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] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
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 |
The principle research objective is:
To determine the safety and local tolerability of multiple dose administration of inhaled OligoG in subjects with cystic fibrosis. Particular emphasis will be put on local, clinical tolerance, lung function and adverse events related to lung function. |
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E.2.2 | Secondary objectives of the trial |
The secondary research objectives are:
The effect of multiple dose administration of inhaled OligoG on various efficacy variables will also be explored, such as break up of mucus structure, lung function, respiratory symptoms, Quality-of-Life and microbiological outcome measures. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to participate in the study subjects must meet all of the following inclusion criteria:
1) Male or female with a confirmed diagnosis of cystic fibrosis defined by:
a. Clinical features consistent with the diagnosis of CF AND
b. Sweat chloride ≥60 mmol/L by pilocarpine iontophoresis; OR
c. Genotypic confirmation of CFTR mutation
2) Aged 18 years or older
3) Ability to provide samples for microbiological evaluation throughout the study. Note: sputum samples are preferred however cough swabs may be performed on occasions where sputum cannot be collected.
4) Positive microbiological finding of Pseudomonas aeruginosa in expectorated sputum or cough swab documented within 24 months prior to Screening (Visit 1).
5) FEV1 must, at Screening (Visit 1), be between 35%-80% of the predicted normal value following adjustment for age, gender, and height according to the Knudson equation.
6) At Screening (Visit 1), 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
7) 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. For the purpose of this study acceptable contraception is defined as:
a. oral, injected or implanted hormonal methods of contraception; OR
b. placement of an intrauterine device (IUD) or intrauterine system (IUS); OR
c. barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
8) Provision written informed consent
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E.4 | Principal exclusion criteria |
In order to participate in the study subjects must not meet any of the following exclusion criteria
1) Changes in underlying therapy (e.g., pulmonary massage therapy, bronchodilators, NSAIDs, antibiotic agents, pancreatic enzyme preparations, nutritional supplements and DNase within the 21 days prior to Day 1 (Visit 2). 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 111.
2) Changes in physiotherapy technique or schedule within 14 days prior to Day 1 (Visit 2).
3) Prohibited medications within 7 days prior to Day 1 (Visit 2).
4) Pulmonary exacerbation within 28 days of Screening (Visit 1)
5) Positive microbiological finding of Burkholderia sp. in expectorated sputum or cough swab documented within 12 months prior to Screening (Visit 1).
6) 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 (Visit 1) and Day 1 (Visit 2).
7) History of, or planned organ transplantation.
8) Allergic bronchopulmonary aspergillosis (ABPA) in the last 12 months prior to Screening (Visit 1), defined as having received treatment for ABPA.
9) Requirement for continuous (24 hour/day) oxygen supplementation.
10) Concomitant administration of inhaled mannitol or hypertonic saline within 7 days prior to Day 1 (Visit 2).
11) Initiation of cycled, inhaled tobramycin (TOBI) less than 4 months prior to Screening (Visit 1). Note: Chronic TOBI users are allowed to participate in this study, but subjects who have recently initiated chronic TOBI should have at least 2 cycles of TOBI in the preceding 4 months before being enrolled in this study. Chronic TOBI subjects should be starting an ‘off-TOBI’ period at Day 1 (Visit 2) so there will be no concomitant dosing of TOBI and assigned study medication.
12) 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.
13) Subjects unable to perform pulmonary function tests according to the ATS/ERS criteria.
14) Pregnant or breast-feeding women. A negative urine pregnancy test must be demonstrated in females of child-bearing potential at Screening (Visit 1).
15) Subjects who have participated in any interventional clinical trial within the 28 days prior to Day 1 (Visit 2).
16) Subjects with documented or suspected, clinically significant, alcohol or drug abuse. The determination of clinical significance will be determined by the Investigator.
17) Known allergies or intolerance to alginates (e.g., foods and food additives based on seaweed extracts).
18) Current malignant disease (with the exception of basal cell carcinoma; BCC).
19) 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the safety and local tolerability of multiple dose administration of inhaled OligoG in CF subjects. Particular emphasis will be put on local, clinical tolerance, pulmonary function and pulmonary adverse events. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be evaluated at visits 1, 2, 3, 4, 5, 6, 7, 8, 9 |
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E.5.2 | Secondary end point(s) |
The effect of multiple dose administration of inhaled OligoG on various efficacy variables will also be explored, such as mucolytic activity, lung function, respiratory symptoms, Quality-of-LIfe and microbiological outcome measures. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoint will be evaluated at visits 2, 3, 4, 5, 6, 7, 8, 9 |
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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 | No |
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 | No |
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 | No |
E.8.1.6 | Cross over | Yes |
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 | 2 |
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 | 3 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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Completion of all trial procedures by participants in all countries.
The screening and treatment periods for subjects participating in the study will be approximately 18 weeks (Day -14 to 111). All subjects will in addition be followed for up to 6 months following the last dose of study medication OR until the first post study CF Exacerbation whichever occurs sooner.
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |