Study of Aztreonam for Inhalation in Children with Cystic Fibrosis and New Infection of the Airways by Pseudomonas aeruginosa bacteria

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2016-002749-42-DE
• Date of registration: 02/08/2017
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: Study of Aztreonam for Inhalation in Children with Cystic Fibrosis and New Infection of the Airways by Pseudomonas aeruginosa bacteria
• Scientific 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 - ALPINE2 (Aztreonam Lysine for Pseudomonas Infection Eradication 2)
• Date of first enrolment: 22/09/2017
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002749-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1) Male or female aged 3 months to less than 18 years at screening
2) Diagnosis of CF as determined by the 2008 CF Consensus Conference criteria
3) 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)
4) FEV1 = 80% predicted
5) Clinically stable with no evidence of acute significant respiratory symptoms that would require administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization
6) A negative serum pregnancy test is required for female subjects of child bearing potential who have a positive urine pregnancy test at screening
7) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
8) Lactating females must agree to discontinue nursing before administration of study drug
9) Subjects and/or parent/guardian must be able to give written informed consent prior to study related procedures
Are the trial subjects under 18? yes
Number of subjects for this age range: 140
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1) Use of IV or inhaled antipseudomonal antibiotics within 2 years of Screening
2) Use of oral antipseudomonal antibiotics for a respiratory event within 30 days of study entry (Screening visit)
3) History of intolerance to inhaled short acting ß2 agonists
4) History of lung transplantation
5) Administration of any investigational drug or device within 28 days prior to Screening
6) Concurrent use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone per day or 20 mg prednisone every other day
7) Current requirement for daily continuous oxygen supplementation or requirement of more than 2 L/minute at night
8) Hospitalization for a respiratory event within 30 days prior to Screening
9) Changes in antimicrobial, bronchodilator, corticosteroid, dornase alfa, or hypertonic saline medications within 7 days prior to Screening
10) Significant changes (per investigators discretion) in physiotherapy technique or schedule within 7 days prior to Screening
11) Abnormal hepatic or renal function results at most recent test within the previous 12 months, defined as
- AST or ALT >5 times upper limit of normal (ULN), or
- Serum creatinine > 2 times ULN for age
12) Presence of a condition or abnormality that would, in the opinion of the Investigator, compromise the subject’s safety or the quality of the study data
13) Known hypersensitivity to aztreonam, its metabolites, or formulation excipients present in AZLI
14) Respiratory cultures performed within 2 years prior to Screening that are positive for ANY Burkholderia spp. or NTM


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Cystic fibrosis and new onset lower respiratory tract culture positive for Pseudomonas aeruginosa
MedDRA version: 22.1 Level: LLT Classification code 10068288 Term: Cystic fibrosis pulmonary exacerbation System Organ Class: 100000004862

Intervention(s)

Trade Name: Cayston
Aztreonam 75 mg powder and solvent for nebuliser solution
Product Code: AZLI
Pharmaceutical Form: Powder and solvent for nebuliser solution
INN or Proposed INN: AZTREONAM
Current Sponsor code: AZLI
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Powder and solvent for nebuliser solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): The primary endpoint of this study is:
- The proportion of subjects with PA-negative cultures through 28 days post-treatment in the 14-day treatment group vs 28-day treatment group

Main Objective: The primary objective of this study is to evaluate the safety and efficacy of a 14-day course vs a 28-day course of AZLI 75 mg three times a day (TID) in subjects with new onset PA respiratory tract colonization/infection as determined by PA eradication over a 28-day post-treatment follow-up period.

Secondary Objective: - To evaluate the time from primary eradication to PA recurrence over a 108-week
post-treatment follow-up period.
- To compare the efficacy of AZLI 75 mg TID for 14 days vs historical pooled tobramycin nebulizer solution (TNS) twice daily (BID) for 28 days as determined by PA eradication over a 28-day post-treatment follow-up period
- To evaluate the time to PA recurrence for a sub-group of subjects matching the population in the TNS ELITE Study over a 108-week post-treatment follow-up period

Timepoint(s) of evaluation of this end point: Day 29

Secondary Outcome(s)

Secondary end point(s): Time from primary eradication to PA recurrence over a 108-week post-treatment follow-up
period
- The proportion of subjects 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 subjects treated with TNS
- Time to PA recurrence for a sub-group of subjects matching the population in the TNS ELITE Study over a 108-week post-treatment follow-up period

Timepoint(s) of evaluation of this end point: Secondary objectives include the evaluations of the time to recurrence of PA from primary eradication over the 108-week post-treatment follow-up period. Primary eradication is defined as all PA-negative cultures through 28 days post AZLI treatment. Cultures will be obtained at week 16 and then at 12-week intervals during the follow-up time frame.

Secondary ID(s)

2016-002749-42-BE

GS-US-205-1850

Source(s) of Monetary Support

Gilead Sciences, Inc.

Ethics review

Status: Approved
Approval date: 22/09/2017
Contact: