A Phase IIb Study of OligoG in Subjects With Cystic Fibrosis

Study Overview
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Brief Summary
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The purpose of the study is assessment of efficacy and safety of OligoG as a dry powder formulation, in adult subjects with cystic fibrosis.

Detailed Description
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The primary objective is to demonstrate efficacy of inhaled OligoG measured by FEV1, and supported by secondary endpoints including Mucociliary Clearance, rheology,microbiology and Quality-of-Life. The secondary objectives are To demonstrate the safety and tolerability of inhaled OligoG as a dry powder for inhalation after multiple dose administration; and To evaluate patient compliance with treatment. The design will be randomized, double-blind, placebo-controlled, multi-center, cross-over phase II study. Mucociliary and Cough clearance (MCC) will be an exploratory endpoint in a subset of 24 patients, and Lung Clearance Index (LCI) an exploratory endpoint in another subset of 20 or more patients.

Official Title
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A Double-blind, Randomized, Placebo-controlled Cross Over Study of Inhaled Alginate Oligosaccharide (OligoG) Administered for 28 Days in Subjects With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: alginate oligosaccharide


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 Positive microbiological finding of Pseudomonas aeruginosa in expectorated sputum or cough swab within 24 months prior to Screening FEV1 between 40%-100% At Screening no clinical or laboratory findings suggestive of significant pulmonary illness, other than CF Female subjects of child bearing potential and sexually active male subjects must use contraception Provision 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. Changes in physiotherapy technique or schedule within 14 days prior to Day 0. Prohibited medications within 7 days prior to Day 0. Pulmonary exacerbation within 28 days of Screening. Positive microbiological finding of Burkholderia sp. in expectorated sputum or cough swab documented within 12 months prior to 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. Treatment for Allergic bronchopulmonary aspergillosis (ABPA). Requirement for continuous (24 hour/day) oxygen supplementation. Diagnosed with the G551D-mutation, and currently on concomitant treatment with Ivacaftor (Kalydeco). Concomitant administration of inhaled mannitol or hypertonic saline within 7 days prior to Day 0 (Visit 2). Initiation of cycled, inhaled tobramycin (TOBI) and Colistin less than 4 months prior to Screening (Visit 1). Note: Chronic TOBI and Colistin users are allowed to participate in this study, but subjects who have recently initiated chronic TOBI or Colistin should have at least 2 cycles of TOBI or Colistin respectively in the preceding 4 months before being enrolled in this study. Treatment should be phased in line with the antibiotic treatment. Concomitant use of all other marketed antibiotic agents is permitted, providing subjects are willing to remain on the same regimens within the 28 days immediately prior to Day 0 and for the entire duration of the study (until the follow-up visit). 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 (Section 4.2.9) at Screening. Subjects who have participated in any interventional clinical trial within the 28 days prior to Day 0 (Visit 2). Subjects with documented or suspected, clinically significant, alcohol or drug abuse. Current malignant disease (with the exception of basal cell carcinoma and cervical neoplasia). 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. DPI intolerance, active or placebo For MCC sites only: Smoking. A negative Cotinine test must be demonstrated at Screening Subjects who have any non-removable metal objects such as metal plates, screws etc in their head, neck, chest or abdominal area Subjects for whom participation in this study will exceed the limits of total radiation exposure allowed in any 12 month period (5 mSv), or will exceed 10 mSv over any three year period.

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 of placebo the second period | Drug: alginate oligosaccharide<br>* Inhalation<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: alginate oligosaccharide<br>* Inhalation<br>* Other names: OligoG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 (Forced Expiratory Volume in 1 second) | An improvement in FEV1 during treatment with OligoG as compared to placebo is the primary endpoint of the study. | 28 days, i.e. start and end of treatment periods | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucociliary and cough clearance | Mucociliary clearance is assessed by measuring the movement of an inhaled radiotracer up the airways. | 28 days, i.e. start and end of treatment periods | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic fibrosis, mucolytic, mucociliary clearance, lung clearance