Clinical trial NCT02157922: A Phase IIb Study of OligoG in Subjects With Cystic Fibrosis
Official title: A Double-blind, Randomized, Placebo-controlled Cross Over Study of Inhaled Alginate Oligosaccharide (OligoG) Administered for 28 Days in Subjects With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic fibrosis
mucolytic
mucociliary clearance
lung clearance
Lead sponsor: AlgiPharma AS
Sponsor class: INDUSTRY
Collaborators: name: Eurostars
name: Smerud Medical Research International AS
First posted: 2014-06-06
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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

1. To demonstrate the safety and tolerability of inhaled OligoG as a dry powder for inhalation after multiple dose administration; and
2. 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.

Eligibility criteria: Inclusion Criteria:

* Male or female with a confirmed diagnosis of cystic fibrosis defined by:

  1. Clinical features consistent with the diagnosis of CF AND Sweat chloride ≥60 mmol/L by pilocarpine iontophoresis; OR
  2. 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.

Primary outcomes:
measure: FEV1 (Forced Expiratory Volume in 1 second)
timeFrame: 28 days, i.e. start and end of treatment periods
Secondary outcomes:
measure: Mucociliary and cough clearance
timeFrame: 28 days, i.e. start and end of treatment periods
Other outcomes:
measure: Safety
timeFrame: Screening, day 0, 14, 28, 56, 70, 84 and follow up
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Berlin
country: Germany
facility: Pediatric Pulmonology and Immunology, Charité Universitätsmedizin
city: Cologne
country: Germany
facility: CF Zentrum Köln, Universitätskrankenhaus Köln
city: Frankfurt
country: Germany
facility: Medizinische Klinik I, Pneumologie, Uniklinik
city: Hannover
country: Germany
facility: Klinik für Pneumologie, CF-Ambulanz
city: Münich
country: Germany
facility: Mukoviszidose-Zentrum für Erwachsene, Med. Klinik V-Innenstadt (LMU)
city: Münich
country: Germany
facility: Pneumologische Praxis Pasing
city: Tübingen
country: Germany
facility: Center for Pediatric Clinical Studies,
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Gothenburg
country: Sweden
facility: CF-mottagningen, Sahlgrenska Universitetssjukhuset
city: Stockholm
country: Sweden
facility: Stockholm CF-center, Karolinska Universitetssjukhuset
city: Belfast
country: United Kingdom
facility: Regional Respiratory Centre, Belfast City Hospital
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
city: Glasgow
country: United Kingdom
facility: Bio-Images Research Ltd, Basement Medical Block, Within GRI
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital
city: London
country: United Kingdom
facility: Royal Brompton and Harefield NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Tacjana Pressler, PhD MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hurley MN, Smith S, Forrester DL, Smyth AR. Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis. Cochrane Database Syst Rev. 2020 Jul 16;7(7):CD008037. doi: 10.1002/14651858.CD008037.pub4.