Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKAYCE™) - Extension Phase

NCT03905642 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: TR02-105 Extension
• Study Type: interventional
• Target: 49
• Locations: 7 countries
• Sites: 11

Brief Summary

A major factor in the respiratory health of cystic fibrosis (CF) patients is acquisition of chronic Pseudomonas (P.) aeruginosa infections. The infection rate with P. aeruginosa increases with age and by age 18 years, 80% of patients with CF in the U.S. are infected. Liposomal amikacin for inhalation (LAI; Arikayce™) is a sterile aqueous liposomal suspension consisting of amikacin sulfate encapsulated in liposomes. This formulation of amikacin maximizes the achievable dose and delivery to the lungs of infected patients when delivered via a nebulizer. Because liposome particles are small enough to penetrate and diffuse through sputum into the bacterial biofilm, they deposit drug close to the bacterial colonies (Meers, et al., 2008) (Clancy, et al., 2013), thus improving the bioavailability of amikacin at the infection site. The clinically achievable doses of amikacin in the LAI formulation can effectively increase the half-life of the drug in the lungs, and decrease the potential for systemic toxicity. LAI offers several advantages over current therapies in treating patients with CF with chronic infection caused by P. aeruginosa.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Respiratory Infections; Pulmonary Cystic Fibrosis; CFTR

Outcome Measures

Primary Outcomes (1)

• Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.

  Number of Participants with indicated Adverse Events in subjects receiving 560 mg once daily dose of Arikayce™ administered for 6 cycles over 18 months.

  18 Months

Secondary Outcomes (5)

• FEV1 % Predicted

  Baseline, Days1, 14, 28, 56, 70, 85, 98, 112, 140, 154, 169, 182,196, 224, 238, 253, 266, 280, 308, 322, 337, 350, 364, 392, 406, 421, 434, 448, 476, 490, and 504

• Absolute Change in Sputum Density

  Baseline, Days 14, 28, 85, 98, 112, 140, 169, 182,196, 253, 266, 280, 337, 350, 364, 421, 434, and 448

• Antipseudomonal Rescue Therapy - Duration of Therapy

  18 Months

• Antipseudomonal Rescue Therapy - Time to Therapy

  18 Months

• Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score

  Days 14, 28, 85, 98, 112, 169, 182,196, 253, 266, 280, 337, 350, 364, 421, 434, and 448

Study Arms (1)

560 mg Arikayce™

EXPERIMENTAL

Subjects in this cohort will receive 560 mg of Arikayce™

Drug: Arikayce™

Interventions

Arikayce™ DRUG

Amikacin (aminoglycoside) in a liposomal formulation.

Also known as: Liposomal amikacin inhalation, LAI

560 mg Arikayce™

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from the patient or designated legal guardian prior to the performance of any study related procedures.
• Male or female study subjects ≥ 6 years of age or older.
• Confirmed diagnosis of CF defined as a positive sweat chloride \> 60 milliequivalents (mEq)/liter (by pilocarpine iontophoresis) and/or a genotype with 2 identifiable mutations consistent with CF accompanied by one or more clinical features of the CF phenotype.
• History of chronic infection with P. aeruginosa (defined as 3 documented positive cultures in the prior 2 years of which at least one was obtained in the 3 months prior to randomization). The cultures could be obtained from the following respiratory secretions: sputum, throat swabs, nasopharyngeal swabs, or broncho-alveolar lavage fluid specimens.
• Study subjects must produce a screening specimen (expectorated or induced sputum, throat swabs, nasopharyngeal swabs, or broncho-alveolar lavage fluid) that is positive for growth of P. aeruginosa.
• FEV1 ≥ 40% of predicted at Screening.
• SaO2 ≥ 90% at Screening while breathing room air.
• Ability to comply with study medication use, study visits, and study procedures as judged by the investigator.
• Ability to produce 0.5 grams sputum or be willing to undergo an induction to produce sputum for clinical evaluation.
• Clinically stable with no evidence of acute upper or lower respiratory tract infection or history of pulmonary exacerbation within the 4 weeks prior to Screening.
• Written informed consent obtained from the patient or designated legal guardian prior to the performance of any study-related procedures in the extension period.

You may not qualify if:

• Administration of any investigational drug within 8 weeks prior to Screening.
• Emergency room visit or hospitalization for CF or respiratory-related illness within the 4 weeks prior to Screening.
• History of alcohol, medication, or illicit drug abuse within the 1 year prior to Screening.
• History of lung transplantation.
• Female of childbearing potential who is lactating or is not practicing an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD).
• Positive pregnancy test. All women of childbearing potential will be tested.
• Use of any anti-pseudomonal antibiotics (IV antibiotics, all inhalation antibiotics, oral fluoroquinolones) within the 28 days prior to Screening.
• Initiation of chronic therapy (i.e. TOBI®, high-dose ibuprofen, rhDNase, macrolide antibiotics) within the 28 days prior to Screening.
• History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of Screening.
• History of mycobacterial and/or Aspergillus infection requiring treatment within 2 years prior to Screening, and/or history of allergic bronchopulmonary aspergillosis (ABPA).
• History of biliary cirrhosis with portal hypertension, or splenomegaly (refer to study manual).
• GGT, AST, or ALT ≥ 3 times the upper limit of normal at Screening visit.
• ANC ≤ 1000 performed at Screening visit.
• Serum creatinine \> 1.5 times normal performed at Screening visit.
• History of daily, continuous oxygen supplementation or requirement for more than 2 L/min at night.

Sponsors & Collaborators

• Insmed Incorporated: lead

Study Sites (11)

Unknown Facility

Leuven, Belgium

Location

Unknown Facility

Budapest, Hungary

Location

Unknown Facility

Kaposvár, Hungary

Location

Unknown Facility

Skopje, North Macedonia

Location

Unknown Facility

Rabka-Zdrój, Poland

Location

Unknown Facility

Warsaw, Poland

Location

Unknown Facility

Belgrade, Serbia

Location

Unknown Facility

Bratislava, Slovakia

Location

Unknown Facility

Košice, Slovakia

Location

Unknown Facility

Kharkiv, Ukraine

Location

Unknown Facility

Kiev, Ukraine

Location

Related Publications (1)

• Clancy JP, Dupont L, Konstan MW, Billings J, Fustik S, Goss CH, Lymp J, Minic P, Quittner AL, Rubenstein RC, Young KR, Saiman L, Burns JL, Govan JR, Ramsey B, Gupta R; Arikace Study Group. Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax. 2013 Sep;68(9):818-25. doi: 10.1136/thoraxjnl-2012-202230. Epub 2013 Jun 8.

  PMID: 23749840 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis; Respiratory Tract Infections

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Infections

Results Point of Contact

• Title: Kevin Mange (Senior VP, Clinical Development and Medical Affairs)
• Organization: Insmed Incorporated

kevin.mange@insmed.com

908-947-2651

Study Officials

• Gina Eagle, MD

  Insmed Incorporated

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Extension phase for evaluation of safety, tolerability and efficacy. Single dose group of 560 mg of Arikase TM

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: April 5, 2019
• Study Start: January 8, 2009
• Primary Completion: November 2, 2010
• Study Completion: November 2, 2010
• Last Updated: July 30, 2020
• Results First Posted: May 14, 2019

Record last verified: 2020-07

Locations

SE (1); SL (2); UA (2); BE (1); PL (2); NO (1); HU (2)