MP-376 (Aeroquin™, Levofloxacin for Inhalation) in Patients With Cystic Fibrosis

Phase 3

Completed

Conditions: Cystic Fibrosis

Interventions: Drug: Aeroquin
Drug: Placebo

Registration Number: NCT01180634

Lead Sponsor: Amgen

Brief Summary: Patients with cystic fibrosis (CF) suffer from chronic infections of the lower respiratory tract that can be caused by one or multiple bacteria, including Pseudomonas aeruginosa, which has been particularly problematic to eradicate and been implicated as the major cause of morbidity and mortality in CF patients. Aerosol delivery of antibiotics directly to the lung increases the local concentrations of antibiotic at the site of infection resulting in improved antimicrobial effects compared to systemic administration. Decreased efficacy, intolerance and high treatment burden with currently available therapies indicate a need for additional therapies. MP-376 (Aeroquin™) is a novel formulation of the fluoroquinolone levofloxacin that has been optimized for aerosol delivery. Preclinical and clinical studies conducted to date show that aerosol doses of MP-376 are safe and well tolerated, exert an antimicrobial effect, improve lung function and reduce the need for other anti-pseudomonal antibiotics. High concentrations of levofloxacin in the lung delivered as MP-376 are active against CF pathogens including those with high minimum inhibitory concentration (MIC) levels to aminoglycosides such as tobramycin (TOBI®) and other inhaled antimicrobial agents. Inhaled MP-376 can be delivered rapidly and efficiently using a customized PARI investigational configuration of the eFlow® nebulizer system.

Detailed Description: This trial will be a double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin administered as MP-376 given for 28 days by the aerosol route to CF patients.

Study with completed results acquired from Horizon in 2024.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 330

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aeroquin 240 mg	Aeroquin	Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.
Placebo	Placebo	Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.

Primary Outcome Measures

Name	Time	Method
Time to an Exacerbation	Baseline to end of study (up to 59 days)	The start of the exacerbation was determined by the earliest date at which a participant concurrently met at least 4 of the 12 modified Fuchs symptoms/signs; discontinued from the study early; died; or received an antipseudomonal agent for an event that did not meet modified Fuchs criteria but was determined to be an exacerbation by the Blinded Exacerbation. Fuchs symptoms/signs; * Change in sputum * New or increased hemoptysis * Increased cough * Increased dyspnea * Malaise, fatigue or lethargy * Temperature above 38oC * Anorexia or weight loss * Sinus pain or tenderness * Change in sinus discharge * Change in physical examination of the chest * Decrease in pulmonary function by 10 percent or more from a previously recorded value * Radiographic changes indicative of pulmonary infection Median and 95%Ci were estimated using Kaplan Meier estimates.

Secondary Outcome Measures

Name	Time	Method
Time to Administration of Other Systemic and/or Inhaled Antipseudomonal Antimicrobials	Baseline to end of study (up to 59 days)	Participants who had at least one of four worsening respiratory symptoms (increased cough, increased sputum/chest congestion, decreased exercise tolerance, decreased appetite) at the time of administration of the anti-pseudomonal antimicrobial agent were included in the analysis. Median and 95% CI are estimated using Kaplan Meier estimates.
Absolute Change in Percent Predicted Forced Expiratory Volume in One Second (FEV1)	Baseline, day 28	FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer. Least squares (LS) mean and standard error are determined from a repeated measures model with terms for treatment, visit, treatment\*visit, region (US, non-US), age (12-18 years, \>18 years), and baseline FEV1 (\<55%, \>=55%).
Change From Baseline in Pseudomonas Aeruginosa Sputum Density	Baseline, Day 28	Pseudomonas aeruginosa density was measured as log10 colony-forming units \[CFU\] per gram sputum. LSMean and standard are determined from a repeated measures model with terms for treatment, visit, treatment\*visit, region (US, non-US), age (12-18 years, \>18 years), baseline FEV1 (\<55%, \>=55%), and baseline organism log density.
Relative Change From Baseline in Percent Predicted FEV1	Baseline, Day 28	FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer. Least squares (LS) mean and standard error are determined from a repeated measures model with terms for treatment, visit, treatment\*visit, region (US, non-US), age (12-18 years, \>18 years), and baseline FEV1 (\<55%, \>=55%).
Time to First Hospitalization	Baseline to end of study (up to 59 days)	Median and 95%CI was estimated using Kaplan Meier estimates.
Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R)	Baseline, Day 28	The Cystic Fibrosis Questionnaire (CFQ-R) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents and adults with cystic fibrosis (CF). Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. LSMean and standard error were determined from a repeated measures model with terms for treatment, visit, treatment\*visit, region (US, non-US), age (12 to 18 years, \> 18 years), Baseline FEV1 (\<55%, ≥ 55%), and Baseline value.
Number of Participants With Treatment Emergent Adverse Events	From start of study until end of study (Up to 59 days)	An AE was defined as any unfavorable or unintended sign, symptom, or disease temporally associated with the use of a Study Drug, whether or not considered related to the Study Drug. An AE could potentially be a new disease, any untoward event, or an exacerbation of a pre-existing condition. AEs included, but were not limited to: * Any symptom not previously reported by the patient (medical history) * An exacerbation of a pre-existing illness * An increase in frequency or intensity of a pre-existing episodic event or condition * A condition first detected or diagnosed after Study Drug administration even though the condition may have been present before the start of the study * Overdose of Study Drug

Trial Locations

Locations (14): Westmead Chilren's Hospital
🇦🇺
Westmead, New South Wales, Australia
Childrens Hospital
🇺🇸
Los Angeles, California, United States
Mater Miscericordiae Hospital
🇦🇺
Brisbane, Queensland, Australia
Royal Children's Hospital
🇦🇺
Melbourne, Victoria, Australia
The Alfred Hospital
🇦🇺
Melbourne, Victoria, Australia
Hadassah Medical Center Mount Scopus
🇮🇱
Jerusalem, Israel
Schneider Childrens Medical Center of Israel
🇮🇱
Petah Tikva, Israel
Sheba Medical Center
🇮🇱
Ramat-Gan, Israel
Rambam Medical Center
🇮🇱
Haifa, Israel
Monash Medical Center
🇦🇺
Melbourne, Australia
Westmead Hospital
🇦🇺
Westmead, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺
Adelaide, South Australia, Australia
John Hunter Hospital
🇦🇺
New South Wales, Australia
Auckland Hospital
🇳🇿
Auckland, New Zealand