A phase IIb study of OligoG in subjects with cystic fibrosis colonized with Burkholderia spp.

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2014-002125-35-DE
• Date of registration: 21/07/2014
• Prospective Registration: Yes
• Primary sponsor: Algipharma AS
• Public title: A phase IIb study of OligoG in subjects with cystic fibrosis colonized with Burkholderia spp.
• Scientific title: A randomized double-blind, placebo-controlled cross-over study of inhaled alginate oligosaccharide (OligoG) for 28 days in subjects with Cystic Fibrosis using aztreonam due to chronic colonization with Burkholderia spp. - A phase IIb study of OligoG in subjects with cystic fibrosis colonized with Burkholderia spp.
• Date of first enrolment: 18/12/2014
• Target sample size: 12
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002125-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Contacts

• Name: CRO
• Affiliation: SMERUD Medical Research

• Name: CRO
• Affiliation: SMERUD Medical Research

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female with a confirmed diagnosis of cystic fibrosis defined by:
a. Clinical features consistent with the diagnosis of CF (Rosenstein BJ and Cutting GR 1998); and sweat chloride =60 mmol/L by pilocarpine iontophoresis;
or
b. Genotypic confirmation of CFTR mutation
2. Aged 18 years or older
3. Expected ability and willingness to provide sputum samples for microbiological evaluation throughout the study either spontaneously or induced by means of using inhaled hypertonic saline.
4. Chronic colonization with Burkholderia spp. defined as at least two positive microbiological cultures in expectorated sputum within the last 12 months prior to Visit 1.
5. Use of inhaled aztreonam three times daily in a 4 weeks on/off cycle treatment regimen or a continuous intake regimen for at least 4 weeks before screening Visit. For on/off cycles, the Screening Visit (Day -28 to Day -7) should take place in the “off” phase. Randomization Visit (Day 0) should take place the first day “on” to harmonize the aztreonam inhalation period with the IMP intake period.
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. In case lab values exceed 3x the upper limit, the subject will be excluded, as per exclusion criterion 10, below.
7. FEV1 must, at Screening (Visit 1), be greater than 25% of the predicted normal value following adjustment for age, gender, and height according to the Global Lung Initiative (Quanjer PH et al 2012).
8. 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:
oral, injected or implanted hormonal methods of contraception; or
placement of an intrauterine device (IUD) or intrauterine system (IUS);
or
barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
9. Provision of written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion criteria:
1. Changes in underlying therapy (e.g., chest physiotherapy, bronchodilators, NSAIDs, pancreatic enzyme preparations, nutritional supplements and DNase within the 14 days prior to Day 0 (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 112 (Visit 8).
2. Changes in physiotherapy technique or schedule within 14 days prior to Day 0 (Visit 2).
3. Concomitant use of inhaled mannitol or hypertonic saline within 7 days prior to Day 0 (Visit 2); see also section 5.6.
4. Concomitant use of inhaled antibiotics other than aztreonam.
5. Pulmonary exacerbation within 28 days of Screening (Visit 1).
6. Lactose intolerance/milk allergy. A skin test for milk allergy will be performed for lactose intolerance unknowns at screening. Subjects who have previously received inhaled formulations containing lactose without any allergic or tolerance issues are allowed to proceed without a skin test. For subjects demonstrating a positive skin prick test for milk allergy but have no problems eating milk and lactose products, the decision to exclude will be at the investigator’s discretion.
7. 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 0 (Visit 2).
8. History of, or planned organ transplantation.
9. Active allergic bronchopulmonary aspergillosis (ABPA) in the last 12 months prior to Screening (Visit 1), defined as having received pharmacological treatment for ABPA.
10. Clinically significant abnormal findings or any value = 3 x the upper limit of normal on haematology or biochemistry
11. Subjects unable to perform pulmonary function tests according to the ATS/ERS criteria.
12. Pregnant or breast-feeding women. A negative urine pregnancy test must be demonstrated in females of child-bearing potential at Screening (Visit 1).
13. Subjects who have participated in any clinical trial within the 28 days (or shorter than 5 half-lives of the investigational drug) prior to Screening (Visit 1).
14. Subjects with documented or suspected clinically significant, alcohol or drug abuse as per Investigator’s discretion.
15. Current malignant disease (with the exception of basal cell carcinoma; BCC).
16. Any serious or active illness incl. psychiatric diseases, which in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol.
17. Subjects not willing/able to follow the study instructions.
18. Resistance to aztreonam.
19. Intolerance to aztreonam or any of its excipients.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Cystic Fibrosis

Intervention(s)

Product Name: OligoG CF-5/20
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Oligomer of Sodium Alginate
Current Sponsor code: OligoG
Other descriptive name: OLIGOG CF-5/20
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 35-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Secondary Objective: To explore the effect of inhaled OligoG on various efficacy variables such as lung function, Quality-of-Life, rheology and other microbiological outcome measures.
To evaluate the safety, tolerability and patient compliance with treatment.

Primary end point(s): Change in density of Burkholderia spp. in expectorated sputum from baseline to the end of treatment (and any other visit), as measured by culture independent techniques.

Timepoint(s) of evaluation of this end point: Baseline and day 28 of each treatment period

Main Objective: To explore the efficacy of OligoG in reducing the microbial burden of Burkholderia spp. as measured in expectorated sputum samples.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline and day 28 of each treatment period

Secondary end point(s): Change in sputum rheology from baseline to the end of treatment (and any other visit).
Change in lung function tests from baseline to the end of treatment (and any other visit).
Change in Quality of Life by CFQ-R from baseline to the end of treatment (and any other visit).
Changes in MIC of aztreonam for other bacteria isolated by culture methods from sputum samples.

Secondary ID(s)

SMR-2591

Source(s) of Monetary Support

Eurostars

Algipharma AS

Smerud Medical Research