Oral Bacterial Extract for the Prevention of Wheezing Lower Respiratory Tract Illness (ORBEX)

Randomized, Placebo-controlled, Multicenter Study to Assess the Efficacy, Safety and Tolerability of ORal Bacterial EXtract for the Prevention of Wheezing Lower Respiratory Tract Illness (ORBEX)

The primary objective of this study is to evaluate if Broncho-Vaxom® given to high risk infants for 10 days, monthly, for two consecutive years can increase time to occurrence of the first episode of wheezing lower respiratory tract illness (WLRI) during a three year observation period off therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Asthma; Wheezing
• Intervention / Treatment: Drug: Broncho-Vaxom (BV); Other: Placebo

Detailed Description

This is a five year parallel arm, double-blind, placebo-controlled trial for the prevention of WLRI into the third to seventh year of life (30 to 78 mo inclusive) in young children (6-18 months old) at increased risk for asthma. The trial will be divided into 2 periods. During the initial treatment period (first and second years in the study) participants will receive Broncho- Vaxom® (3.5 mg) or placebo for ten days each month for two consecutive years. This period will allow the observation of key secondary outcomes while participants are receiving therapy. The second period (third through fifth years in the study) will be a three year observation of the time to occurrence of the first WLRI episode (primary outcome) while off study drug along with the secondary outcomes noted above. During both the treatment and observation periods, participants will be managed by study physicians using a rescue algorithm applied in the PEAK trial commensurate with the NAEPP Expert Panel Report (EPR) III guidelines.

• Study Type: Interventional
• Enrollment (Actual): 822
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Oakland, California, United States, 94609
      • University of California San Francisco, Benioff Children's Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Children's National Health System
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital, Harvard University
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital & Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-4108
      • University Of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 1 year (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adequate completion of informed consent process with written documentation. The participant's legally acceptable representative must have provided the appropriate written informed consent. Assent forms will not be used due to the age of the participant population; however, for procedures later in the study when participants are older, age appropriate assent will be obtained, if required by local Institutional Review Board (IRB).
• Age: 6-18 months of age inclusive at randomization which means 5 to 17 months of age inclusive on entry into the one month run-in period. At least half of all enrolled children will be between 6 and 12 months of age at randomization.
• Participants will meet at least one of the following criteria, which have been associated with an increased risk of wheezing respiratory illnesses and asthma: a) Parental history of asthma -or- b) Physician-diagnosed atopic dermatitis in the participant - or- c) Physician-diagnosed asthma in a blood sibling aged 4 years or more.
• Participants may be either male or female.
• Participants will have at least one parent/guardian who can communicate with the study staff to allow assessment of study outcomes. All study materials used by parent/guardian will be made available in English and in Spanish.

The child's parent/guardian must have a working direct contact telephone.

Exclusion Criteria:

