To evaluate the safety and efficacy of a 14-day course vs a 28 day course of AZLI 75 mg three times a day (TID) in subjects with new onset PA respiratory tract colonization/infection as determined by PA eradication over a 28-day post treatment…
ID
Source
Brief title
Condition
- Respiratory disorders congenital
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the safety and efficacy of a 14-day course vs a 28-day course of
AZLI 75 mg three times a day (TID) in subjects with new onset PA respiratory
tract colonization/infection as determined by PA eradication over a 28-day
post-treatment follow-up period.
Secondary outcome
* To evaluate the time from primary eradication to PA recurrence over a
108-week post-treatment follow-up period
* To compare the efficacy of AZLI 75 mg TID for 14 days vs historical pooled
tobramycin nebulizer solution (TNS) two times a day (BID) for 28 days as
determined by PA eradication over a 28-day post-treatment follow-up period
* To evaluate the time to PA recurrence for a sub-group of subjects matching
the population in the TNS ELITE Study over a 108-week post-treatment follow-up
period
Background summary
Chronic PA infection has devastating consequences for CF patients, in terms of
persistent pulmonary symptoms, frequent acute pulmonary exacerbations often
requiring hospitalization and treatment with IV antibiotics, and progressive
lung function. Prior to the establishment of chronic infection, there is an
opportunity to eradicate new onset PA infection with inhaled anti-pseudomonal
antibiotic treatment, with the goal of delaying the onset of chronic PA
infection. This can preserve lung function, reduce symptom progression, and
prolong survival.
The PA eradication rates in previous study have demonstrated the ability of a
28-day treatment course of AZLI to eradicate new onset PA infection, with rates
comparable to other regimens of inhaled antibiotics.
If the 2 treatment arms are shown to be similar in the ability to eradicate new
onset PA, this will support shorter treatment duration for initial eradication
treatment with AZLI, and will be of benefit to pediatric CF patients (and
parents/caregivers) in terms of reduced treatment burden and improved adherence
to this treatment regimen.
Study objective
To evaluate the safety and efficacy of a 14-day course vs a 28 day course of
AZLI 75 mg three times a day (TID) in subjects with new onset PA respiratory
tract colonization/infection as determined by PA eradication over a 28-day post
treatment follow-up period.
Study design
This is a randomized, double-blind, multi-center study in pediatric subjects
age 3 months to less than 18 years with CF and newly detected PA respiratory
tract colonization/infection. The study schedule will consist of a minimum of
13 visits: Screening, Day 1 (Baseline and Randomization), Day 29, Weeks 6, 8,
16, and at 12 week intervals thereafter through Week 112. Subjects may be
screened up to 14 days prior to the Baseline visit to determine eligibility for
participation in the study. Screening and Baseline may occur on the same day
for subjects.
Initial Eradication Phase (Primary Endpoint):
At the Baseline visit (Day 1), eligible subjects will be randomized to a 28-day
course of AZLI 75 mg TID or a 14-day course of AZLI 75 mg TID followed by a 14
day course of placebo TID. Note: For the purpose of this protocol, AZLI and
placebo will both be considered *study drug treatment*. After completing study
drug treatment, subjects will be followed through Week 8 for safety and
recurrence of PA (cultures obtained at Day 29, Week 6, and Week 8).
Follow-Up Culture Phase:
Following the end of the Initial Eradication Phase, subjects will continue in
the Follow-Up Culture Phase, with study visits and PA cultures obtained at week
16 and then every 12 weeks for 112 weeks total study duration.
Re-Treatment Phase:
Subjects with PA recurrence after study drug treatment should be re treated
with a standard of care antipseudomonal antibiotic regimen at the discretion of
the Investigator.
For the first PA recurrence, subjects will be followed and re-cultured at the
end of re treatment, 4 weeks post re-treatment, and every 12 weeks thereafter
through Week 112. If subjects have subsequent PA recurrences post re-treatment
they will be treated at the Investigator*s discretion and have continued
follow-up cultures collected every 12 weeks through Week 112.
The total study period will be 112 weeks (4 weeks study drug treatment + 4
weeks Initial Eradication Phase + 104 weeks Follow Up Culture Phase).
Intervention
There is a 50% chance to receive AZLI for 28 days and a 50% chance to receive
AZLI for 14 days and placebo for another 14 days.
Study burden and risks
The sudy drug and study procedures are associated with certain risks. These are
described in the ICF. The study drug and the study procedures and the
combination thereof, can also lead to other, unknown risks. The subjects are
carefully monitored. If necessary, the study drug dosage will be decreased or
administration wil be stopped.
Lakeside Drive 333
Foster City 94404
US
Lakeside Drive 333
Foster City 94404
US
Listed location countries
Age
Inclusion criteria
* Male or female aged 3 months to less than 18 years
* Diagnosis of CF as determined by the 2008 CF Consensus Conference criteria:
o Sweat chloride level * 60 mEq/L by quantitative pilocarpine iontophoresis;
o or a genotype with 2 identifiable mutations consistent with CF;
o or an abnormal nasal transepithelial potential difference (NPD), and 1 or
more clinical features consistent with CF
* Documented new onset of positive respiratory tract culture for PA within 30
days of Screening defined as either first lifetime documented PA positive
culture, or PA recovered after at least a 2-year history of PA-negative
respiratory cultures (at least 2 cultures per year)
* FEV1 * 80% predicted (for subjects * 6 years of age who can reliably perform
spirometry assessments)
* Clinically stable with no evidence of either acute significant respiratory
symptoms that would require administration of IV antipseudomonal antibiotics,
oxygen supplementation, or hospitalization
Exclusion criteria
* Use of IV or inhaled antipseudomonal antibiotics within 2 years of Screening
* Use of oral antipseudomonal antibiotics for a respiratory event within 30
days of study entry (Screening visit)
* History or intolerance to inhaled short acting *2 agonists
* History of lung transplantation
* Current requirement for daily continuous oxygen supplementation or
requirement of more than 2 L/minute at night
* Hospitalization for a respiratory event within 30 days prior to Screening
* Changes in bronchodilator, corticosteroid, dornase alfa, or hypertonic saline
medications within 7 days prior to Screening; for subjects on a stable regimen
of hypertonic saline (28 days on/28 days off), beginning or ending a cycle of
hypertonic saline is allowed
* Changes in physiotherapy technique or schedule within 7 days prior to
Screening
* Abnormal renal or hepatic function results at most recent test within the
previous 12 months, defined as
o AST or ALT >5 times upper limit of normal (ULN), or
o Serum creatinine > 2 times ULN for age
* Presence of a condition or abnormality that would compromise the subject*s
safety or the quality of the study data, in the opinion of the Investigator
* Known hypersensitivity to aztreonam, its metabolites, or formulation
excipients in AZLI
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-002749-42-NL |
| CCMO | NL60140.078.17 |