AeroVanc in the Treatment of Methicillin-resistant Staphylococcus Aureus Infection in Patients With Cystic Fibrosis
- Conditions
- Cystic FibrosisMRSA
- Interventions
- Drug: Placebo inhalation powder
- Registration Number
- NCT03181932
- Lead Sponsor
- Savara Inc.
- Brief Summary
This is a multi-center, randomized phase III study to evaluate the clinical effectiveness of AeroVanc in persistent methicillin-resistant Staphylococcus aureus (MRSA) infection in patients with cystic fibrosis (CF).
- Detailed Description
This is a phase III, randomized, multicenter, double-blind, placebo-controlled, parallel-group study to examine the safety and efficacy of AeroVanc in the treatment of persistent MRSA lung infection in patients diagnosed with CF. After the Screening period to confirm study eligibility, participants are randomly assigned in a blinded fashion to receive either AeroVanc 30 mg twice daily (BID), or placebo BID (1:1 active to placebo) by inhalation for 24 weeks or 3 dosing cycles (Period 1). Upon completion of Period 1, participants receive open-label AeroVanc 30 mg BID for an additional 24 weeks or 3 dosing cycles (Period 2), to evaluate long-term safety of AeroVanc. A dosing cycle is defined as 28 days of treatment followed by 28 days of observation.
Participants on a 28-day cyclical on/off anti-Pseudomonal antibiotic regimen enter the Screening period at a time such that the Baseline visit coincide with the end of their anti-Pseudomonas antibiotic cycle. Study drug is thereby administered during the off-cycle, and participants can then resume anti-Pseudomonal therapy during the 28-day observation period. Participants continuing alternating anti-Pseudomonal therapy can continue their treatment during the study drug administration, and observation period.
The primary and secondary analyses are conducted in participants ≤21 years old. Subjects \>21 years old are analyzed separately as supportive analyses.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 188
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open-label vancomycin inhalation powder Vancomycin inhalation powder In the 24-week Period 2, all participants receive AeroVanc 30 mg BID by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Double-blind vancomycin inhalation powder Vancomycin inhalation powder Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Double-blind placebo inhalation powder Placebo inhalation powder Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation.
- Primary Outcome Measures
Name Time Method Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted Baseline and Week 4, 12 and 20 The mean absolute change from baseline in FEV1 percent predicted was analyzed sequentially at Week 4 (end of Cycle 1), Week 12 (end of Cycle 2) and at Week 20 (end of Cycle 3).
- Secondary Outcome Measures
Name Time Method Time to First Pulmonary Exacerbation Week 20 Time to first pulmonary exacerbation requiring use of another antibiotic medication (oral, IV, and/or inhaled). The Outcome Measure Data presented are the median percentiles and 95% confidence intervals from Kaplan-Meier estimates.
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Scores Baseline and Week 4, 12, and 20 The CFQ-R was administered every two weeks using a hand-held e-Diary. CFQ-R scores range between 0 and 100, where higher scores indicate a better outcome. The CFQ-R measures functioning in a variety of domains, including Physical Functioning, Vitality, Health Perceptions, Respiratory Symptoms, Treatment Burden, Role Functioning, Emotional Functioning and Social Functioning. The Outcome Measure Data presented are the Respiratory Symptoms Scores.
Number of Successful Response Cycles Week 20 The number of successful response cycles a participant achieves over Period 1. A response in a cycle is defined by at least a 5 % relative improvement in FEV1 percent predicted at the end of each the respective cycle.
Area Under the FEV1-time Profile Week 20 The mean treatment difference in FEV1 across all post-baseline visits
Frequency of Pulmonary Exacerbations Week 20 The number of pulmonary exacerbations during Period 1 adjusted for the length of follow-up.
Change From Baseline in Cystic Fibrosis Respiratory Symptom Diary-Chronic Respiratory Symptom Score (CFRSD-CRISS) Scores Baseline and Week 4, 12 and 20 The CFRSD-CRISS was administered every two weeks using a hand-held e-Diary. Scores range between 0 and 100, where higher scores indicate a worse outcome.