• Participants may not have had more than two prior WLRI episodes.
• Participants may not have had any SWLRI episodes.
• Participants may not have a physician's diagnosis of asthma.
• Participants may not have a systemic illness (other than allergy) including (but not limited to) recurrent seizures, chronic gastroesophageal reflux (GER) requiring medical treatment, major congenital anomalies, physical and intellectual delay, cerebral palsy, chest surgery, tuberculosis or other chronic infections, primary or secondary immunodeficiency, gastrointestinal malformation or disease or cardiac disorder (except a hemodynamically insignificant atrial septal defect (ASD), ventricular septal defect (VSD) or benign heart murmur).
• Participants may not have been born earlier than 36 weeks of gestation.
• Participants may not have received oxygen for more than 5 days in the neonatal period, or received mechanical ventilation with the exclusion of ventilation during anesthesia for a minor surgical procedure.
• Participants may not have significant neurodevelopmental delay.
• Participants may not be below the 3rd percentile for weight.
• Participants may not have any other chronic lung disease; e.g. chronic lung disease of prematurity (CLDP) or cystic fibrosis.
• Participants may not have a history of any life-threatening respiratory illness that required intubation and mechanical ventilation.
• The participant's family may not be expected to relocate out of study area within 3 years of the initiation of the study.
• Participants may not have received inhaled or systemic corticosteroids for respiratory related illness ever, or for other conditions in the month prior to randomization.
• Participants may not have ever received immunotherapy.
• Participants may not have ever received i.v. gammaglobulins or systemic immunosuppressants.
• Participants may not have received probiotics (Lactobacilli and Bifidobacteria) in medicinal form; (i.e. not including food), regularly for more than 4 months in the 6 to <12 mo age group or 6 months in the 12 to 18 month group prior to enrollment.
• Participant has known sensitivity to any of the study products and any of the ingredients to be administered.
• Participant has previously been randomized in this study. Participants who failed run-in and were not randomized may have study participation terminated and then be re-enrolled for a second run-in period.
• Participant is currently enrolled in or has completed any other investigational device or drug study <30 days prior to screening, or is receiving other investigational agent(s).
• Participant has a significant medical condition(s), anticipated need for major surgery during the study, or any other kind of disorder that may be associated with increased risk to the participant, or may interfere with study assessments, outcomes, or the ability to provide written informed consent or comply with study procedures, in the Investigator's opinion.
• The one month run-in period will be used to evaluate adherence to study drug administration and electronic communication. At randomization the participant must continue to meet enrolment criteria and also have demonstrated 80% adherence to the placebo during treatment period; i.e. 8 out of 10 days and a75% response rate to weekly mobile phone text queries; i.e. 3 out of 4 weekly text queries.
• Ongoing infection (of any organ system) at the time of randomization. This includes infections that are being adequately treated.
• Unable or unlikely to complete study assessments or the study intervention poses undue risk to patient in the opinion of the Investigator.
• Families will speak English and/or Spanish.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Broncho-Vaxom (BV); One capsule of Broncho-Vaxom for children contains: 3.5 mg of lyophilized bacterial lysates of Haemophilus influenzae, Streptococcus (pneumonia, pyogenes and sanguinis (viridans)), Klebsiella (pneumoniae and ozaenae), Staphylococcus aureus and Moraxella catarrhalis. The content of the capsule will be mixed with a palatable liquid such as fruit juice.	Drug: Broncho-Vaxom (BV); Active Ingredient: Lyophilised bacterial extract; Chemical Name: OM-85 BV; Strength: 3.5 mg; Excipients: bacterial extract, propyl gallate, sodium glutamate, mannitol, pregelatinised starch, magnesium stearate; Appearance: Blue and white capsule; Dosage Form: 3.5 mg capsule; Manufacturer: OM Pharma, Switzerland (OM stands for Omnia Medicamenta) Storage: Store in the original package; Other Names: OM-85 BV VEGETAL; Broncho-Vaxom concentrate (bacterial lysate)
Placebo Comparator: Placebo; A placebo capsule will be used that will be indistinguishable from the active study drug.	Other: Placebo; A placebo capsule will be used that will be indistinguishable from the active study drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time to the occurrence of the first WLRI episode in the observation period while not receiving study drug	The time to the occurrence of the first WLRI episode in the observation period while not receiving study drug	ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time to first WLRI during the two treatment years while receiving study drug	The time to first WLRI during the two treatment years while receiving study drug	ages 6 to 18 months at start of therapy; ages 30 to 42 months at completion
