Clinical trial NCT01316276: Extension Study of Liposomal Amikacin for Inhalation in Cystic Fibrosis (CF) Patients With Chronic Pseudomonas Aeruginosa (Pa) Infection
Official title: Long Term Safety and Tolerability Study of Open-Label Liposomal Amikacin for Inhalation (ARIKACE™) in Cystic Fibrosis Patients With Chronic Infection Due to Pseudomonas Aeruginosa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Respiratory Infections
Pulmonary Cystic Fibrosis
cystic fibrosis transmembrane conductance regulator (CFTR)
Anti-bacterial Agent
Arikayce
ALIS
LAI
Lead sponsor: Insmed Incorporated
Sponsor class: INDUSTRY
First posted: 2011-03-16
Enrollment: 206
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the long term safety and tolerability of Liposomal Amikacin for Inhalation (LAI) 590 mg once daily (QD) in Cystic Fibrosis patients with chronic infection due to pseudomonas aeruginosa. This long-term, open-label, multi-cycle extension study enrolled subjects who had successfully completed study TR02-108, were compliant with the study protocol, and did not meet any of the listed study discontinuation criteria. The safety and tolerability of LAI were evaluated for up to approximately 2 years.

Detailed description: This was a long-term, open-label, multi-cycle extension study for patients in the Phase 3 study TR02-108 and TR02-109 who had successfully completed the 168-day study period and met study safety criteria. As this was a safety and tolerability long-term extension study, no sample size calculations were performed. All patients who completed TR02-108, were compliant with the study protocol, and did not meet any of the criteria listed for study discontinuation (safety reasons or non-compliance) were able to participate in this open-label study.

The end of study visit for TR02-108 was to serve as the baseline study visit (Day 1) for TR02-110 if the patient had signed the informed consent at least 4 days prior to the end of study visit and met all safety criteria for TR02-110. If the end of study visit was not used as the baseline visit, a separate baseline visit (Day 1) was to be performed within 14 days of completing TR02-108.

Patients were to receive a delivered dose of 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles. The study was implemented as 2 consecutive extension periods, each consisting of 48 weeks (approximately 12 months). Patients were re-consented for the second extension period at the completion of the first extension period. The total study period was up to 96 weeks (approximately 2 years).

During the first 28 days of treatment, patients were evaluated at the study site bi-weekly for safety, tolerability and efficacy. Thereafter, for the duration of the study, patients were evaluated at the study site on the first and last days of dosing during the on-treatment periods. During the study, starting with the off-treatment period of Cycle 1, patients were contacted by telephone once during every 28-day period to assess safety. A final site visit occurred 28 days after last dose of LAI. Arikace™, Arikayce™,Liposomal Amikacin for Inhalation (LAI), and Amikacin Liposome Inhalation Suspension (ALIS) may be used interchangeably throughout this study and other studies evaluating amikacin liposome inhalation suspension.

Eligibility criteria: Key Inclusion Criteria:

* Written informed consent or assent
* Subject has completed study TR02-108, and has been compliant with the study protocol
* Women of childbearing potential must agree to use reliable methods of contraception for the duration of the study

Key Exclusion Criteria:

* Subject met any of the listed criteria for study drug discontinuation in protocol TR02-108.
* Abnormal laboratory assessments including LFT (≥ 3× upper limit of normal \[ULN\]), serum creatinine (\> 2× ULN) and absolute neutrophil count \[ANC\] (\< 1000).
* Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.
* History of alcohol, medication or illicit drug abuse within the 6 months prior to consent.
* Smoking tobacco or any substance within 6 months prior to consent or anticipated inability to refrain from smoking throughout the study

Primary outcomes:
measure: Treatment Emergent Adverse Events (TEAEs) up to Day 672
timeFrame: From Study Initiation up to Day 672
measure: Laboratory Abnormalities up to Day 672
timeFrame: Baseline, Day 377 and Day 672
measure: Acute Tolerability as Measured by Pulmonary Function Test (PFT) Changes Pre to Post Dose
timeFrame: Day 1, Day 84, Day 196, Day 281, Day 337, Day 449, Day 532 and Day 644
measure: Respiratory Rate: Change From Baseline to Day 672
timeFrame: From Study Initiation up to Day 672
measure: Heart Rate: Change From Baseline From Day 672
timeFrame: From Study Initiation up to Day 672
measure: Systolic BP: Change From Baseline at Day 672
timeFrame: From Study Initiation up to Day 672
measure: Diastolic BP: Change From Baseline at Day 672
timeFrame: From Study Initiation up to Day 672
measure: Body Temperature: Change From Baseline at Day 672
timeFrame: From Study Initiation up to Day 672
measure: Oxygen Saturation: Change From Baseline at Day 672
timeFrame: From Study Initiation up to Day 672
measure: Minimum Inhibitory Concentrations (MICs) for Pseudomonas Aeruginosa (Pa) and Burkholderia Species From Day 1 to Days 169, 337, 505 and 672
timeFrame: Day 1, Day 169, Day 337, Day 505 and Day 672
measure: Evaluation of Audiology
timeFrame: Day 337 and Day 672
measure: Change in Serum Creatinine Throughout the Study
timeFrame: Baseline, Day 337 and Day 672
Secondary outcomes:
measure: Percent Change in FEV1 Throughout the Study
timeFrame: Baseline, Day 337 and Day 672
measure: Number of Subjects Experiencing a Protocol Defined Pulmonary Exacerbation
timeFrame: From Study Initiation up to Day 700
measure: Number of Subjects Initiating Treatment.
timeFrame: From Study Initiation up to Day 672
measure: Number of Participants Who Received Antipseudomonal Antibiotic Treatment for Protocol Defined Pulmonary Exacerbation
timeFrame: From Study Initiation up to Day 700
Other outcomes:
Locations:
city: Vienna
country: Austria
city: Antwerp
country: Belgium
city: Brussels
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Halifax
country: Canada
city: Hamilton
country: Canada
city: Vancouver
country: Canada
city: Copenhagen
country: Denmark
city: Lille
country: France
city: Paris
country: France
city: Berlin
country: Germany
city: Essen
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Munchen
country: Germany
city: Athens
country: Greece
city: Maroussi
country: Greece
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Szeged
country: Hungary
city: Dublin
country: Ireland
city: Brescia
country: Italy
city: Catania
country: Italy
city: Parma
country: Italy
city: Roma
country: Italy
city: Verona
country: Italy
city: Utrecht
country: Netherlands
city: Gdansk
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Rabka-Zdroj
country: Poland
city: Rzeszow
country: Poland
city: Warsaw
country: Poland
city: Belgrade
country: Serbia
city: Banská Bystrica
country: Slovakia
city: Bratislava
country: Slovakia
city: Kosice
country: Slovakia
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Penarth
country: United Kingdom
Study officials:
affiliation: Insmed Incorporated
name: Gina Eagle, MD
role: STUDY_DIRECTOR
References:
citation: Bilton D, Fajac I, Pressler T, Clancy JP, Sands D, Minic P, Cipolli M, Galeva I, Sole A, Quittner AL, Jumadilova Z, Ciesielska M, Konstan MW; CLEAR-110 Study Group. Long-term amikacin liposome inhalation suspension in cystic fibrosis patients with chronic P. aeruginosa infection. J Cyst Fibros. 2021 Nov;20(6):1010-1017. doi: 10.1016/j.jcf.2021.05.013. Epub 2021 Jun 16.