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

NCT ID: NCT01315678

Last Updated: 2020-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 302 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2013-09-18

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.

Conditions

Pseudomonas Aeruginosa Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arikayce™

Arikayce™ is liposomal amikacin for inhalation

Group Type: EXPERIMENTAL

Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer.

Intervention Type: DRUG

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.

TOBI®

TOBI® is tobramycin inhalation solution

Group Type: ACTIVE_COMPARATOR

Tobramycin inhalation solution using a PARI LC® Plus nebulizer.

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insmed Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gina Eagle, MD

Role: STUDY_DIRECTOR

Insmed Incorporated

Locations

Vienna, , Austria

Brussels, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Pleven, , Bulgaria

Plovdiv, , Bulgaria

Sofia, , Bulgaria

Varna, , Bulgaria

Hamilton, Ontario, Canada

Halifax, , Canada

Vancouver, , Canada

Copenhagen, , Denmark

Bron, , France

Lille, , France

Montpellier, , France

Nancy, , France

Paris, , France

Pierre-Bénite, , France

Rouen, , France

Berlin, , Germany

Essen, , Germany

Hamburg, , Germany

Hanover, , Germany

Kiel, , Germany

München, , Germany

Athens, , Greece

Marousi, , Greece

Budapest, , Hungary

Debrecen, , Hungary

Szeged, , Hungary

Dublin, , Ireland

Ancona, , Italy

Brescia, , Italy

Catania, , Italy

Genova, , Italy

Milan, , Italy

Parma, , Italy

Roma, , Italy

Verona, , Italy

Utrecht, , Netherlands

Gdansk, , Poland

Lodz, , Poland

Lublin, , Poland

Poznan, , Poland

Rabka-Zdrój, , Poland

Rzeszów, , Poland

Warsaw, , Poland

New Belgrade, , Serbia

Banská Bystrica, , Slovakia

Bratislava, , Slovakia

Košice, , Slovakia

Barcelona, , Spain

Madrid, , Spain

Valencia, , Spain

Gothenburg, , Sweden

Birmingham, , United Kingdom

Glasgow, , United Kingdom

Leeds, , United Kingdom

Liverpool, , United Kingdom

London, , United Kingdom

Nottingham, , United Kingdom

Penarth, , United Kingdom

Countries

Austria; Belgium; Bulgaria; Canada; Denmark; France; Germany; Greece; Hungary; Ireland; Italy; Netherlands; Poland; Serbia; Slovakia; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 31451351 (View on PubMed)

Other Identifiers

TR02-108

Identifier Type: -

Identifier Source: org_study_id