The annualized rate of WLRI episodes during the two years while receiving study drug	The annualized rate of WLRI episodes during the two years while receiving study drug	ages 6 to 18 months at start of therapy; ages 30 to 42 months at completion
The annualized rate of WLRI episodes during the observation period while not receiving study drug	The annualized rate of WLRI episodes during the observation period while not receiving study drug	ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion
The annualized rate of severe wheezing respiratory tract illness (SWLRI) episodes during the two treatment years while receiving study drug.	SWLRI episodes are defined as cough and wheezing > 24 hours AND any one of the following: Use of more than 6 albuterol treatments in ≤48 hours.; Unscheduled care visit for acute wheezing in doctor's office, urgent care or emergency department -or- hospitalization for wheezing.; Use of systemic corticosteroid prescribed by a licensed medical provider for a wheezing illness with or without a clinical visit.; The annualized rate of SWLRI episodes during the two years while receiving study drug.	ages 6 to 18 months at start of therapy; ages 30 to 42 months at completion
The annualized rate of severe wheezing respiratory tract illness (SWLRI) episodes during the observation period while not receiving study drug.	The annualized rate of severe wheezing respiratory tract illness (SWLRI) episodes during the observation period while not receiving study drug.	ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion
Asthma at the end of the observation period	Asthma at the end of the observation period defined by any of the following three elements: (a) a health care provider diagnosis of asthma with reports of: at least one episode of wheezing or asthma in the previous year or asthma controllers prescribed for at least 6 months during the previous year; or (b) >3 episodes of wheezing during the previous year 38 ("frequent wheezers"); or (c) any wheezing during the third observation year in children who wheezed during the first three years of life ("persistent wheezers").	ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion
Safety and tolerability of Broncho-Vaxom® while receiving study drug during the two year treatment period.	Safety and tolerability of Broncho-Vaxom® while receiving study drug during the two year treatment period	ages 6 to 18 months at start of therapy; ages 30 to 42 months at completion
Safety and tolerability of Broncho-Vaxom® while receiving study drug during the observation period.	Safety and tolerability of Broncho-Vaxom® while receiving study drug during the observation period, after study drug has been stopped.	ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of episode free days (EFD) annualized for each year of study.	shortness of breath, cough, chest retraction or tightness; 2) No unscheduled medical visits for respiratory symptoms AND 3) No use of any asthma medications, including albuterol before exercise.	Treatment (2 yr) and observation periods
Time to first systemic corticosteroid course	Time to first systemic corticosteroid course	Treatment (2 yr) and observation periods
Number of systemic corticosteroid courses	Number of systemic corticosteroid courses	Treatment (2 yr) and observation periods
Cumulative systemic corticosteroid courses	Cumulative systemic corticosteroid courses	Treatment (2 yr) and observation periods
Cumulative systemic corticosteroid dose	Cumulative systemic corticosteroid dose	Treatment (2 yr) and observation periods
Cumulative time receiving controller inhaled corticosteroid (ICS)	Cumulative time receiving controller inhaled corticosteroid (ICS)	Treatment (2 yr) and observation periods
Cumulative does of controller ICS	Cumulative does of controller ICS	Treatment (2 yr) and observation periods
Cumulative time of receiving any controller medication (ICS, systemic steroid, or montelukast)	Cumulative time of receiving any controller medication (ICS, systemic steroid, or montelukast)	Treatment (2 yr) and observation periods
Days with albuterol use	Days with albuterol use	Treatment (2 yr) and observation periods
Urgent care/Emergency Department (ED)/Office visits/hospitalizations for respiratory illness analyzed separately and combined variable	Urgent care/ED/Office visits/hospitalizations for respiratory illness analyzed separately and combined variable	Treatment (2 yr) and observation periods
Change in height and weight from baseline	Change in height and weight from baseline	Treatment (2 yr) and observation periods

Collaborators and Investigators

• Sponsor: University of Arizona
• Investigators: Study Director: Wayne J Morgan, MD, University of Arizona; Study Director: Dave T Mauger, PhD, Penn State University, Data Coordinating Center; Principal Investigator: Fernando D Martinez, MD, University of Arizona

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2017
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: May 19, 2014
• First Submitted That Met QC Criteria: May 22, 2014
• First Posted (Estimate): May 28, 2014

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Asthma; Wheezing; Atopy; Lower respiratory tract illness
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Respiratory Sounds; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Broncho-Vaxom
• Other Study ID Numbers: ORBEX-BV2014/06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO