A Phase 2b Randomised, Placebo Controlled Study of OligoG in Patients with Cystic Fibrosis

• Genotypic confirmation of CFTR mutation or clinical diagnosis of Cystic Fibrosis (CF) confirmed by a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis.
• Age 18 years or older.
• Male or female patients with any ethnicity.
• FEV1 at screening in the range of ≥40% and 90% of the predicted normal for age, sex, and height, according to the GLI equation (Eur Respir J. Dec 2012; 40(6): 1324-1343).
• History of Pseudomonas aeruginosa (PA) infection with at least one positive microbiological PA testing during the last 12 months before the Screening Visit.
• History of antibiotic treatment due to PA infection (not for eradication therapy) during the last 12 months
• Concomitant treatment with inhaled tobramycin, colistin, or aztreonam (either cycled or continuous) for at least 3 months at screening to treat PA infection. In case of cycled antibiotic treatment, the treatment should start with an active cycle at the day of randomisation (+/- 2 day) (together with the IMP intake). If taking tobramycin cycled with another antibiotic, IMP should start on the active cycle of tobramycin.
• Stable CF disease as judged by the investigator.
• Willing to remain on a stable CF medication regimen (standard of care; SOC) during the study.
• Women of child-bearing potential must have a negative urine pregnancy test at the Screening and Randomisation Visit.

• Male and female patients must use acceptable contraceptive methods for the duration of the study. Male and female patients without child-bearing potential (i.e. who are infertile, surgically sterile or post-menopausal) are exempted from the contraceptive requirements. For the purpose of this study acceptable contraception is defined as one or a combination of the following:

  • oral, injected, transdermal or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
• Capable of inhaling dry powder.
• Willing to sign informed consent
• Willing and able to follow the study procedures.

Exclusion Criteria:

• Use of hypertonic saline more than 2 times a day. If hypertonic saline is used, OligoG inhalation should be taken at least 15 minutes after completion of hypertonic saline therapy.
• Use of CFTR modulator therapies.

• Clinically significant abnormal findings of haematology or clinical chemistry;

  • Elevated gamma GT (GGT), ALT, or AST > 3x the upper normal limit of normal (ULN)
  • Bilirubin >2x ULN
  • Abnormal renal function, with a creatinine clearance calculated \<50ml/min
  • Haemoglobin \<10g/dL
• History of any comorbidity that, in the opinion of the investigator, might distort the results of the study or cause an additional risk in administering study drug to the patient.
• Pulmonary exacerbation within 28 days prior to randomisation.
• Change in CF therapy within 28 days before randomisation (first dose of IMP).
• Pregnant or breastfeeding females.
• History of allergic reactions to the ingredients of the IMP according to Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4, including lactose and milk protein.
• Patients unable to perform pulmonary function tests according to the ATS/ERS criteria.
• Uncontrolled or unstable chronic diseases (e.g. congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations) that would limit the compliance with study requirements in the opinion of the investigator.
• Any acute illness in the last 14 days
• History of, or planned organ transplantation.

• Lung infection with organisms associated with a more rapid decline in pulmonary status (including, but not limited to Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus). For subjects who have had a history of a positive culture, the following criteria will be used to determine whether the subject is free of infection with such organisms:-

  • The subject has not had a respiratory tract culture positive for these organisms within the 12 months before the date of informed consent, and
  • The subject has had at least 2 respiratory tract cultures negative for such organisms within the 12 months before the date of informed consent, with the first and last of these separated by at least 3 months, and the most recent one within the 6 months before the date of informed consent.
• Active allergic bronchopulmonary aspergillosis (ABPA) in the last 12 months prior to the Screening Visit, that has received pharmacological treatment for ABPA.
• Requirement for continuous (24 hour/day) oxygen supplementation.
• Patients currently receiving any other investigational treatment, or who have participated in a clinical study within 4 weeks (28 days) prior to the screening visit.
• Current malignant disease (with the exception of basal cell carcinoma and cervical neoplasia).
• Any medical or psychological condition, other than CF, which in the opinion of the investigator exposes the patient to an unacceptably high risk.
• Patients with documented or suspected, clinically significant, alcohol or drug abuse as per Investigator's discretion.