Clinical Trial to Assess the Safety and Efficacy of Aztreonam for Inhalation Solution (AZLI) in patients with Cystic Fibrosis (CF) and Chronic Burkholderia Species Infection

• Register: EUCTR
• Last refreshed on: 16 February 2015
• Main ID: EUCTR2009-011740-19-Outside-EU/EEA
• Date of registration: 02/02/2015
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: Clinical Trial to Assess the Safety and Efficacy of Aztreonam for Inhalation Solution (AZLI) in patients with Cystic Fibrosis (CF) and Chronic Burkholderia Species Infection
• Scientific title: Phase 3b Randomized, Double-Blind, Placebo-Controlled Two-Part Trial to Assess the Safety and Efficacy of Continuous Aztreonam for Inhalation Solution (AZLI) in Subjects with Cystic Fibrosis (CF) and Chronic Burkholderia Species Infection
• Target sample size: 100
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011740-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Two-part trial: 24 weeks double-blind placebo controlled followed by 24 weeks open label treatment. If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Canada, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: Gilead Sciences International Ltd

• Name: Clinical Trials Information
• Affiliation: Gilead Sciences International Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female = 6 years of age
2. Subjects with CF as diagnosed by one of the following:
— Documented sweat chloride = 60 mEq/L by quantitative pilocarpine iontophoresis test
— Documented sweat sodium = 60 mmol/L
— Two well characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
— Abnormal NPD with accompanying symptoms characteristic of CF
3. Chronic infection with Burkholderia spp. defined by:
— One sputum (or bronchoalveolar lavage) culture positive for Burkholderia spp. within 6 months prior to baseline assessment,
— At least 50% of sputum (or bronchoalveolar lavage) cultures collected at least one month apart over the previous 12 months prior to baseline assessment positive for Burkholderia spp. (minimum of 2 positive cultures), and
— At least one positive sputum (or bronchoalveolar lavage) culture (obtained at any point in time) confirmed to be Burkholderia spp. by the CFF Burkholderia cepacia Research Laboratory and Repository at the University of Michigan (or equivalent Canadian reference laboratory)

Subjects with oro-pharyngeal cultures rather than sputum culture results available in the previous 12 months will meet the above criteria for chronic infection with Burkholderia spp. if:
— There is at least one documented prior lower respiratory tract culture(s) (expectorated, induced sputum or bronchoalveolar lavage) positive for Burkholderia spp. (obtained at any time point), and
— There is concordance of the species isolated from at least one prior lower respiratory tract cultures (obtained at any time point) and recent oropharyngeal cultures (obtained in the previous 12 months)
4. Concomitant aerosolized antibiotic treatment: subjects receiving intermittent (alternating month on/month off) aerosolized antibiotic treatment are eligible, but must be at least 1 week into their off-treatment cycle at the time of baseline assessment. Subjects receiving continuous aerosolized antibiotic treatment will be eligible without restriction
on their aerosolized antibiotic treatment
5. Chest radiograph, computed tomography (CT) or magnetic resonance imaging (MRI), (most recent, obtained within 90 days of screening) without significant acute findings (e.g., infiltrates [lobar or diffuse interstitial], pleural effusion, pneumothorax), and no significant intercurrent illness; chronic, stable findings (e.g., chronic scarring or atelectasis) are allowed
6. Subjects (and parent/guardian as required) must be able to provide written informed consent/assent prior to any study related procedures
7. Ability to perform reproducible pulmonary function tests
8. Sexually active females of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of study drug; a highly effective method of birth control is defined as a method that results in a low failure rate (i.e., less than 1% per year)
when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), or a vasectomized partner
Are the trial subjects under 18? yes
Number of subjects for this age range: 17
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 83
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Administration of any investigational drug or use of any investigational device within 28 days of randomization/baseline and within six half-lives of the investigational drug (whichever is longer)
2. Administration of AZLI treatment within the 28 days prior to randomization/baseline
3. Known local or systemic hypersensitivity to monobactam antibiotics
4. History of lung transplantation
5. Abnormal renal or hepatic function results at most recent test within the previous 90 days, defined as:
— AST or ALT > 5 times upper limit of normal (ULN) range
— Serum creatinine > 2 times ULN
6. Known portal hypertension or complications of CF hepatopathy
7. Positive urine pregnancy test (confirmed by serum pregnancy test) at screening; all women of childbearing potential will be tested
8. Female of childbearing potential who is lactating or not practicing a highly effective method of birth control as defined in Section 7.8
9. 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


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

Health Condition(s) or Problem(s) studied

Cystic Fibrosis subjects with chronic Burkholderia spp. infection of the airways.
MedDRA version: 17.1 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

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

Intervention(s)

Trade Name: Cayston
Aztreonam 75 mg powder and solvent for nebuliser solution
Pharmaceutical Form: Powder and solvent for nebuliser solution
INN or Proposed INN: AZTREONAM
CAS Number: 78110-38-0
Current Sponsor code: AZLI
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Powder and solvent for nebuliser solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24 of study.

Primary end point(s): The primary endpoint is the relative change from baseline in FEV1 percent predicted as measured by the AUCave through Week 24.

Main Objective: The primary objective is to evaluate the safety and efficacy of continuous AZLI treatment in subjects with CF and Burkholderia spp. infection in the airways.

Secondary Objective: • Effect of continuous AZLI use on microbial resistance
• Suppressive effect of AZLI on Burkholderia spp.
• Safety of AZLI administered TID for up to 48 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24 of study.

Secondary end point(s): • AUCave of relative change from baseline in FEV1, FVC, and FEF25-75 through Week 24
• AUCave of change from baseline in clinical symptoms as assessed by the respiratory symptoms domain of the CFQ-R through Week 24
• AUCave of change from baseline in clinical symptoms as assessed by the non-respiratory domains of the CFQ-R through Week 24
• Change from baseline in BMI at Week 24
• Change from baseline in Burkholderia spp. CFUs in sputum at Week 24
• Use of systemic antibiotics through Week 24 of the study
• Percent of days subjects used systemic antibiotics through Week 24 of the study
• Percent of days subjects were hospitalized through Week 24 of the study
• Percent of days lost from school or work through Week 24 of the study

Secondary ID(s)

GS-US-205-0127

64,402

Source(s) of Monetary Support

Gilead Sciences, Inc.