Efficacy and Safety Study of AeroVanc for the Treatment of Persistent MRSA Lung Infection in Cystic Fibrosis Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Synteract, Inc.
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Savara Inc.
ClinicalTrials.gov Identifier:
NCT01746095
First received: December 6, 2012
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to determine whether AeroVanc treatment is safe and effective in reducing the number of MRSA colony forming units in the lungs of cystic fibrosis patients.


Condition Intervention Phase
Cystic Fibrosis
Drug: Vancomycin inhalation powder
Drug: Placebo inhalation powder
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double Blind, Placebo-controlled Study of AeroVanc for the Treatment of Persistent Methicillin-resistant Staphylococcus Aureus Lung Infection in Cystic Fibrosis Patients

Resource links provided by NLM:


Further study details as provided by Savara Inc.:

Primary Outcome Measures:
  • Change from Baseline at Day 29 of the dosing period (start of AeroVanc/Placebo administration is considered Day 1 of the dosing period) in the number of MRSA colony forming units (CFU) in sputum culture. [ Time Frame: Day 29 of treatment period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in each pulmonary function test (PFT) [ Time Frame: Days 8, 15 and 29 of treatment period ] [ Designated as safety issue: Yes ]
  • Change from Baseline in Cystic Fibrosis Respiratory Symptom Diary (CF-RSD) scores. [ Time Frame: Days 8, 15 and 29 of treatment period ] [ Designated as safety issue: No ]
  • Change from Baseline in MRSA sputum density. [ Time Frame: Days 8 and 15 of treatment period ] [ Designated as safety issue: No ]
  • Time from start of dosing to first administration of other antimicrobial medications (oral, intravenous and/or inhaled) due to respiratory symptoms. [ Time Frame: Entire study: Day 1 of treatment period through 8 week post-treamtent follow up visit ] [ Designated as safety issue: No ]
  • Time from start of dosing to exacerbation of signs/symptoms (Fuchs criteria). [ Time Frame: Entire study: Day 1 of treatment period through 8 week post-treamtent follow up visit ] [ Designated as safety issue: No ]
  • Change from Baseline in high sensitivity CRP and blood neutrophils [ Time Frame: Day 29 of the dosing period ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 80
Study Start Date: March 2013
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vancomycin inhalation powder
32 or 64 mg twice daily (BID)
Drug: Vancomycin inhalation powder
There will be two treatment cohorts in this study, each comprised of 40 randomized (1:1 active to placebo) and treated patients (adults ≥18 and children ≥12 years of age). In Cohort 1, patients will be enrolled and randomized to receive the 32 mg dose of AeroVanc bid or placebo bid. Prior to starting enrollment in Cohort 2, a safety evaluation will be carried out by the Data Monitoring Committee (DMC) based on treatment data from the first 20 patients in Cohort 1. Subject to the Sponsor's written communication of the DMC's opinion of acceptable safety, the dose for the active arm in Cohort 2 will be escalated to 64 mg bid. Optionally, the active arm for Cohort 2 may also be kept the same (32 mg bid), or reduced to 16 mg bid, depending on the outcome of the DMC's safety evaluation.
Other Name: AeroVanc
Placebo Comparator: Placebo inhalation powder
Matching placebo inhaled BID
Drug: Placebo inhalation powder

Detailed Description:

This is a Phase 2a 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 CF patients. Pharmacokinetics will be evaluated in a subgroup by measuring plasma and sputum concentrations of vancomycin.

Prior to treatment, patients will be randomized to receive either AeroVanc twice daily (bid), or placebo bid. Patients will be stratified based on the presence of a Pseudomonas aeruginosa (P. aeruginosa) co-infection that is being treated with a chronic suppression regimen. Patients with P. aeruginosa co-infection can be on any chronic inhaled suppression regimen (or nothing if the patient is considered stable in the opinion of the investigator despite the lack of treatment). Regardless of treatment regimen, if there is an off month, screening should be scheduled so that AeroVanc or placebo administration can be given during this time. Patients with no off month should be screened so that the AeroVanc or placebo administration period coincides with a treatment cycle other than TOBI (e.g., Cayston or colistin). All patients must have at least a 24-hour washout period after stopping their anti-Pseudomonas therapy and prior to the Visit 2 (Baseline) pre-dose microbiology sputum sample. The AeroVanc or placebo treatment duration is 28 days, during which efficacy and safety parameters will be measured, and after which patients will be followed up for 56 days.

