Study of Aztreonam for Inhalation in Children With Cystic Fibrosis and New Infection of the Airways by Pseudomonas Aeruginosa Bacteria (ALPINE 2)

• ClinicalTrials.gov Identifier: NCT03219164
• Recruitment Status: Terminated
• First Posted: July 17, 2017
• Results First Posted: May 16, 2022
• Last Update Posted: June 14, 2022
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: July 13, 2017
• First Posted Date: July 17, 2017
• Results First Submitted Date: March 2, 2022
• Results First Posted Date: May 16, 2022
• Last Update Posted Date: June 14, 2022
• Actual Study Start Date: November 28, 2017
• Actual Primary Completion Date: May 27, 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 2, 2022): Percentage of Participants With Pseudomonas Aeruginosa (PA)-Negative Cultures Through 28 Days Post-Treatment in the 14-Day Treatment Group vs 28-Day Treatment Group [ Time Frame: 28 days post treatment (Weeks 4 to 6 for the 14 Day treatment group and Weeks 4 to 8 for the 28 Day treatment group) ]
• Original 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 ]

Current Secondary Outcome Measures (submitted: April 22, 2022)

• Time From Primary Eradication to PA Recurrence Over a 108-Week Post-Treatment Follow-up Period [ Time Frame: Last dose date of AZLI up to Week 112 ]
  The primary eradication was achieved when all cultures through 28 days post AZLI treatment were PA negative. Recurrence after PA eradication was defined as first positive PA culture result in participant who successfully met primary endpoint and had no PA-positive culture from local lab at Week 4 through Week 6 for AZLI 14 Days group or through Week 8 for AZLI 28 Days group.
• Percentage of Participants With PA-negative Cultures Through 28 Days Post-Treatment in the 14-Day Treatment Group vs Historical Pooled Data for PA Eradication at 28 Days Post-Treatment in Participants Treated With Tobramycin Nebulizer Solution (TNS) [ Time Frame: 28 days post treatment (Weeks 4 to 6 for the 14 Day treatment group) ]
• Time to PA Recurrence for a Sub-Group of Participants Matching the Population in the TNS ELITE Study Over a 108-Week Post-Treatment Follow-up Period [ Time Frame: Last dose date of AZLI up to Week 112 ]
  In ELITE study (NCT00391976), participants with cystic fibrosis who had early PA infection received TNS. Published criteria for efficacy analysis population in ELITE study included:

  • Participants must be ≥ 6 months at randomization
  • No history of positive anti-PA antibody (no anti-PA immunoglobulin G [IgG] antibody interpretation at Screening/Baseline) on record
  • Did not use anti-pseudomonal antibiotics through 28 days after completion of active treatment and within 2 years of Screening
  • Non-missing PA culture result at 28 days after last dose of AZLI
  • PA negative through 28 days after completion of active treatment
  • No important protocol deviation related to compliance with study drug administration
  • 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).

Original 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Aztreonam for Inhalation in Children With Cystic Fibrosis and New Infection of the Airways by Pseudomonas Aeruginosa Bacteria
• 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 pediatric participants with new onset Pseudomonas aeruginosa respiratory tract infection or colonization.
• 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/Colonization
• Cystic Fibrosis

Intervention

• Drug: AZLI
  Administered 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 Names:

  • Cayston®
  • Aztreonam
• Drug: Placebo
  Administered 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 + Placebo
  75 mg/ml of aztreonam will be administered thrice daily (TID) for 14 days followed by placebo to match (PTM) aztreonam TID for 14 days.
  Interventions:

  • Drug: AZLI
  • Drug: Placebo
• Experimental: AZLI
  75 mg/ml of aztreonam will be administered TID for 28 days.
  Intervention: Drug: AZLI

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 12, 2020): 149
• Original Estimated Enrollment (submitted: July 13, 2017): 140
• Actual Study Completion Date: September 23, 2021
• Actual Primary Completion Date: May 27, 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 intravenous (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 information is only displayed when the study is recruiting subjects
• 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

• Plan to Share IPD: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy/
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: https://www.gileadclinicaltrials.com/transparency-policy/

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: May 2022