Prevention of OM-85 on Bronchiectasis Exacerbation

To Investigate the PRevention of OM-85 on Bronchiectasis Exacerbation (iPROBE): a Multicenter, Randomised, Double-dummy, Placebo-controlled Clinical Trial in Chinese Patients

Non-cystic fibrosis bronchiectasis is characterized by irreversible dilatation of the medium-sized bronchi as a result of airway injury due to recurrent or chronic inflammation and infection. Bronchiectasis airways are often colonized with bacterial species. Infections of the airways are thought to play an important role in bronchiectasis exacerbation. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing scientific interest. OM-85, consisting extracts of eight kinds of bacteria important in respiratory infections, has shown the benefit for significantly reducing the incidence of exacerbations of chronic obstructive pulmonary disease (COPD). The purpose of this study is to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE).

This study is designed as a prospective randomised double-blind placebo-controlled multi-centred trial.

Study Overview

• Status: Completed
• Conditions: Bronchiectasis With Acute Exacerbation
• Intervention / Treatment: Drug: OM-85 BV

Detailed Description

Bronchiectasis is still a common chronic respiratory disease. Non-cystic fibrosis bronchiectasis is characterized by irreversible dilatation of the medium-sized bronchi as a result of airway injury due to recurrent or chronic inflammation and infection. Clinical features of bronchiectasis include chronic production of sputum often mucopurulent or purulent in nature, persistent bacterial colonization, recurrent lower respiratory tract infections. Bronchiectasis airways are often colonized with bacterial species. Infections of the airways are thought to play an important role in bronchiectasis exacerbation. Progressive lung damage in bronchiectasis results from a 'vicious cycle' of recurrent bacterial infection and a deregulated inflammatory response. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing scientific interest. OM-85, consisting extracts of eight kinds of bacteria important in respiratory infections, has been known to support the respiratory tract resistance to the pathogens via activating pulmonary macrophages, increasing the ratio of CD4 to CD8 lymphocytes, and changing the level of a variety of cytokines in the lung. OM-85 has shown the benefit for significantly reducing the incidence of exacerbations of chronic obstructive pulmonary disease (COPD). Bronchiectasis exacerbations contribute substantially to rapid decline in lung function, reduced quality of life, and the medical costs. The purpose of this study is to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE).

This study is designed as a prospective randomised double-blind placebo-controlled multi-centred trial. A total of 244 patients with bronchiectasis, who have had at least one exacerbation of bronchiectasis in the previous year, will be included. The subjects will be randomly received two courses of 7mg of OM-85 or matching placebo to take one oral capsule per day for 10 days a month for 3 consecutive months at the beginning of the study, then 3 months later with the same schedule for 1 year.

We will investigate whether long-term therapy with an oral immunostimulant OM-85 can decrease exacerbations in patients with bronchiectasis over 1-year period. Besides, we will assess other outcomes including: the rate of event-based exacerbation, lung function parameters, the total scores on the St George's respiratory questionnaire and coughing, and inflammatory index. We hope that this study will provide novel information on the preventive effects of OM-85 treatment on bronchiectasis exacerbation and will address a knowledge gap for this poorly understood and under-studied disease.

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Shanghai, China
    • Shanghai Tongji University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the subject. The Informed Consent form will be signed.
• Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule or medication intake according to the judgment of the investigator.
• Subject with both genders is adult patients (>18 years) diagnosed with bronchiectasis by high-resolution computed tomography (HRCT) of chest within 3 years of study inclusion having had at least 1 acute exacerbation in the previous year when recruiting.

Exclusion Criteria:

• History of cystic fibrosis;
• Hypogammaglobulinaemia;
• Allergic bronchopulmonary aspergillosis;
• Active tuberculosis;
• Subject has been assigned to treatment in a study of the medication under investigation in this study in the previous 6 months.
• Subject has a history of chronic alcohol or drug abuse within the last 6 months.
• Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study.
• Subject has a known hypersensitivity to any components of OM85.
• Recent immunostimulant in last 3 months, cancer, stroke, severe cardiovascular disease, hepatic/kidney impairment, active TB, immuno-related diseases (RA and inflammatory bowel diseases), active ABPA.
• Subjects are free to withdraw from the study at any time, without prejudice to their continued care.
• Subject develops an illness that would interfere with his/her continued participation.
• Subject is noncompliant with the study procedures or medications in the opinion of the investigator.
• Subject takes prohibited concomitant medications as defined in this protocol (flu vaccine and pneumococcal vaccine).
• Subject withdraws his/her consent.
• There will have a confirmation of a pregnancy during the study, as evidenced by a positive pregnancy test.
• The sponsor or a regulatory agency requests withdrawal of the subject.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OM-85; The subjects will be randomly received two courses of 7mg of OM-85 to take one oral capsule per day for 10 days a month for 3 consecutive months at the beginning of the study, then 3 months later with the same schedule for 1 year.	Drug: OM-85 BV; two courses of 7mg of OM-85 or matching placebo to take one oral capsule per day for 10 days a month for 3 consecutive months at the beginning of the study, then 3 months later with the same schedule for 1 year.; Other Names: Bronchovaxom
Placebo Comparator: Placebo; The subjects will be randomly received two courses of 7mg of matching placebo to take one oral capsule per day for 10 days a month for 3 consecutive months at the beginning of the study, then 3 months later with the same schedule for 1 year.	Drug: OM-85 BV; two courses of 7mg of OM-85 or matching placebo to take one oral capsule per day for 10 days a month for 3 consecutive months at the beginning of the study, then 3 months later with the same schedule for 1 year.; Other Names: Bronchovaxom

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchiectasis Exacerbation	the proportion of acute exacerbations	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Life Quality	(1)St George' s Respiratory Questionnaire (SGRQ); (2)Leicester Cough Questionnaire (LCQ)	1 year
Lung Function	Lung function parameters: FEV1, FVC, FEV1/FVC;	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rescue Medication	Use of antibiotics and rapid-acting bronchodilator	1 year

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Collaborators: Peking University; Wenzhou Medical University; China Medical University, China; Tongji University; Zhejiang University; Capital Medical University; Tianjin Medical University
• Investigators: Principal Investigator: Jinming Gao, M.D., Peking Union Medical College Hospitak

Publications and helpful links

General Publications

• Gao J, Gao X, Kong L. To investigate the prevention of OM-85 on bronchiectasis exacerbations (iPROBE) in Chinese patients: study protocol for a randomized controlled trial. Trials. 2014 Apr 29;15:150. doi: 10.1186/1745-6215-15-150.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): November 23, 2018
• Study Completion (Actual): November 23, 2018

Study Registration Dates

• First Submitted: October 17, 2013
• First Submitted That Met QC Criteria: October 19, 2013
• First Posted (Estimate): October 24, 2013

Study Record Updates

• Last Update Posted (Actual): April 21, 2020
• Last Update Submitted That Met QC Criteria: April 17, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: OM-85, bronchiectasis, placebo, acute exacerbation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Broncho-Vaxom
• Other Study ID Numbers: Bronchiectasis-Gao001; Vifro pharmaceuticals (Other Grant/Funding Number: PUMCHGao001)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No