Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate Arikayce™ in CF Patients With Chronic Pseudomonas Aeruginosa Infections

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01315678
Recruitment Status : Completed
First Posted : March 15, 2011
Results First Posted : June 24, 2019
Last Update Posted : June 24, 2019
Sponsor:
Information provided by (Responsible Party):
Insmed Incorporated

Tracking Information
First Submitted Date  ICMJE March 14, 2011
First Posted Date  ICMJE March 15, 2011
Results First Submitted Date  ICMJE April 3, 2019
Results First Posted Date  ICMJE June 24, 2019
Last Update Posted Date June 24, 2019
Actual Study Start Date  ICMJE February 29, 2012
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
Pulmonary Function Test: Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline to168 days ]
Relative Change (%) from baseline to end of study (Day 168) in FEV1 (1 second)
Original Primary Outcome Measures  ICMJE
 (submitted: March 14, 2011)
Relative change in Forced Expiratory Volume in 1 second (FEV1) from baseline to end of study (Day 168) [ Time Frame: 168 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
  • Pumonary Function Test: Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline, Day 14, Day 28, Day 57, Day 84, Day 113, Day 140 and Day 168. ]
    Relative changes (%) from baseline to Study Days 14, 28, 57, 84, 113, 140, 168 in FEV1
  • Number of Subjects Experiencing a Pulmonary Exacerbation [ Time Frame: 168 days ]
    Number of Subjects experiencing a pulmonary exacerbation measured by number with event and number censored
  • Number of Subjects to First Antipseudomonal Antibiotic Treatment for Pulmonary Exacerbation [ Time Frame: 168 days ]
    Number of Subjects to first antipseudomonal antibiotic treatment for pulmonary exacerbation measured by number with event and number censored
  • Number of Subjects to First All Cause Hospitalization [ Time Frame: 168 days ]
    Number of Subjects to first all cause hospitalization measured by number with event and number censored
  • Change in Density (Log CFU) in Pseudomonas Aeruginosa in Sputum [ Time Frame: Baseline, Day 14, Day 28, Day 57, Day 84, Day 113, Day 140 and Day 168 ]
    Change in density (Log CFU) from baseline in Pseudomonas aeruginosa in sputum
  • Relative Percent (%) Change in Respiratory Symptoms as Measured by the CFQ-R [ Time Frame: Day 14, Day 28, Day 57, Day 84, Day 113, Day 140 and Day 168 ]
    Quality of Life was measured by the absolute change from baseline in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory scale. Disease specific instrument designed to measure impact on overall health, daily life, perceived well-being and symptoms in patients with a diagnosis of cystic fibrosis. Scores range from 0 to 100, with higher scores indicating better health. Scores for each Health Related Quality of Life (HRQoL) domain; after recoding, each item is summed to generate a domain score and standardized.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2011)
  • Changes in pulmonary function throughout the study [ Time Frame: 168 days ]
  • Time to and proportion of subjects experiencing a pulmonary exacerbation [ Time Frame: 168 days ]
  • Time to first antipseudomonal antibiotic treatment for pulmonary exacerbation [ Time Frame: 168 days ]
  • Time to and number of hospitalizations [ Time Frame: 168 days ]
  • Change in density in Pseudomonas aeruginosa in sputum [ Time Frame: 168 days ]
  • Change in patient reported outcomes/symptoms [ Time Frame: 168 days ]
  • Evaluation of safety and tolerability [ Time Frame: 168 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate Arikayce™ in CF Patients With Chronic Pseudomonas Aeruginosa Infections
Official Title  ICMJE 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
Brief Summary

A major factor in the respiratory health of Cystic Fibrosis (CF) subjects 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 subjects. 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 subjects 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. Subjects 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. Subjects 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 subjects who consent to PK evaluation.

At the completion of the TR02-108 protocol, subjects 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pseudomonas Aeruginosa Infection
Intervention  ICMJE
  • Drug: Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer.

    Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

    • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
    • Administration time is approximately 13 minutes.
    • liposomal amikacin for inhalation will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
  • Drug: Tobramycin inhalation solution using a PARI LC® Plus nebulizer.

    300 mg tobramycin inhalation solution is administered twice a day using a PARI LC® Plus nebulizer.

    • Nebulization time is approximately 20 minutes for each administration.
    • Tobramycin inhalation solution will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment
Study Arms  ICMJE
  • Experimental: Arikayce™
    Arikayce™ is liposomal amikacin for inhalation
    Intervention: Drug: Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer.
  • Active Comparator: TOBI®
    TOBI® is tobramycin inhalation solution
    Intervention: Drug: Tobramycin inhalation solution using a PARI LC® Plus nebulizer.
Publications * Bilton D, Pressler T, Fajac I, Clancy JP, Sands D, Minic P, Cipolli M, Galeva I, Solé 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. 2019 Aug 23. pii: S1569-1993(19)30833-1. doi: 10.1016/j.jcf.2019.08.001. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 4, 2014)
302
Original Estimated Enrollment  ICMJE
 (submitted: March 14, 2011)
300
Actual Study Completion Date  ICMJE September 18, 2013
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   Bulgaria,   Canada,   Denmark,   France,   Germany,   Greece,   Hungary,   Ireland,   Italy,   Netherlands,   Poland,   Serbia,   Slovakia,   Spain,   Sweden,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01315678
Other Study ID Numbers  ICMJE TR02-108
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Insmed Incorporated
Study Sponsor  ICMJE Insmed Incorporated
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gina Eagle, MD Insmed Incorporated
PRS Account Insmed Incorporated
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP