Safety and Efficacy of 2 Treatment Regimens of Aztreonam for Inhalation Solution in Children With Cystic Fibrosis and New Onset Pseudomonas Aeruginosa Infection (ALPINE2)

• ClinicalTrials.gov Identifier: NCT03219164
• Recruitment Status: Recruiting
• First Posted: July 17, 2017
• Last Update Posted: February 13, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: July 13, 2017
• First Posted Date: July 17, 2017
• Last Update Posted Date: February 13, 2020
• Actual Study Start Date: November 28, 2017
• Estimated Primary Completion Date: March 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 13, 2017): The Proportion of Participants with PA-Negative Cultures Through 28 Days Posttreatment in the14-Day Treatment Group vs the 28-day Treatment Group [ Time Frame: Up to 28 days Posttreatment ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03219164 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: July 13, 2017)

• Time from Primary Eradication to PA Recurrence over the 108-Week Posttreatment Follow-Up Period [ Time Frame: Up to Posttreatment Week 108 ]
  The primary eradication is achieved when all cultures at 14 and 28 days post AZLI treatment are PA negative.
• Proportion of Participants with PA-Negative Cultures Through 28 Days Posttreatment in the 14-day Treatment Group vs. Historical Pooled Data for PA Eradication at 28 days Posttreatment in Participants Treated with Tobramycin Nebulizer Solution (TNS) [ Time Frame: 28 days Posttreatment ]
  The historical data for the proportion of participants with PA-negative cultures during 28 days post-treatment period will be pooled from the published results from the studies conducted on the participants with new onset of PA infection and similar TNS treatment duration and follow-up.
• Time to PA Recurrence over the 108-week Posttreatment Follow-Up Period for a Sub-Group of Participants Matching the Population in the TNS ELITE Study Over a 108-week Posttreatment Follow-Up Period [ Time Frame: Up to Posttreatment Week 108 ]
  TNS Elite study is treatment of early Pseudomonas aeruginosa infection in participants with cystic fibrosis

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of 2 Treatment Regimens of Aztreonam for Inhalation Solution in Children With Cystic Fibrosis and New Onset Pseudomonas Aeruginosa Infection
• Official Title: Randomized, Double-Blind, Phase 3B Trial to Evaluate the Safety and Efficacy of 2 Treatment Regimens of Aztreonam 75 mg Powder and Solvent for Nebulizer Solution / Aztreonam for Inhalation Solution (AZLI) in Pediatric Subjects With Cystic Fibrosis (CF) and New Onset Respiratory Tract Pseudomonas Aeruginosa (PA) Infection/Colonization
• Brief Summary: The primary objective of this study is to evaluate the safety and efficacy of a 14-day course versus a 28-day course of aztreonam for inhalation solution (AZLI) in participants with new onset Pseudomonas aeruginosa respiratory tract infection.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Pseudomonas Aeruginosa Respiratory Tract Infection
• Cystic Fibrosis

Intervention

• Drug: AZLI
  75 mg/ml of aztreonam administered thrice daily via the PARI Altera® Nebulizer System. Participants < 2 years will receive via the SmartMask® Baby, 2 to < 6 years via the SmartMask Kids® and > 6 years via the nebulizer mouthpiece.
  Other Name: Cayston®
• Drug: Placebo
  Placebo administered thrice daily via the PARI Altera® Nebulizer System. Participants < 2 years will receive via the SmartMask® Baby, 2 to < 6 years via the SmartMask Kids® and > 6 years via the nebulizer mouthpiece.

Study Arms

• Experimental: AZLI
  AZLI for 28 days
  Intervention: Drug: AZLI
• Experimental: AZLI + Placebo
  AZLI for 14 days followed by placebo for 14 days
  Interventions:

  • Drug: AZLI
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 13, 2017): 140
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2021
• Estimated Primary Completion Date: March 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Diagnosis of Cystic Fibrosis (CF) as determined by the 2008 CF Consensus Conference criteria: Sweat chloride level ≥ 60 milliequivalents per liter (mEq/L) by quantitative pilocarpine iontophoresis; or a genotype with 2 identifiable mutations consistent with CF; or an abnormal nasal transepithelial potential difference (NPD), and 1 or more clinical features consistent with CF
• Documented new onset of positive respiratory tract culture for PA within 30 days of screening defined as either first lifetime documented PA-positive culture, or PA recovered after at least a 2-year history of PA-negative respiratory cultures (at least 2 cultures per year)
• Forced expiratory volume in one second (FEV1) ≥ 80% predicted (for subjects ≥ 6 years of age who can reliably perform spirometry assessments)
• Clinically stable with no evidence of acute significant respiratory symptoms that would require administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization

Key Exclusion Criteria:

• Use of IV or inhaled antipseudomonal antibiotics within 2 years of screening
• Use of oral antipseudomonal antibiotics for a respiratory event within 30 days of study entry (screening visit)
• History of intolerance to inhaled short acting β2 agonists
• History of lung transplantation
• Current requirement for daily continuous oxygen supplementation or requirement of more than 2 L/minute at night
• Hospitalization for a respiratory event within 30 days prior to screening
• Changes in bronchodilator, corticosteroid, dornase alfa, or hypertonic saline medications within 7 days prior to screening.
• Significant changes (per investigators discretion) in physiotherapy technique or schedule within 7 days prior to screening
• Abnormal renal or hepatic function results at most recent test within the previous 12 months, defined as Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper limit of normal (ULN), or Serum creatinine > 2 times ULN for age
• Presence of a condition or abnormality that would compromise the subject's safety or the quality of the study data, in the opinion of the Investigator
• Known hypersensitivity to aztreonam, its metabolites, or formulation excipients in AZLI
• Respiratory cultures performed within 24 months prior to screening that are positive for ANY Burkholderia spp. or Non-tuberculous Mycobacteria (NTM)

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Months to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Gilead Clinical Study Information Center; 1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

• Listed Location Countries: Austria, Belgium, Denmark, France, Germany, Greece, Israel, Italy, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03219164
• Other Study ID Numbers: GS-US-205-1850; 2016-002749-42 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: February 2020