A Study of OligoG in Cystic Fibrosis Subjects With Burkholderia Spp. Infection

Study Overview
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Brief Summary
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The purpose of the study is to assess the efficacy of Alginate oligosaccharide (OligoG) dry powder for inhalation in cystic fibrosis (CF) patients with a Burkholderia spp. infection.

Detailed Description
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Primary objective: To explore the efficacy of inhaled OligoG in reducing the microbial burden of Burkholderia spp. as measured in expectorated sputum samples. Secondary objectives: To explore the effect of inhaled OligoG on various efficacy variables such as lung function, Quality-of-Life, rheology and other microbiological outcome measures. To evaluate the safety, tolerability and subject compliance with treatment The study will also evaluate the effect of inhaled OligoG on various efficacy variables such as lung function, Quality-of-Life, rheology and other microbiological outcome measures, and evaluate the safety and patient compliance with treatment.

Official Title
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A Randomized Double-blind, Placebo-controlled Cross-over Study of Inhaled Alginate Oligosaccharide (OligoG) for 28 Days in Subjects With Cystic Fibrosis Using Aztreonam Due to Chronic Colonization With Burkholderia Spp.

Conditions
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Cystic Fibrosis, Burkholderia Infection

Intervention / Treatment
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* Drug: Alginate oligosaccharide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female with a confirmed diagnosis of cystic fibrosis defined by: Clinical features consistent with the diagnosis of CF; AND Sweat chloride ≥60 mmol/L by pilocarpine iontophoresis; OR Genotypic confirmation of CFTR mutation Aged 18 years or older Ability to provide sputum samples for microbiological evaluation throughout the study either spontaneously or induced. Chronic colonization with Burkholderia spp. defined as at least two positive microbiological cultures in expectorated sputum within the last 12 months from Visit 1. Use of inhaled aztreonam three times daily in a 4 weeks on/off cycle treatment regimen or a continuous intake regimen for at least 4 weeks before screening visit. For on/off cycles, screening visit should take place in the off phase. Randomization visit should take place the first day on to harmonize the aztreonam inhalation period with the IMP intake period. Willingness to stop treatment with other inhaled antibiotics. At Screening no clinical or laboratory findings suggestive of significant pulmonary illness, other than CF, which in the opinion of the investigator would preclude participation in the study. FEV1 greater than 25% of the predicted normal value following adjustment for age, gender, and height according to the Global Lung Initiative Female subjects of child bearing potential and male subjects participating in the study who are sexually active must use acceptable contraception. Female subjects documented as being of non-child-bearing potential are exempt from the contraceptive requirements. Provision of written informed consent. Exclusion Criteria: Changes in underlying therapy within the 14 days prior to Day 0. Subjects must be willing to remain on the same underlying stable therapy regimens for the duration of the study until the final follow-up visit at Day 98. Changes in physiotherapy technique or schedule within 14 days prior to Day 0. Prohibited medications within 7 days prior to Day 0. Concomitant administration of inhaled mannitol or hypertonic saline within 7 days prior to Day 0. Concomitant use of inhaled antibiotics other than aztreonam. Pulmonary exacerbation within 28 days of Screening. Lactose intolerance/milk allergy. On-going acute illness. Subjects must not have needed an outpatient visit, hospitalization or required any change in therapy for other pulmonary disease between Screening and Day 0. History of, or planned organ transplantation. Active allergic bronchopulmonary aspergillosis (ABPA) in the last 12 months prior to Screening, defined as having received treatment for ABPA. Inability or unwillingness to provide sputum samples for microbiological evaluation throughout the study either spontaneously or induced by means of using inhaled hypertonic saline. Clinically significant abnormal findings on haematology or clinical chemistry. In addition, any value ≥ 3 x the upper limit of normal will exclude the subject from participating in the study. Subjects unable to perform pulmonary function tests according to the ATS/ERS criteria. Pregnant or breast-feeding women. A negative urine pregnancy test must be demonstrated in females of child-bearing potential at Screening. Subjects who have participated in any interventional clinical trial within the 28 days prior to Day 0. Subjects with documented or suspected, clinically significant, alcohol or drug abuse, as determined by the Investigator. Current malignant disease (with the exception of basal cell carcinoma; BCC). Any serious or active medical or psychiatric illness, which in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol. Patients not willing/able to follow the study instructions. Resistance to aztreonam, or intolerance to aztreonam or any of its excipients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alginate oligosaccharide<br>Inhalation of a dry powder OligoG in the first treatment period, and placebo in the second period | Drug: Alginate oligosaccharide<br>* Inhalation of dry powder for inhalation (DPI)<br>* Other names: OligoG;|
| Placebo Comparator: Placebo<br>Inhalation of placebo dry powder in the first treatment period, and OligoG in the second period | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Burkholderia spp. density in expectorated sputum and/or induced sputum. |  | 28 days, i.e. at start and end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical safety as measured by vital signs | Measurement of vital signs | Time Frame: Screening, day 0, 14, 28, 56, 70, 84 and follow up at day 112 | 
| Clinical safety as measured by ECG | Measurement of ECG | Time Frame: Screening, day 0, 14, 28, 56, 70, 84 and follow upat day 112 | 
| Clinical safety as measured by blood oxygen saturation | Measurement of blood oxygen saturation | Time Frame: Screening, day 0, 14, 28, 56, 70, 84 and follow upat day 112 | 
| Clinical safety as measured by FEV1 (Forced Expiratory Volume in 1 second) | Measurement of pulmonary function tests | Time Frame: Screening, day 0, 14, 28, 56, 70, 84 and follow up at day 112 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cystic fibrosis, alginate oligosaccharide, Burkholderia, aztreonam