Study of Aztreonam for Inhalation in Children With Cystic Fibrosis and New Infection of the Airways by Pseudomonas Aeruginosa Bacteria (ALPINE 2)

Gilead Sciences

Status and phase: Terminated; Phase 3

Conditions: Cystic Fibrosis; Pseudomonas Aeruginosa Respiratory Tract Infection/Colonization

Treatments: Drug: AZLI; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03219164

2016-002749-42 (EudraCT Number)

GS-US-205-1850

Details and patient eligibility

About

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.

Enrollment: 149 patients

Sex: All

Ages: 3 months to 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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149 participants in 2 patient groups

AZLI + Placebo

Experimental group

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.

Treatment:

Drug: AZLI

Drug: Placebo

AZLI

Experimental group

Description:

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

Treatment:

Drug: AZLI