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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03219164
Recruitment Status : Terminated (Study was terminated early by sponsor due to the challenges and risks introduced by Coronavirus disease 2019 (COVID-19) pandemic.)
First Posted : July 17, 2017
Results First Posted : May 16, 2022
Last Update Posted : June 14, 2022
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE July 13, 2017
First Posted Date  ICMJE July 17, 2017
Results First Submitted Date  ICMJE March 2, 2022
Results First Posted Date  ICMJE May 16, 2022
Last Update Posted Date June 14, 2022
Actual Study Start Date  ICMJE November 28, 2017
Actual Primary Completion Date May 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE Study of Aztreonam for Inhalation in Children With Cystic Fibrosis and New Infection of the Airways by Pseudomonas Aeruginosa Bacteria
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Pseudomonas Aeruginosa Respiratory Tract Infection/Colonization
  • Cystic Fibrosis
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 12, 2020)
149
Original Estimated Enrollment  ICMJE
 (submitted: July 13, 2017)
140
Actual Study Completion Date  ICMJE September 23, 2021
Actual Primary Completion Date May 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Months to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   Denmark,   France,   Germany,   Greece,   Israel,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03219164
Other Study ID Numbers  ICMJE 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  ICMJE
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  ICMJE Gilead Sciences
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP