A Phase IIb Study of OligoG in Subjects With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

— SMR-2984  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02157922
• Other study ID #: SMR-2984
• Status: Completed
• Phase: Phase 2
• First received: June 4, 2014
• Last updated: April 18, 2018
• Start date: October 2014
• Est. completion date: September 2017

Study information

• Verified date: August 2016
• Source: AlgiPharma AS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: September 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• alginate oligosaccharide
Inhalation

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen
Germany	Pediatric Pulmonology and Immunology, Charité Universitätsmedizin	Berlin
Germany	CF Zentrum Köln, Universitätskrankenhaus Köln	Cologne
Germany	Medizinische Klinik I, Pneumologie, Uniklinik	Frankfurt
Germany	Klinik für Pneumologie, CF-Ambulanz	Hannover
Germany	Mukoviszidose-Zentrum für Erwachsene, Med. Klinik V-Innenstadt (LMU)	Münich
Germany	Pneumologische Praxis Pasing	Münich
Germany	Center for Pediatric Clinical Studies,	Tübingen
Norway	Oslo University Hospital	Oslo
Sweden	CF-mottagningen, Sahlgrenska Universitetssjukhuset	Gothenburg
Sweden	Stockholm CF-center, Karolinska Universitetssjukhuset	Stockholm
United Kingdom	Regional Respiratory Centre, Belfast City Hospital	Belfast
United Kingdom	Papworth Hospital	Cambridge
United Kingdom	Bio-Images Research Ltd, Basement Medical Block, Within GRI	Glasgow
United Kingdom	Liverpool Heart and Chest Hospital	Liverpool
United Kingdom	Royal Brompton and Harefield NHS Foundation Trust	London
United Kingdom	Queens Medical Centre	Nottingham
United Kingdom	Southampton General Hospital	Southampton

Sponsors (3)

Lead Sponsor	Collaborator
AlgiPharma AS	Eurostars, Smerud Medical Research International AS

Countries where clinical trial is conducted

Denmark,  Germany,  Norway,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety	Measurement of vital signs, ECG, blood oxygen saturation and pulmonary function tests. Adverse events and concomitant medications will be recorded, and blood samples will be collected for hematology, clinical chemistry and OligoG concentration.	Screening, day 0, 14, 28, 56, 70, 84 and follow up
Primary	FEV1 (Forced Expiratory Volume in 1 second)	An improvement in FEV1 during treatment with OligoG as compared to placebo is the primary endpoint of the study.	28 days, i.e. start and end of treatment periods
Secondary	Mucociliary and cough clearance	Mucociliary clearance is assessed by measuring the movement of an inhaled radiotracer up the airways.	28 days, i.e. start and end of treatment periods