Pseudomonas Aeruginosa Respiratory Tract Infection/ColonizationPhase 3ALPINE 2NCT03219164
Study of Aztreonam for Inhalation in Children With Cystic Fibrosis and New Infection of the Airways by Pseudomonas Aeruginosa Bacteria
A Phase 3 study testing AZLI in people with Pseudomonas Aeruginosa Respiratory Tract Infection/Colonization and Cystic Fibrosis, run by Gilead Sciences at 53 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 months to 18 years
- Conditions the study is for
- Pseudomonas Aeruginosa Respiratory Tract Infection/Colonization, Cystic Fibrosis
- What is being tested?
- AZLI
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 149 participants
- Where
- 53 sitesin 12 countries
- Study dates
- 28 Nov 2017to 23 Sep 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
53 sites in 12 countries.
53 sites in 12 countries
United States12 sites
Clinical Research of Charlotte
Charlotte, North Carolina, 28277
Ann & Robert H Lurie Childrens Hospital of Chicago
Chicago, Illinois, 60611
Corner Children's Hospital
Chicago, Illinois, 60637
Cleveland Clinic
Cleveland, Ohio, 44195
USC Department of Pediatrics/Division of Pediatric Pulmonology
Columbia, South Carolina, 29203
Cook Children's Medical Center
Fort Worth, Texas, 76104
University of Mississippi Medical center
Jackson, Mississippi, 39216
University of Utah
Salt Lake City, Utah, 84132
University of California San Francisco (UCSF) - Benioff Children's Hospital
San Francisco, California, 94158
Johns Hopkins All Children's Hospital Outpatient Care Center
St. Petersburg, Florida, 33701
The University of Texas Health Science Center at Tyler
Tyler, Texas, 75708
Children's National Health System
Washington D.C., District of Columbia, 20010
United Kingdom11 sites
NHS Grampian
Aberdeen, AB25 2ZG
Birmingham Children's Hospital NHS Foundation Trust
Birmingham, B4 6NH
Royal Devon and Exeter Foundation NHS Trust
Exeter, EX2 5DW
University Hospitals of Leicester NHS trust
Leicester, LE1 5WW
Barts and the London Children's Hospital
London, E1 1BB
Kings College Hospital NHS foundation Trust
London, SE5 9RS
Royal Manchester Children's Hospital
Manchester, M13 9WL
South Tees Hospitals NHS Foundation Trust
Middlesbrough, TS4 3BW
Sheffield Children's Hospital NHS Trust
Sheffield, S10 2TH
Southampton University Hospitals NHS trust, Southampton General Hospital
Southampton, SO16 6YD
University Hospitals of North Midlands NHS trust Royal Stoke University Hospital
Stoke-on-Trent, ST4 6QG
Spain7 sites
Hospital Universitario Vall d Hebron
Barcelona, 08035
Hospital Sant Joan de Deu
Esplugues de Llobregat, 08950
Hospital Universitario La Paz
Madrid, 28046
Hospital Regional Universitario de Malaga
Málaga, 29011
Corporacio Sanitaria Parc Tauli
Sabadell, 08208
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Clinico Universitario
Valencia, 46010
Italy6 sites
Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
Catania, 95123
Fondazione IRCCS ca Granda
Milan, 20122
Azienda Ospedaliera Universitaria "Federico II"
Naples, 80131
Azienda Policlinico Umberto - Universita La Sapienza di Roma
Roma, 00161
Ospedale Pediatrico Bambino Gesu
Roma, 00165
Azienda Ospedaliera Universitaria Integrata Verona
Verona, 37126
Israel4 sites
Rambam Health Corporation
Haifa, 3109601
Lady Davis Carmel Medical Center
Haifa, 3436212
Hadassah University Hospital Mount Scopus
Jerusalem, 9765422
Schneider Children's Medical Center of Israel
Petah Tikva, 4920230
France3 sites
Hopital des enfants - GH Pellegrin
Bordeaux, 33076
CHU Grenoble Alpes
Grenoble, 38043
Hopital Robert Debre APHP
Paris, 75019
Austria2 sites
Medizinische Universitat Graz
Graz, 8036
Medizinische Universitat Innsbruck
Innsbruck, 06020
Belgium2 sites
Hopital Universitaire des Enfants Reine Fabiola
Brussels, 1020
UZ Antwerpen
Edegem, 2650
Denmark2 sites
Aarhus University Hospital
Aarhus N, 8200
Rigshospitalet
Copenhagen, 2100
Germany2 sites
Universitatsklinikum Essen
Essen, 45147
Stadtisches Krankenhaus Kiel
Kiel, 24116
Greece1 site
General Hospital of Thessaloniki,3rd Dept of Pediatrics
Thessaloniki, 54642
About this study
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
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.