Relative Change in FEV1 Percent Predicted Baseline and Week 4, 12 and 20 The mean relative change from Baseline in FEV1 percent predicted
Trial Locations
- Locations (71)
University Vermont Medical Center Vermont Lung Center
🇺🇸Colchester, Vermont, United States
Chicago CF Care Specialists
🇺🇸Glenview, Illinois, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Children's Health Care of Atlanta at Scottish Rite
🇺🇸Atlanta, Georgia, United States
The Research Institute at Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospital of Pittsburgh of UPMCU
🇺🇸Pittsburgh, Pennsylvania, United States
University Hospital Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
University of Miami Bachelor Children's Hospital
🇺🇸Miami, Florida, United States
Riley Hospital for Children at Indiana University Health
🇺🇸Indianapolis, Indiana, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University of Utah Health Sciences Center
🇺🇸Salt Lake City, Utah, United States
Via Christi Health Systems CF Clinic
🇺🇸Wichita, Kansas, United States
Maine Medical Partners Pediatric Specialty Care
🇺🇸Portland, Maine, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
Nemours Children's Specialty Care
🇺🇸Pensacola, Florida, United States
Albany Medical College
🇺🇸Albany, New York, United States
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
National Jewish Health Adult Cystic Fibrosis Center
🇺🇸Denver, Colorado, United States
Wayne State University (HUH)
🇺🇸Detroit, Michigan, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Pulmonary Associates of Mobile
🇺🇸Mobile, Alabama, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
University of Southern California Keck Medical Center of USC
🇺🇸Los Angeles, California, United States
Miller Childrens Hospital MemorialCare Health System Pediatric Pulmonology
🇺🇸Long Beach, California, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Nemours Childrens Specialty Care
🇺🇸Jacksonville, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Augusta Univ Cystic Fibrosis Center
🇺🇸Augusta, Georgia, United States
University of Kansas
🇺🇸Kansas City, Kansas, United States
NorthSurburban Pulmonary Specialists
🇺🇸Morton Grove, Illinois, United States
University of Iowa Department of Pediatrics
🇺🇸Iowa City, Iowa, United States
Cardinal Glennon Children's Hospital /Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
University of New Mexico Pediatric/Pulmonary
🇺🇸Albuquerque, New Mexico, United States
Rutgers-Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Northwell Health, Div of Pulmonary, Critical Care & Sleep Medicine
🇺🇸New Hyde Park, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Levine Children's Hospital - Atrium Health
🇺🇸Charlotte, North Carolina, United States
University of Oklahoma Health Science Center - Pediatric Pulmonary & CF Center
🇺🇸Oklahoma City, Oklahoma, United States
Toledo Children's Hospital CF Center
🇺🇸Toledo, Ohio, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
UTHSC Lebonheur Children's Hospital
🇺🇸Memphis, Tennessee, United States
Sanford Childrens Specialty Clinic
🇺🇸Sioux Falls, South Dakota, United States
Children's Medical Center Cystic Fibrosis Clinic
🇺🇸Dallas, Texas, United States
Cook Children Medical Center
🇺🇸Fort Worth, Texas, United States
University of Virginia Health System, Cystic Fibrosis Center
🇺🇸Charlottesville, Virginia, United States
Providence Medical Research Center
🇺🇸Spokane, Washington, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Arnold Palmer Hospital Pulmonary and Sleep Medical Institute Orlando Health, Inc
🇺🇸Orlando, Florida, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Central Florida Pulmonary Group
🇺🇸Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
University of Louisville Kosair Charities Pediatric Clinical Research Unit
🇺🇸Louisville, Kentucky, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Wake Forest School of Medicine
🇺🇸Winston-Salem, North Carolina, United States
The University of Texas Health Science Center at Tyler
🇺🇸Tyler, Texas, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
Children's Mercy
🇺🇸Kansas City, Missouri, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
Austin Children's Chest Associates
🇺🇸Austin, Texas, United States
University of Florida Pediatrics
🇺🇸Gainesville, Florida, United States