AeroVanc in the Treatment of Methicillin-resistant Staphylococcus Aureus Infection in Patients With Cystic Fibrosis
NCT ID: NCT03181932
Last Updated: 2022-12-16
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
188 participants
INTERVENTIONAL
2017-09-20
2021-01-15
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Double-blind 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.
Vancomycin inhalation powder
100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Double-blind 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.
Placebo inhalation powder
100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Open-label 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.
Vancomycin inhalation powder
In the 24-week Period 2, all participants are to be treated with open-label vancomycin inhalation powder.
Interventions
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Vancomycin inhalation powder
100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Placebo inhalation powder
100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Vancomycin inhalation powder
In the 24-week Period 2, all participants are to be treated with open-label vancomycin inhalation powder.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Confirmed diagnosis of CF, determined by having clinical features consistent with the CF phenotype, plus one of the following:
1. Positive sweat chloride test (value ≥60 milliequivalent/L),
2. Genotype with 2 mutations consistent with CF (i.e., a mutation in each of the cystic fibrosis transmembrane conductance regulator genes).
3. Positive sputum culture or a throat swab culture for MRSA at Screening.
4. In addition to the Screening sample, have at least 2 prior sputum or throat swab cultures positive for MRSA, of which at least 1 sample is \>6 months prior to Screening. At least 50% of all MRSA cultures (sputum or throat swab culture) collected from the time of the first positive culture (in the previous 1 year) must have tested positive for MRSA. (Note: Screening sample may count towards 50% positive count)
5. FEV1 ≥30% and ≤90% of predicted that is normal for age, gender, race, and height, using the Global Lung Function Initiative equation.
6. At least 1 episode of acute pulmonary infection treated with non-maintenance antibiotics within 12 months prior to the Baseline visit (initiation of treatment with intermittent inhaled anti-Pseudomonal therapy will not qualify as treatment with non-maintenance antibiotics).
7. If female of childbearing potential, an acceptable method of contraception must be used during the study and must be combined with a negative pregnancy test obtained during Screening; sexually active male subjects of reproductive potential who are non-sterile (i.e., male who has not been sterilized by vasectomy for at least 6 months, and were not diagnosed with infertility through demonstration of azoospermia in a semen sample and/or absence of vas deferens through ultrasound) must be willing to use a barrier method of contraception, or their female partner must use an acceptable method of contraception, during the study.
For purposes of this study, the Sponsor defines "acceptable methods of contraception" as:
1. Oral birth control pills administered for at least 1 monthly cycle prior to administration of the study drug.
2. A synthetic progestin implanted rod (eg, Implanon®) for at least 1 monthly cycle prior to the study drug administration but not beyond the 4th successive year following insertion.
3. Intrauterine devices, inserted by a qualified clinician for at least 1 monthly cycle prior to study drug administration.
4. Medroxyprogesterone acetate (eg, Depo-Provera®) administered for a minimum of 1 monthly cycle prior to administration of the study drug and continuing through 1 month following study completion.
5. Hysterectomy or surgical sterilization.
6. Abstinence.
7. Double barrier method (diaphragm with spermicidal gel or condoms with contraceptive foam).
Note: For subjects prescribed Orkambi: Orkambi may substantially decrease hormonal contraceptive exposure, reducing the effectiveness and increasing the incidence of menstruation-associated adverse reactions. Hormonal contraceptives, including oral, injectable, transdermal, and implantable, should not be relied upon as an effective method of contraception when co-administered with Orkambi.
8. Able and willing to comply with the protocol, including availability for all scheduled study visits and able to perform all techniques necessary to use the AeroVanc inhaler and measure lung function.
9. Agree not to smoke during any part of the clinical trial (Screening visit through end of study).
10. Participants with a Pseudomonas aeruginosa co-infection must either be stable on a regular suppression regimen of inhaled antibiotics or must be, in the opinion of the Investigator, stable despite the lack of such treatment.
Exclusion Criteria
2. Use of non-maintenance antibiotic for pulmonary infection or extrapulmonary MRSA infection (IV or inhaled antibiotic within 28 days; oral antibiotic within 14 days) prior to the Baseline visit.
3. History of previous allergies or sensitivity to vancomycin, or other component(s) of the study drug or placebo except for a history of red-man syndrome.
4. Inability to tolerate inhaled products.
5. First time sputum culture or throat swab culture yielding Burkholderia cepacia, or nontuberculous Mycobacteria in the previous 6 months to Screening.
6. History of lung or other solid organ transplantation or currently on the list to receive lung or other solid organ transplantation.
7. Resistance to vancomycin at Screening (vancomycin resistant Staphylococcus aureus, or vancomycin intermediate resistant Staphylococcus aureus, with minimum inhibitory concentration ≥8 μg/mL).
8. Oral corticosteroids in doses exceeding 10 mg prednisone per day or 20 mg prednisone every other day, or equipotent doses of other corticosteroids.
9. Changes in antimicrobial, bronchodilator, anti-inflammatory or corticosteroid medications within 14 days, or changes in cystic fibrosis transmembrane conductance modulators within 28 days, prior to the Baseline visit.
10. Abnormal laboratory findings or other findings or medical history at Screening that, in the Investigator's opinion, would compromise the safety of the subject or the quality of the study data.
