Back to resultsStudy of Aztreonam for Inhalation in Children With Cystic Fibrosis and New Infection of the Airways by Pseudomonas Aeruginosa Bacteria (ALPINE 2)
Primary Purpose
Pseudomonas Aeruginosa Respiratory Tract Infection/Colonization, Cystic Fibrosis
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
AZLI
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pseudomonas Aeruginosa Respiratory Tract Infection/Colonization
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
Sites / Locations
- University of California San Francisco (UCSF) - Benioff Children's Hospital
- Children's National Health System
- Johns Hopkins All Children's Hospital Outpatient Care Center
- Ann & Robert H Lurie Childrens Hospital of Chicago
- Corner Children's Hospital
- University of Mississippi Medical center
- Clinical Research of Charlotte
- Cleveland Clinic
- USC Department of Pediatrics/Division of Pediatric Pulmonology
- Cook Children's Medical Center
- The University of Texas Health Science Center at Tyler
- University of Utah
- Medizinische Universitat Graz
- Medizinische Universitat Innsbruck
- Hopital Universitaire des Enfants Reine Fabiola
- UZ Antwerpen
- Aarhus University Hospital
- Rigshospitalet
- Hopital des enfants - GH Pellegrin
- CHU Grenoble Alpes
- Hopital Robert Debre APHP
- Universitatsklinikum Essen
- Stadtisches Krankenhaus Kiel
- General Hospital of Thessaloniki,3rd Dept of Pediatrics
- Rambam Health Corporation
- Lady Davis Carmel Medical Center
- Hadassah University Hospital Mount Scopus
- Schneider Children's Medical Center of Israel
- Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
- Fondazione IRCCS ca Granda
- Azienda Ospedaliera Universitaria "Federico II"
- Azienda Policlinico Umberto - Universita La Sapienza di Roma
- Ospedale Pediatrico Bambino Gesu
- Azienda Ospedaliera Universitaria Integrata Verona
- VU University Medical Center
- Hospital Universitario Vall d Hebron
- Hospital Sant Joan de Deu
- Hospital Universitario La Paz
- Hospital Regional Universitario de Malaga
- Corporacio Sanitaria Parc Tauli
- Hospital Universitario Virgen del Rocio
- Hospital Clinico Universitario
- NHS Grampian
- Birmingham Children's Hospital NHS Foundation Trust
- Royal Devon and Exeter Foundation NHS Trust
- University Hospitals of Leicester NHS trust
- Barts and the London Children's Hospital
- Kings College Hospital NHS foundation Trust
- Royal Manchester Children's Hospital
- South Tees Hospitals NHS Foundation Trust
- Sheffield Children's Hospital NHS Trust
- Southampton University Hospitals NHS trust, Southampton General Hospital
- University Hospitals of North Midlands NHS trust Royal Stoke University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
AZLI + Placebo
AZLI
Arm Description
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.
75 mg/ml of aztreonam will be administered TID for 28 days.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Time From Primary Eradication to PA Recurrence Over a 108-Week Post-Treatment Follow-up Period
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 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
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03219164
Brief Title
Study of Aztreonam for Inhalation in Children With Cystic Fibrosis and New Infection of the Airways by Pseudomonas Aeruginosa Bacteria
Acronym
ALPINE 2
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
Study was terminated early by sponsor due to the challenges and risks introduced by Coronavirus disease 2019 (COVID-19) pandemic.
Study Start Date
November 28, 2017 (Actual)
Primary Completion Date
May 27, 2020 (Actual)
Study Completion Date
September 23, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pseudomonas Aeruginosa Respiratory Tract Infection/Colonization, Cystic Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
149 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZLI + Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
AZLI
Arm Type
Experimental
Arm Description
75 mg/ml of aztreonam will be administered TID for 28 days.
Intervention Type
Drug
Intervention Name(s)
AZLI
Other Intervention Name(s)
Cayston®, Aztreonam
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
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)
Secondary Outcome Measure Information:
Title
Time From Primary Eradication to PA Recurrence Over a 108-Week Post-Treatment Follow-up Period
Description
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.