- Being tested
- AZLI, Placebo
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZLIDrug
Also called Cayston®, Aztreonam
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.
PlaceboDrug
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 group | Role | What they receive |
|---|---|---|
| AZLI + Placebo | Experimental | 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. Receives: Drug: AZLI; Drug: Placebo |
| AZLI | Experimental | 75 mg/ml of aztreonam will be administered TID for 28 days. Receives: Drug: AZLI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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 outcomes (3)
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.
Measured: 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)
Measured: 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
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).
Measured: Last dose date of AZLI up to Week 112
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2017
- Study start28 Nov 2017
- Primary completion27 May 2020
- Study completion23 Sep 2021
Why it stopped: Study was terminated early by sponsor due to the challenges and risks introduced by Coronavirus disease 2019 (COVID-19) pandemic.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pseudomonas Aeruginosa Respiratory Tract Infection/ColonizationStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 149 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03219164
- Sponsor's protocol ID
- GS-US-205-1850
- Other IDs
- 2016-002749-42, 2016
- Acronym
- ALPINE 2
- Status last verified
- May 2022
- First submitted
- 13 Jul 2017
- Last updated
- 14 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/
Publications
Gilchrist FJ, Bui S, Gartner S, McColley SA, Tiddens H, Ruiz G, Stehling F, Alani M, Gurtovaya O, Bresnik M, Watkins TR, Frankovic B, Skov M; ALPINE2 study investigators. ALPINE2: Efficacy and safety of 14-day vs 28-day inhaled aztreonam for Pa eradication in children with cystic fibrosis. J Cyst Fibros. 2024 Jan;23(1):80-86. doi: 10.1016/j.jcf.2023.06.008. Epub 2023 Jul 15.
PubMed 37455237
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03219164
- Acronym / sponsor ID
- ALPINE 2 / GS-US-205-1850
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated early by sponsor due to the challenges and risks introduced by Coronavirus disease 2019 (COVID-19) pandemic.
- Enrolment
- 149 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 28 Nov 2017 (actual)
- Primary completion
- 27 May 2020 (actual)
- Study completion
- 23 Sep 2021 (actual)
- First posted
- 17 Jul 2017 (actual)
- Results
- Posted 16 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZLI + Placebo | Experimental | Drug: AZLI, Drug: Placebo75 mg/ml of aztreonam will be administered thrice daily (TID) for 14 days followed by placebo to match (PTM) aztreonam TID for 14 days. |
| AZLI | Experimental | Drug: AZLI75 mg/ml of aztreonam will be administered TID for 28 days. |
Who may qualify
- Ages
- 3 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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 (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZLIAlso: Cayston®, AztreonamAdministered 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. | Drug | AZLI, AZLI + Placebo |
| PlaceboAdministered 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. | Drug | AZLI + Placebo |
Primary outcome
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)
3 secondary outcomes
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37455237Gilchrist FJ, Bui S, Gartner S, McColley SA, Tiddens H, Ruiz G, Stehling F, Alani M, Gurtovaya O, Bresnik M, Watkins TR, Frankovic B, Skov M; ALPINE2 study investigators. ALPINE2: Efficacy and safety of 14-day vs 28-day inhaled aztreonam for Pa eradication in children with cystic fibrosis. J Cyst Fibros. 2024 Jan;23(1):80-86. doi: 10.1016/j.jcf.2023.06.008. Epub 2023 Jul 15.
- Individual participant dataSharing planned: Yes. 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/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
53 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AZLI in people with Pseudomonas Aeruginosa Respiratory Tract Infection/Colonization and Cystic Fibrosis, run by Gilead Sciences at 53 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, United Kingdom, Spain, Italy, Israel and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03219164, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2022.