11. Inability to tolerate inhalation of a short acting beta2 agonist
12. Oxygen saturation \<90% at Screening.
13. Changes in physiotherapy technique or physiotherapy scheduled within 1 week of the Baseline visit.
14. Administration of any investigational drug or device within 4 weeks prior to the Screening visit and during the study
15. Female with positive pregnancy test result during Screening, pregnant (or intends to become pregnant), lactating or intends to breastfeed during the study.
16. Renal insufficiency, defined as creatinine clearance \<50 mL/min using the Cockcroft-Gault equation for adults or Schwartz equation for children at the Screening visit.
17. Abnormal liver function, defined as ≥4x upper limit of normal of serum aspartate aminotransferase or serum alanine aminotransferase, or known cirrhosis at Screening.
18. Diagnosed with clinically significant hearing loss.
19. History of positive result for human immunodeficiency virus, hepatitis B virus or hepatitis C virus.
20. Planned hospitalizations for prophylaxis antibiotic treatment within 28 days prior to Baseline visit or during the double-blind period (Period 1).
6 Years
ALL
No
Sponsors
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Savara Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Patrick Flume, MD
Role: PRINCIPAL_INVESTIGATOR
Medical University of South Carolina
Locations
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Pulmonary Associates of Mobile
Mobile, Alabama, United States
Phoenix Children's Hospital
Phoenix, Arizona, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Miller Childrens Hospital MemorialCare Health System Pediatric Pulmonology
Long Beach, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
University of Southern California Keck Medical Center of USC
Los Angeles, California, United States
UC Davis Medical Center
Sacramento, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
National Jewish Health Adult Cystic Fibrosis Center
Denver, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Florida Pediatrics
Gainesville, Florida, United States
Memorial Healthcare System
Hollywood, Florida, United States
Nemours Childrens Specialty Care
Jacksonville, Florida, United States
University of Miami Bachelor Children's Hospital
Miami, Florida, United States
Central Florida Pulmonary Group
Orlando, Florida, United States
Arnold Palmer Hospital Pulmonary and Sleep Medical Institute Orlando Health, Inc
Orlando, Florida, United States
Nemours Children's Hospital
Orlando, Florida, United States
Nemours Children's Specialty Care
Pensacola, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Children's Health Care of Atlanta at Scottish Rite
Atlanta, Georgia, United States
Augusta Univ Cystic Fibrosis Center
Augusta, Georgia, United States
Chicago CF Care Specialists
Glenview, Illinois, United States
NorthSurburban Pulmonary Specialists
Morton Grove, Illinois, United States
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, United States
University of Iowa Department of Pediatrics
Iowa City, Iowa, United States
University of Kansas
Kansas City, Kansas, United States
Via Christi Health Systems CF Clinic
Wichita, Kansas, United States
University of Louisville Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, United States
Maine Medical Partners Pediatric Specialty Care
Portland, Maine, United States
Boston Children's Hospital
Boston, Massachusetts, United States
University of Michigan Health System
Ann Arbor, Michigan, United States
Wayne State University (HUH)
Detroit, Michigan, United States
Children's Mercy
Kansas City, Missouri, United States
Cardinal Glennon Children's Hospital /Saint Louis University
St Louis, Missouri, United States
Washington University
St Louis, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Morristown Medical Center
Morristown, New Jersey, United States
Rutgers-Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States
University of New Mexico Pediatric/Pulmonary
Albuquerque, New Mexico, United States
Albany Medical College
Albany, New York, 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
Duke University Medical Center
Durham, North Carolina, United States
Wake Forest School of Medicine
Winston-Salem, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
University Hospital Cleveland Medical Center
Cleveland, Ohio, United States
The Research Institute at Nationwide Children's Hospital
Columbus, Ohio, United States
Dayton Children's Hospital
Dayton, Ohio, United States
Toledo Children's Hospital CF Center
Toledo, Ohio, United States
University of Oklahoma Health Science Center - Pediatric Pulmonary & CF Center
Oklahoma City, Oklahoma, United States
Oregon Health and Science University
Portland, Oregon, United States
Penn State Children's Hospital
Hershey, Pennsylvania, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMCU
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina (MUSC)
Charleston, South Carolina, United States
Sanford Childrens Specialty Clinic
Sioux Falls, South Dakota, United States
UTHSC Lebonheur Children's Hospital
Memphis, Tennessee, United States
Austin Children's Chest Associates
Austin, Texas, United States
Children's Medical Center Cystic Fibrosis Clinic
Dallas, Texas, United States
Cook Children Medical Center
Fort Worth, Texas, United States
Texas Children's Hospital
Houston, Texas, United States
The University of Texas Health Science Center at Tyler
Tyler, Texas, United States
University of Utah Health Sciences Center
Salt Lake City, Utah, United States
University Vermont Medical Center Vermont Lung Center
Colchester, Vermont, United States
University of Virginia Health System, Cystic Fibrosis Center
Charlottesville, Virginia, United States
Seattle Children's Hospital
Seattle, Washington, United States
Providence Medical Research Center
Spokane, Washington, United States
West Virginia University
Morgantown, West Virginia, United States
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
The Hospital for Sick Children
Toronto, Ontario, Canada
Countries
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References
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Lo DK, Muhlebach MS, Smyth AR. Interventions for the eradication of meticillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis. Cochrane Database Syst Rev. 2022 Dec 13;12(12):CD009650. doi: 10.1002/14651858.CD009650.pub5.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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SAV005-04
Identifier Type: -
Identifier Source: org_study_id