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

• ClinicalTrials.gov Identifier: NCT02148796
• Recruitment Status: Active, not recruiting
• First Posted: May 28, 2014
• Last Update Posted: May 9, 2023
• Sponsor: University of Arizona
• Information provided by (Responsible Party): University of Arizona

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Asthma; Wheezing	Drug: Broncho-Vaxom (BV); Other: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 822 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: 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)
• Actual Study Start Date: January 3, 2017
• Estimated Primary Completion Date: December 31, 2025
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. The time to the occurrence of the first WLRI episode in the observation period while not receiving study drug [ Time Frame: ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion ]
   The time to the occurrence of the first WLRI episode in the observation period while not receiving study drug

Secondary Outcome Measures :

1. The time to first WLRI during the two treatment years while receiving study drug [ Time Frame: ages 6 to 18 months at start of therapy; ages 30 to 42 months at completion ]
   The time to first WLRI during the two treatment years while receiving study drug
2. The annualized rate of WLRI episodes during the two years while receiving study drug [ Time Frame: 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
3. The annualized rate of WLRI episodes during the observation period while not receiving study drug [ Time Frame: ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion ]
   The annualized rate of WLRI episodes during the observation period while not receiving study drug
4. The annualized rate of severe wheezing respiratory tract illness (SWLRI) episodes during the two treatment years while receiving study drug. [ Time Frame: ages 6 to 18 months at start of therapy; ages 30 to 42 months at completion ]

   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.
5. The annualized rate of severe wheezing respiratory tract illness (SWLRI) episodes during the observation period while not receiving study drug. [ Time Frame: 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 observation period while not receiving study drug.
6. Asthma at the end of the observation period [ Time Frame: 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 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").

7. Safety and tolerability of Broncho-Vaxom® while receiving study drug during the two year treatment period. [ Time Frame: 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 two year treatment period
8. Safety and tolerability of Broncho-Vaxom® while receiving study drug during the observation period. [ Time Frame: 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 observation period, after study drug has been stopped.

Other Outcome Measures:

1. The proportion of episode free days (EFD) annualized for each year of study. [ Time Frame: Treatment (2 yr) and observation periods ]
   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.
2. Time to first systemic corticosteroid course [ Time Frame: Treatment (2 yr) and observation periods ]
   Time to first systemic corticosteroid course
3. Number of systemic corticosteroid courses [ Time Frame: Treatment (2 yr) and observation periods ]
   Number of systemic corticosteroid courses
4. Cumulative systemic corticosteroid courses [ Time Frame: Treatment (2 yr) and observation periods ]
   Cumulative systemic corticosteroid courses
5. Cumulative systemic corticosteroid dose [ Time Frame: Treatment (2 yr) and observation periods ]
   Cumulative systemic corticosteroid dose
6. Cumulative time receiving controller inhaled corticosteroid (ICS) [ Time Frame: Treatment (2 yr) and observation periods ]
   Cumulative time receiving controller inhaled corticosteroid (ICS)
7. Cumulative does of controller ICS [ Time Frame: Treatment (2 yr) and observation periods ]
   Cumulative does of controller ICS
8. Cumulative time of receiving any controller medication (ICS, systemic steroid, or montelukast) [ Time Frame: Treatment (2 yr) and observation periods ]
   Cumulative time of receiving any controller medication (ICS, systemic steroid, or montelukast)
9. Days with albuterol use [ Time Frame: Treatment (2 yr) and observation periods ]
   Days with albuterol use
10. Urgent care/Emergency Department (ED)/Office visits/hospitalizations for respiratory illness analyzed separately and combined variable [ Time Frame: Treatment (2 yr) and observation periods ]
    Urgent care/ED/Office visits/hospitalizations for respiratory illness analyzed separately and combined variable
11. Change in height and weight from baseline [ Time Frame: Treatment (2 yr) and observation periods ]
    Change in height and weight from baseline

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 18 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Phoenix Children's Hospital

Phoenix, Arizona, United States, 85016

University of Arizona

Tucson, Arizona, United States, 85724

United States, California

University of California San Francisco, Benioff Children's Hospital

Oakland, California, United States, 94609

United States, District of Columbia

Children's National Health System

Washington, District of Columbia, United States, 20037

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Massachusetts

Boston Children's Hospital, Harvard University

Boston, Massachusetts, United States, 02115

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110

United States, New York

Columbia University

New York, New York, United States, 10032

United States, North Carolina

University of North Carolina

Chapel Hill, North Carolina, United States, 27514

United States, Ohio

Cincinnati Children's Hospital & Medical Center

Cincinnati, Ohio, United States, 45229

United States, Wisconsin

University of Wisconsin

Madison, Wisconsin, United States, 53792-4108

Sponsors and Collaborators

University of Arizona

Investigators

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

More Information

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• Responsible Party: University of Arizona
• ClinicalTrials.gov Identifier: NCT02148796
• Other Study ID Numbers: ORBEX-BV2014/06
• First Posted: May 28, 2014
• Last Update Posted: May 9, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by University of Arizona:

Wheezing; Lower respiratory tract illness; Asthma; Atopy

Additional relevant MeSH terms:

Respiratory Sounds; Signs and Symptoms, Respiratory; Broncho-Vaxom; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs