Extension Study of Liposomal Amikacin for Inhalation in Cystic Fibrosis (CF) Patients With Chronic Pseudomonas Aeruginosa (Pa) Infection

NCT ID: NCT01316276

Last Updated: 2020-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-05
• Study Completion Date: 2015-07-16

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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LAI

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, divided into 2 periods of 6 cycles each (approximately 12 months each).

Group Type: EXPERIMENTAL

Liposomal amikacin for inhalation

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 in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.

Interventions

Liposomal amikacin for inhalation

• 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 in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. 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
• 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

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

• 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

Antwerp, , Belgium

Brussels, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Pleven, , Bulgaria

Plovdiv, , Bulgaria

Sofia, , Bulgaria

Varna, , Bulgaria

Halifax, , Canada

Hamilton, , Canada

Vancouver, , Canada

Copenhagen, , Denmark

Lille, , France

Paris, , France

Berlin, , Germany

Essen, , Germany

Hamburg, , Germany

Hanover, , Germany

München, , Germany

Athens, , Greece

Marousi, , Greece

Budapest, , Hungary

Debrecen, , Hungary

Szeged, , Hungary

Dublin, , Ireland

Brescia, , Italy

Catania, , Italy

Parma, , Italy

Roma, , Italy

Verona, , Italy

Utrecht, , Netherlands

Gdansk, , Poland

Lodz, , Poland

Lublin, , Poland

Poznan, , Poland

Rabka-Zdrój, , Poland

Rzeszów, , Poland

Warsaw, , Poland

Belgrade, , Serbia

Banská Bystrica, , Slovakia

Bratislava, , Slovakia

Košice, , Slovakia

Barcelona, , Spain

Madrid, , Spain

Valencia, , Spain

Leeds, , 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; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34144923 (View on PubMed)

Other Identifiers

TR02-110

Identifier Type: -

Identifier Source: org_study_id