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

Cystic Fibrosis Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03219164
• Other study ID #: GS-US-205-1850
• Secondary ID: 2016-002749-42
• Status: Terminated
• Phase: Phase 3
• Start date: November 28, 2017
• Est. completion date: September 23, 2021

Study information

• Verified date: May 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 149
• Est. completion date: September 23, 2021
• Est. primary completion date: May 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 18 Years

Eligibility

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 ß2 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

Related Conditions & MeSH terms

• Communicable Diseases
• Cystic Fibrosis
• Fibrosis
• Infections
• Pseudomonas Infections
• Respiratory Tract Infections

Intervention

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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Denmark,  France,  Germany,  Greece,  Israel,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		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	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.	Last dose date of AZLI up to Week 112
Secondary	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)		28 days post treatment (Weeks 4 to 6 for the 14 Day treatment group)
Secondary	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).	Last dose date of AZLI up to Week 112