Time Frame
Last dose date of AZLI up to Week 112
Title
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)
Title
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
Description
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).
Time Frame
Last dose date of AZLI up to Week 112
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Francisco (UCSF) - Benioff Children's Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Children's National Health System
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Johns Hopkins All Children's Hospital Outpatient Care Center
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Ann & Robert H Lurie Childrens Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Corner Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Mississippi Medical center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Clinical Research of Charlotte
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28277
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
USC Department of Pediatrics/Division of Pediatric Pulmonology
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
The University of Texas Health Science Center at Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75708
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Medizinische Universitat Graz
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Medizinische Universitat Innsbruck
City
Innsbruck
ZIP/Postal Code
06020
Country
Austria
Facility Name
Hopital Universitaire des Enfants Reine Fabiola
City
Brussels
ZIP/Postal Code
1020
Country
Belgium
Facility Name
UZ Antwerpen
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Aarhus University Hospital
City
Aarhus N
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Hopital des enfants - GH Pellegrin
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
CHU Grenoble Alpes
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Hopital Robert Debre APHP
City
Paris
ZIP/Postal Code
75019
Country
France
Facility Name
Universitatsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Stadtisches Krankenhaus Kiel
City
Kiel
ZIP/Postal Code
24116
Country
Germany
Facility Name
General Hospital of Thessaloniki,3rd Dept of Pediatrics
City
Thessaloniki
ZIP/Postal Code
54642
Country
Greece
Facility Name
Rambam Health Corporation
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Lady Davis Carmel Medical Center
City
Haifa
ZIP/Postal Code
3436212
Country
Israel
Facility Name
Hadassah University Hospital Mount Scopus
City
Jerusalem
ZIP/Postal Code
9765422
Country
Israel
Facility Name
Schneider Children's Medical Center of Israel
City
Petah Tikva
ZIP/Postal Code
4920230
Country
Israel
Facility Name
Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
City
Catania
ZIP/Postal Code
95123
Country
Italy
Facility Name
Fondazione IRCCS ca Granda
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria "Federico II"
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Azienda Policlinico Umberto - Universita La Sapienza di Roma
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Ospedale Pediatrico Bambino Gesu
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Integrata Verona
City
Verona
ZIP/Postal Code
37126
Country
Italy
Facility Name
VU University Medical Center
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Hospital Universitario Vall d Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Sant Joan de Deu
City
Esplugues de Llobregat
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Regional Universitario de Malaga
City
Malaga
ZIP/Postal Code
29011
Country
Spain
Facility Name
Corporacio Sanitaria Parc Tauli
City
Sabadell
ZIP/Postal Code
08208
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Clinico Universitario
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
NHS Grampian
City
Aberdeen
ZIP/Postal Code
AB25 2ZG
Country
United Kingdom
Facility Name
Birmingham Children's Hospital NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Royal Devon and Exeter Foundation NHS Trust
City
Exeter
ZIP/Postal Code
EX2 5DW
Country
United Kingdom
Facility Name
University Hospitals of Leicester NHS trust
City
Leicester
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Facility Name
Barts and the London Children's Hospital
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Facility Name
Kings College Hospital NHS foundation Trust
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Royal Manchester Children's Hospital
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
South Tees Hospitals NHS Foundation Trust
City
Middlesbrough
ZIP/Postal Code
TS4 3BW
Country
United Kingdom
Facility Name
Sheffield Children's Hospital NHS Trust
City
Sheffield
ZIP/Postal Code
S10 2TH
Country
United Kingdom
Facility Name
Southampton University Hospitals NHS trust, Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
University Hospitals of North Midlands NHS trust Royal Stoke University Hospital
City
Stoke on Trent
ZIP/Postal Code
ST4 6QG
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.gileadclinicaltrials.com/transparency-policy/
Learn more about this trial
Study of Aztreonam for Inhalation in Children With Cystic Fibrosis and New Infection of the Airways by Pseudomonas Aeruginosa Bacteria
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