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

May 26, 2022 updated by: Gilead Sciences

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
149

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria, 8036
        • Medizinische Universitat Graz
      • Innsbruck, Austria, 06020
        • Medizinische Universitat Innsbruck
  • Belgium
      • Brussels, Belgium, 1020
        • Hôpital Universitaire des Enfants Reine Fabiola
      • Edegem, Belgium, 2650
        • UZ Antwerpen
  • Denmark
      • Aarhus N, Denmark, 8200
        • Aarhus University Hospital
      • Copenhagen, Denmark, 2100
        • Rigshospitalet
  • France
      • Bordeaux, France, 33076
        • Hopital des enfants - GH Pellegrin
      • Grenoble, France, 38043
        • Chu Grenoble Alpes
      • Paris, France, 75019
        • Hôpital Robert Debré APHP
  • Germany
      • Essen, Germany, 45147
        • Universitatsklinikum Essen
      • Kiel, Germany, 24116
        • Stadtisches Krankenhaus Kiel
  • Greece
      • Thessaloniki, Greece, 54642
        • General Hospital of Thessaloniki,3rd Dept of Pediatrics
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Corporation
      • Haifa, Israel, 3436212
        • Lady Davis Carmel Medical Center
      • Jerusalem, Israel, 9765422
        • Hadassah University Hospital Mount Scopus
      • Petah Tikva, Israel, 4920230
        • Schneider Children's Medical Center of Israel
  • Italy
      • Catania, Italy, 95123
        • Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
      • Milano, Italy, 20122
        • Fondazione IRCCS Cà Granda
      • Napoli, Italy, 80131
        • Azienda Ospedaliera Universitaria "Federico II"
      • Roma, Italy, 00165
        • Ospedale Pediatrico Bambino Gesu
      • Roma, Italy, 00161
        • Azienda Policlinico Umberto - Universita La Sapienza di Roma
      • Verona, Italy, 37126
        • Azienda Ospedaliera Universitaria Integrata Verona
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • VU University Medical Center
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall D hebron
      • Esplugues de Llobregat, Spain, 08950
        • Hospital Sant Joan de Déu
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Malaga, Spain, 29011
        • Hospital Regional Universitario de Malaga
      • Sabadell, Spain, 08208
        • Corporacio Sanitaria Parc Tauli
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario
  • United Kingdom
      • Aberdeen, United Kingdom, AB25 2ZG
        • NHS Grampian
      • Birmingham, United Kingdom, B4 6NH
        • Birmingham Children's Hospital NHS Foundation Trust
      • Exeter, United Kingdom, EX2 5DW
        • Royal Devon and Exeter Foundation NHS Trust
      • Leicester, United Kingdom, LE1 5WW
        • University Hospitals Of Leicester Nhs Trust
      • London, United Kingdom, SE5 9RS
        • Kings College Hospital NHS Foundation Trust
      • London, United Kingdom, E1 1BB
        • Barts and the London Children's Hospital
      • Manchester, United Kingdom, M13 9WL
        • Royal Manchester Children's Hospital
      • Middlesbrough, United Kingdom, TS4 3BW
        • South Tees Hospitals NHS Foundation Trust
      • Sheffield, United Kingdom, S10 2TH
        • Sheffield Children's Hospital NHS Trust
      • Southampton, United Kingdom, SO16 6YD
        • Southampton University Hospitals NHS Trust, Southampton General Hospital
      • Stoke on Trent, United Kingdom, ST4 6QG
        • University Hospitals of North Midlands NHS trust Royal Stoke University Hospital
  • United States
    • California
      • San Francisco, California, United States, 94158
        • University of California San Francisco (UCSF) - Benioff Children's Hospital
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Health System
    • Florida
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital Outpatient Care Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H Lurie Childrens Hospital of Chicago
      • Chicago, Illinois, United States, 60637
        • Corner Children's Hospital
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28277
        • Clinical Research of Charlotte
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • USC Department of Pediatrics/Division of Pediatric Pulmonology
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • Tyler, Texas, United States, 75708
        • The University of Texas Health Science Center at Tyler
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

3 months to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
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.
EXPERIMENTAL: AZLI
75 mg/ml of aztreonam will be administered TID for 28 days.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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)
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)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Last dose date of AZLI up to Week 112
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)
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).
Last dose date of AZLI up to Week 112

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 28, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 27, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 23, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 13, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 13, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 17, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 14, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 26, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GS-US-205-1850
  • 2016-002749-42 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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/

IPD Sharing Time Frame

18 months after study completion

IPD Sharing Access Criteria

A secured external environment with username, password, and RSA code.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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