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

NCT03219164 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-205-18502016-002749-42
• Study Type: interventional
• Target: 149
• Locations: 12 countries
• Sites: 53

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.

Conditions

Pseudomonas Aeruginosa Respiratory Tract Infection/Colonization; Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Time From Primary Eradication to PA Recurrence Over a 108-Week Post-Treatment Follow-up Period

  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)

  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

  Last dose date of AZLI up to Week 112

Study Arms (2)

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.

Drug: AZLI; Drug: Placebo

AZLI

EXPERIMENTAL

75 mg/ml of aztreonam will be administered TID for 28 days.

Drug: AZLI

Interventions

AZLI DRUG

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.

Also known as: Cayston®, Aztreonam

AZLI; AZLI + Placebo

Placebo DRUG

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.

AZLI + Placebo

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (53)

University of California San Francisco (UCSF) - Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

Location

Johns Hopkins All Children's Hospital Outpatient Care Center

St. Petersburg, Florida, 33701, United States

Location

Ann & Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Corner Children's Hospital

Chicago, Illinois, 60637, United States

Location

University of Mississippi Medical center

Jackson, Mississippi, 39216, United States

Location

Clinical Research of Charlotte

Charlotte, North Carolina, 28277, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

USC Department of Pediatrics/Division of Pediatric Pulmonology

Columbia, South Carolina, 29203, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

The University of Texas Health Science Center at Tyler

Tyler, Texas, 75708, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Medizinische Universitat Graz

Graz, 8036, Austria

Location

Medizinische Universitat Innsbruck

Innsbruck, 06020, Austria

Location

Hopital Universitaire des Enfants Reine Fabiola

Brussels, 1020, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Hopital des enfants - GH Pellegrin

Bordeaux, 33076, France

Location

CHU Grenoble Alpes

Grenoble, 38043, France

Location

Hopital Robert Debre APHP

Paris, 75019, France

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

Stadtisches Krankenhaus Kiel

Kiel, 24116, Germany

Location

General Hospital of Thessaloniki,3rd Dept of Pediatrics

Thessaloniki, 54642, Greece

Location

Rambam Health Corporation

Haifa, 3109601, Israel

Location

Lady Davis Carmel Medical Center

Haifa, 3436212, Israel

Location

Hadassah University Hospital Mount Scopus

Jerusalem, 9765422, Israel

Location

Schneider Children's Medical Center of Israel

Petah Tikva, 4920230, Israel

Location

Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele

Catania, 95123, Italy

Location

Fondazione IRCCS ca Granda

Milan, 20122, Italy

Location

Azienda Ospedaliera Universitaria "Federico II"

Napoli, 80131, Italy

Location

Azienda Policlinico Umberto - Universita La Sapienza di Roma

Roma, 00161, Italy

Location

Ospedale Pediatrico Bambino Gesu

Roma, 00165, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona

Verona, 37126, Italy

Location

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Hospital Universitario Vall d Hebron

Barcelona, 08035, Spain

Location

Hospital Sant Joan de Deu

Esplugues de Llobregat, 08950, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29011, Spain

Location

Corporacio Sanitaria Parc Tauli

Sabadell, 08208, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario

Valencia, 46010, Spain

Location

NHS Grampian

Aberdeen, AB25 2ZG, United Kingdom

Location

Birmingham Children's Hospital NHS Foundation Trust

Birmingham, B4 6NH, United Kingdom

Location

Royal Devon and Exeter Foundation NHS Trust

Exeter, EX2 5DW, United Kingdom

Location

University Hospitals of Leicester NHS trust

Leicester, LE1 5WW, United Kingdom

Location

Barts and the London Children's Hospital

London, E1 1BB, United Kingdom

Location

Kings College Hospital NHS foundation Trust

London, SE5 9RS, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

South Tees Hospitals NHS Foundation Trust

Middlesbrough, TS4 3BW, United Kingdom

Location

Sheffield Children's Hospital NHS Trust

Sheffield, S10 2TH, United Kingdom

Location

Southampton University Hospitals NHS trust, Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

University Hospitals of North Midlands NHS trust Royal Stoke University Hospital

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37455237 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Aztreonam

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Monobactams; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The study was terminated early due to Coronavirus disease 2019 (COVID-19) pandemic. At the time of study termination, all evaluable participants completed the initial eradication period and provided data for the primary analysis.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2017
• First Posted: July 17, 2017
• Study Start: November 28, 2017
• Primary Completion: May 27, 2020
• Study Completion: September 23, 2021
• Last Updated: June 14, 2022
• Results First Posted: May 16, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

DK (2); FR (3); US (12); IL (4); AU (2); BE (2); IT (6); NL (1); ES (7); GR (1); GB (11); DE (2)