A Dose-finding Study of Inhaled OligoG vs Placebo in Patients With Cystic Fibrosis

Study Overview
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Brief Summary
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Randomized, double blind, placebo controlled study. The study has two parts: Dose-finding part, followed by longer term follow-up (6 months)

Detailed Description
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Part 1: Randomized, double blind, placebo controlled dose-finding. Patients will be assigned to 1 of 3 doses OligoG, or to placebo, on top of Standard of Care. Patients will be treated for 12 weeks, followed by 4 weeks washout.The primary endpoint is relative change in % predicted FEV1. Secondary endpoints include additional spirometry parameters, exacerbation rate, Quality of Life, sputum rheology and microbiology, safety laboratory tests and adverse event reporting. Part 2: Randomized double-blind 6 -month study, for longer term follow-up of the dose identified in Part 1. New patients will be recruited in part 2, in addition to patients who received placebo in Part 1. In addition to the endpoints studied in Part 1, Part 2 will include Lung Clearance Index (LCI), chest imaging by MRI or CT, and pharmaco-economic parameters.

Official Title
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A Randomized, Double Blind, Dose-finding Study of Inhaled Oligosaccharide (OligoG) vs Placebo in Patients With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: OligoG Dry powder for inhalation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of CF FEV1 at screening >40 and < 90% of predicted normal History of PA infection in last 12 m History of antibiotic treatment due tp PA infection (not for eradication) during last 12 m Concomitant inhaled tobramycin, colistin, aztreonam, or levoflaxin (cycled or continuous) Stable CF disease Willing to remain on stable CF medication (Standard of care) Women of child-bearing potential must habe negative urine pregnany test Males & females must use acceptable contraception Capable of inhaling dry powder willing to sign informed consent willing and able to follow study procedures Exclusion Criteria: Use of hypertonic saline > twice daily Clinically significant abnormal lab findings, except CRP. In case of high GGT values, case will be discussed by experts before deciding History of comorbidity that may distort results or cause additional risk pulmonary exacerbation within 28 days prior to randomisation Change in CF therapy within 28 days prior to randomisation Burkholderia spp. finding within 12 m prior to screening pregnant or breast feeding females History of allergic reactions to IMP ingredients, incl milk protein Inability to perform lung function tests according to ATS/ ERS criteria Uncontrolled or unstable diseases that might limit compliance History of, or planned organ transplantation Allergic ABPA in the last 12 months prior to the screening visit Requirement for continuous oxygen supplementation Current participation in another clinical study medical condition, other than CFwhich exposes the patient to an unacceptably high risk Concurrent mlignant disease, except BCC and cervical neoplasia Clinically significant alcohol or drug abuse

Ages Eligible for Study
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Minimum Age: 12 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: Parallel Assignment
Interventional Model Description: Randomised, double blind, dose-finding
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo DPI<br>Matching placebo dry powder for inhalation. OligoG is replaced by lactose. 10 capsules, BID | Drug: OligoG Dry powder for inhalation<br>* 10 capsules Dry Powder for Inhalation, BID<br>* Other names: Placebo dry powder for inhalation;|
| Active Comparator: Low dose OligoG DPI<br>17.5 mg OligoG dry powder for inhalation. 10 capsules, BID | Drug: OligoG Dry powder for inhalation<br>* 10 capsules Dry Powder for Inhalation, BID<br>* Other names: Placebo dry powder for inhalation;|
| Active Comparator: medium dose OligoG DPI<br>27.5 mg OligoG dry powder for inhalation. 10 capsules, BID | Drug: OligoG Dry powder for inhalation<br>* 10 capsules Dry Powder for Inhalation, BID<br>* Other names: Placebo dry powder for inhalation;|
| Active Comparator: High dose OligoG DPI<br>37.5 mg OligoG dry powder for inhalation. 10 capsules, BID | Drug: OligoG Dry powder for inhalation<br>* 10 capsules Dry Powder for Inhalation, BID<br>* Other names: Placebo dry powder for inhalation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 second (FEV1) | the amount of air a person can forcefully exhale in one second | Change from before to after 12 weeks treatment (Part 1) and 26 weeks (Part 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung Clearance Index (LCI) (Part two only) | Lung clearance index (LCI) measured by multiple breath washout is a sensitive measure of ventilation inhomogeneity. | Change from before to after 26 weeks treatment | 
| Sputum culture microbiology | Reduction in Pseudomonas Aeruginosa CFU Counts and total counts | Change from before to after 12 weeks treatment (Part 1) and 26 weeks (Part 2) | 
| Pulmonary Exacerbations | Acute pulmonary exacerbations | Change from before to after 12 weeks treatment (Part 1) and 26 weeks (Part 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oligosaccharide