Clinical trial NCT03219164: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pseudomonas Aeruginosa Respiratory Tract Infection/Colonization
Cystic Fibrosis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2017-07-17
Enrollment: 149
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
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
timeFrame: 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:
measure: Time From Primary Eradication to PA Recurrence Over a 108-Week Post-Treatment Follow-up Period
timeFrame: Last dose date of AZLI up to Week 112
measure: 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)
timeFrame: 28 days post treatment (Weeks 4 to 6 for the 14 Day treatment group)
measure: 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
timeFrame: Last dose date of AZLI up to Week 112
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF) - Benioff Children's Hospital
state: California
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital Outpatient Care Center
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H Lurie Childrens Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Corner Children's Hospital
state: Illinois
city: Jackson
country: United States
facility: University of Mississippi Medical center
state: Mississippi
city: Charlotte
country: United States
facility: Clinical Research of Charlotte
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbia
country: United States
facility: USC Department of Pediatrics/Division of Pediatric Pulmonology
state: South Carolina
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Tyler
country: United States
facility: The University of Texas Health Science Center at Tyler
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Graz
country: Austria
facility: Medizinische Universitat Graz
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
city: Brussels
country: Belgium
facility: Hopital Universitaire des Enfants Reine Fabiola
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Bordeaux
country: France
facility: Hopital des enfants - GH Pellegrin
city: Grenoble
country: France
facility: CHU Grenoble Alpes
city: Paris
country: France
facility: Hopital Robert Debre APHP
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Kiel
country: Germany
facility: Stadtisches Krankenhaus Kiel
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki,3rd Dept of Pediatrics
city: Haifa
country: Israel
facility: Rambam Health Corporation
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Mount Scopus
city: Petah Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
city: Milano
country: Italy
facility: Fondazione IRCCS ca Granda
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico II"
city: Roma
country: Italy
facility: Azienda Policlinico Umberto - Universita La Sapienza di Roma
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d Hebron
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario
city: Aberdeen
country: United Kingdom
facility: NHS Grampian
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital NHS Foundation Trust
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Foundation NHS Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS trust
city: London
country: United Kingdom
facility: Barts and the London Children's Hospital
city: London
country: United Kingdom
facility: Kings College Hospital NHS foundation Trust
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospitals NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital NHS Trust
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals NHS trust, Southampton General Hospital
city: Stoke on Trent
country: United Kingdom
facility: University Hospitals of North Midlands NHS trust Royal Stoke University Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: