| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10011763 |
| E.1.2 | Term | Cystic fibrosis lung |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• To identify the most efficacious dose of OligoG as defined by the relative change in % Forced Expiratory Volume in one second (FEV1) after 12 weeks. The safety of this dose will also be assessed; the dose with the highest efficacy and most favourable safety profile will be selected for part 2.
• To determine the efficacy of the dose of OligoG selected in part one after 26 weeks of treatment.
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| E.2.2 | Secondary objectives of the trial |
• To compare the safety profiles of OligoG and placebo in patients with CF during 6 months (26 weeks) treatment.
• To document the long term safety of OligoG during 12 months (52 weeks) treatment.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Confirmed diagnosis of Cystic Fibrosis (CF) defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis or genotypic confirmation of CFTR mutation.
• Age 12 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).
• A documented history of chronic Pseudomonas aeruginosa (PA)
infection
• History of antibiotic treatment due to PA infection (not for eradication therapy) during the last 12 months
• Concomitant treatment with inhaled tobramycin, colistin, aztreonam or levofloxacin (either cycled or continuous) for at least 3 months at screening to treat PA infection. In case of cycled inhaled antibiotic treatment, randomisation should be done at the start of a new cycle +/- 2 days.
(together with the IMP intake).days.
• 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 serum 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:
o oral, injected, transdermal or implanted hormonal methods of contraception;
o placement of an intrauterine device (IUD) or intrauterine system (IUS);
o 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 (in adolescent patients: parent(s) or legal guardian(s) must be willing to sign the consent form according to the national regulatory requirements and the adolescent patients must be willing to sign the assent form.
• Willing and able to follow the study procedures. |
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| E.4 | Principal exclusion criteria |
• Use of hypertonic saline more than 2 times a day. If hypertonic saline is used, IMP inhalation should be taken 15 minutes after completion of hypertonic saline therapy.
• Use of CFTR modulator therapies.
• Clinically significant abnormal findings or any value > 3x the upper normal limit of haematology or clinical chemistry parameters, except for the inflammation marker C-reactive protein (CRP), as CRP is standardly increased in CF patients. Further exceptions may be allowed in the case of elevated gamma-GT (GGT) values, exceeding this threshold. These GGT cases will be carefully scrutinised alongside other clinical and laboratory data. Following discussion between the medical monitor and the principal investigator to exclude significant liver injury, the subject may be enrolled in the study.
• 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.
• Hypersensitivity (allergic reaction of any grade) to the IMP or to any of the excipients or placebo.
• Patients unable to perform pulmonary function tests according to the ATS/ERS criteria.
• Uncontrolled or unstable acute or 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.
• History of, or planned organ transplantation.
• Lung infection with Burkholderia cepacia complex or 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:
a) The subject has not had a respiratory tract culture positive for these organisms within the 12 months before the date of informed consent, and
b)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.
• Allergic bronchopulmonary aspergillosis (ABPA) in the last 12 months prior to the Screening Visit, defined as having 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 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. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part 1: Baseline to 12 weeks of treatment
Part 2: Baseline to 26 weeks of treatment |
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| E.5.2 | Secondary end point(s) |
- Absolute change in % predicted FEV1
- Forced Vital Capacity (FVC), Mean Forced Expiratory Flow between 25% and 75% (FEF25-75) of FVC, Peak Expiratory Flow (PEF)
- Rate of Pulmonary Exacerbations
- Culture microbiology including Pseudomonas aeruginosa density in expectorated sputum
- Sputum rheology
- Quality of Life (CFQ-R)
- Patient drug compliance
- Lung Clearance Index (LCI)
- BMI |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Baseline and end of treatment |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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