com

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • The Children's Hospital at Westmead
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Queensland Children's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • The Women's and Children's Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Children's Hospital
    • Parkville, Victoria, Australia, 3052
      • Murdoch Children's Research Institute
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Centro de Neumologia Pediatrica
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Health Sciences
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Research Institute
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Health
    • San Diego, California, United States, 92123
      • Rady Children's Hospital - San Diego
    • San Francisco, California, United States, 94158
      • UCSF Benioff Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Children's Health at University of Indiana
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • University of Michigan Health
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Healthcare
    • New York, New York, United States, 10016
      • NYU Langone Fink Children's
    • New York, New York, United States, 10029
      • Mt. Sinai Jaffe Allergy Institute
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati CHildren's Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research
    • Summerville, South Carolina, United States, 29486
      • Coastal Pediatrics Research
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Medical School at UT Austin
    • Dallas, Texas, United States, 75235
      • UT Southwestern/Children's Health
  • Washington
    • Seattle, Washington, United States, 98115
      • Seattle Allergy and Asthma Research Institute
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Univ. of Wisconsin-Madison/Jackson Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 2 weeks (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• All Parts (A1, A2, B)

  1. Subject's parent(s)/legal representative(s) providing consent must be 18 years or older
  2. 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
  3. 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
  4. 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)

  1. Subject's twin (or higher order multiple) is enrolled in STMC-103H-102
  2. 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).
  3. Subject is acutely ill or on systemic antibiotics at the time of enrollment
  4. 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
  5. 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.)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B Key Exploratory Endpoint - Mean fecal concentration of 12,13-diHOME	Mean fecal concentration of 12,13-diHOME measured in stool sample in STMC-103H arm as compared to placebo arm	At day 336

Collaborators and Investigators

• Sponsor: Siolta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: August 11, 2021
• First Posted (Actual): August 12, 2021

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity; Dermatitis; Hypersensitivity, Immediate
• Other Study ID Numbers: STMC-103H-102

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