Clinical trial NCT01315678: Study to Evaluate Arikayce™ in CF Patients With Chronic Pseudomonas Aeruginosa Infections
Official title: Randomized, Open-Label, Active-Controlled, Multicenter Study to Assess the Efficacy, Safety and Tolerability of Arikayce™ in Cystic Fibrosis Patients With Chronic Infection Due to Pseudomonas Aeruginosa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pseudomonas Aeruginosa Infection
Keywords: Cystic Fibrosis
Respiratory Infections
Pulmonary Cystic Fibrosis
CFTR
Amikacin
Anti-bacterial Agents
Amikacin liposome inhalation suspension (ALIS)
Lead sponsor: Insmed Incorporated
Sponsor class: INDUSTRY
First posted: 2011-03-15
Enrollment: 302
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A major factor in the respiratory health of Cystic Fibrosis (CF) participants is the prevalence of chronic Pseudomonas aeruginosa (Pa) infections. The Pa infection rate in CF patients increases with age and by age 18 years approximately 85% of CF patients in the US are infected. Liposomal amikacin for inhalation (Arikayce™) was developed as a possible treatment for chronic infection due to Pa in CF patients.

The purpose of this study is to determine whether Arikayce™ is effective in treating chronic lung infections caused by Pa in CF participants. The effectiveness, safety, and tolerability of Arikayce™ will be compared to Tobramycin TOBI®, an inhalation antibiotic already available for use.

Detailed description: CF is a genetic disease resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Patients with CF manifest pathological changes in a variety of organs that express CFTR. The lungs are frequently affected often resulting in chronic infections by bacteria such as Pseudomonas aeruginosa and airway inflammation. Treatment of chronic lung infections is one of the principal goals of CF therapy. Arikayce™ LAI (liposomal amikacin for inhalation) is a sustained-release formulation of amikacin encapsulated inside nanoscale liposomal carriers designed for administration via inhalation. It is hypothesized that the sustained-release pulmonary targeting and biofilm penetration properties of this formulation will have several advantages over current therapies in treating CF patients with chronic lung infection caused by Pseudomonas aeruginosa.

This Phase 3 study has been designed to evaluate the efficacy, safety and tolerability of Arikayce™ in treating CF patients with chronic bronchopulmonary infection compared to a currently available antibiotic, TOBI® Inhalation Solution. Eligible participants will be randomized 1:1 to receive 590 mg of Arikayce™ once daily via a PARI Investigational eFlow® Nebulizer or 300 mg TOBI® BID via a PARI LC® PLUS nebulizer. Participants will receive 3 cycles of treatment with each cycle being comprised of 28 days on treatment followed by 28 days off-treatment. Total study duration is up to 186 days (\~6 months) including an up to 18 day Screening period. Participants will be evaluated for safety, tolerability and efficacy bi-weekly during the first 4 weeks of treatment, and thereafter every 4 weeks for the duration of the study. Pharmacokinetics (PK) of Arikayce™ in blood, sputum and 24-hour urine will be determined in a subgroup of study participants who consent to PK evaluation.

At the completion of the TR02-108 protocol, participants who have consented and meet study safety criteria may enroll in the long-term, open-label, multi-cycle extension study of 590 mg of Arikayce™ (under a separate protocol TR02-110). 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
* Confirmed diagnosis of CF
* History of chronic infection with Pseudomonas aeruginosa
* Sputum culture positive for Pseudomonas aeruginosa at Screening
* FEV1 ≥ 25% of predicted value at Screening

Key Exclusion Criteria:

* FEV1 \<25% of predicted at Screening
* History of major complications of lung disease within 8 weeks prior to Screening
* Hemoptysis of ≥60 mL in a 24-hour period within 4 weeks prior to Screening
* History of positive culture for Burkholderia cepacia within 2 years prior to Screening
* History of pulmonary tuberculosis or non-tuberculous mycobacterial lung disease treated within 2 years prior to Screening or requiring treatment at the time of screening
* History of Allergic Broncho-Pulmonary Aspergillosis or any other condition requiring systemic steroids at a dose ≥ equivalent of 10 mg/day of prednisone within 3 months prior to Screening
* Presence of any clinically significant cardiac disease
* History of lung transplantation
* Daily, continuous oxygen supplementation or nighttime supplemental oxygen requirement of greater than 2 L/min
* Administration of any investigational products within 8 weeks prior to study Day 1
* Smoking tobacco or any substance within 6 months prior to screening or anticipated inability to refrain from smoking throughout the study

Primary outcomes:
measure: Pulmonary Function Test: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline to168 days
Secondary outcomes:
measure: Pumonary Function Test: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline, Day 14, Day 28, Day 57, Day 84, Day 113, Day 140 and Day 168.
measure: Number of Participants Experiencing a Pulmonary Exacerbation
timeFrame: 168 days
measure: Number of Participants to First Antipseudomonal Antibiotic Treatment for Pulmonary Exacerbation
timeFrame: 168 days
measure: Number of Participants to First All Cause Hospitalization
timeFrame: 168 days
measure: Change in Density (Log CFU) in Pseudomonas Aeruginosa in Sputum
timeFrame: Baseline, Day 14, Day 28, Day 57, Day 84, Day 113, Day 140 and Day 168
measure: Relative Percent (%) Change in Respiratory Symptoms as Measured by the CFQ-R
timeFrame: Day 14, Day 28, Day 57, Day 84, Day 113, Day 140 and Day 168
Other outcomes:
Locations:
city: Vienna
country: Austria
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: Hamilton
country: Canada
state: Ontario
city: Halifax
country: Canada
city: Vancouver
country: Canada
city: Copenhagen
country: Denmark
city: Bron
country: France
city: Lille
country: France
city: Montpellier
country: France
city: Nancy
country: France
city: Paris
country: France
city: Pierre Benite
country: France
city: Rouen
country: France
city: Berlin
country: Germany
city: Essen
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Kiel
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: Ancona
country: Italy
city: Brescia
country: Italy
city: Catania
country: Italy
city: Genova
country: Italy
city: Milan
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: New Belgrade
country: Serbia
city: Banska Bystrica
country: Slovakia
city: Bratislava
country: Slovakia
city: Kosice
country: Slovakia
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Goteborg
country: Sweden
city: Birmingham
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Leeds
country: United Kingdom
city: Liverpool
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, Pressler T, Fajac I, Clancy JP, Sands D, Minic P, Cipolli M, Galeva I, Sole A, Quittner AL, Liu K, McGinnis JP 2nd, Eagle G, Gupta R, Konstan MW; CLEAR-108 Study Group. Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis. J Cyst Fibros. 2020 Mar;19(2):284-291. doi: 10.1016/j.jcf.2019.08.001. Epub 2019 Aug 23.