There will be two treatment cohorts in this study, each comprised of 40 randomized (1:1 active to placebo) and treated patients (adults ≥18 and children ≥12 years of age). In Cohort 1, patients will be enrolled and randomized to receive the 32 mg dose of AeroVanc bid or placebo bid. Prior to starting enrollment in Cohort 2, a safety evaluation will be carried out by the Data Monitoring Committee (DMC) based on treatment data from the first 20 patients in Cohort 1. Subject to the Sponsor's written communication of the DMC's opinion of acceptable safety, the dose for the active arm in Cohort 2 will be escalated to 64 mg bid. Optionally, the active arm for Cohort 2 may also be kept the same (32 mg bid), or reduced to 16 mg bid, depending on the outcome of the DMC's safety evaluation.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adults ≥18 years old (and the legally authorized representatives of children ≥12 but <18 years old): Able to communicate with site personnel and to understand and voluntarily sign the Informed Consent Form (ICF). Children ≥12 but <18 years old: Able to communicate with site personnel and to understand and voluntarily sign the Assent Form.
  2. Able and willing to comply with the protocol, including availability for all scheduled study visits.
  3. Have a confirmed diagnosis of CF, determined by having clinical features consistent with the CF phenotype, plus one of the following: a) Positive sweat chloride test (value ≥60 mEq/L), or b) Genotype with two mutations consistent with CF (ie, a mutation in each of the cystic fibrosis transmembrane conductance regulator [CFTR] genes).
  4. Be ≥12 years old at time of ICF/Assent Form signing.
  5. Have sputum culture positive for MRSA at Screening, with at least 10,000 CFUs/mL of MRSA.
  6. In addition to the screening sample, have at least two historical respiratory tract cultures (i.e., sputum and/or throat swab) positive for MRSA prior to Screening and evidence that the MRSA lung infection has persisted for at least 6 months prior to Screening.
  7. Have forced expiratory volume in 1 second (FEV1) ≥30% and ≤100% of predicted that is normalized for age, gender, and height at Screening.
  8. Evidence, defined as one or both of the following, that the persistent MRSA lung infection is suspected to be causing health consequences.

    • Have had at least one episode of acute pulmonary infection treated with non-maintenance antibiotics within 12 months from Screening. Initiation of treatment with intermittent inhaled anti-Pseudomonas therapy will not qualify as treatment with non-maintenance antibiotics.
    • Requires anti-MRSA treatment as part of a maintenance regimen to prevent pulmonary exacerbations or other respiratory symptoms.
  9. Be able to perform all the techniques necessary to use the AeroVanc inhaler and measure lung function.
  10. Be able to produce expectorated sputum samples or be able and willing to undergo standardized sputum induction.
  11. Agree not to smoke from Screening through the end of the study.
  12. Female patients of child-bearing potential are eligible to participate in this study only if they are NOT pregnant or lactating, and if the patient is using a highly effective method of birth control.
  13. Patients with P. 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. Patients on a Cayston based therapy must have received at least 2 cycles of Cayston prior to Baseline (can be 2 consecutive months or 2 cycles over 4 months).

Exclusion Criteria:

  1. Administration of any investigational drug or device within 28 days prior to ICF/Assent Form signing.
  2. Use of iv or inhaled anti-MRSA drugs within 28 days or oral anti-MRSA drugs within 14 days prior to Visit 2 (ie, randomization, Baseline and AeroVanc/placebo treatment initiation).
  3. A 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. History of severe cough/bronchospasm upon inhalation of dry powder inhalation product, or nebulized vancomycin.
  5. Resistance to vancomycin at Screening (vancomycin resistant Staphylococcus aureus [VRSA], or vancomycin intermediate resistant Staphylococcus aureus [VISA], with minimum inhibitory concentration [MIC] ≥4 mcg/mL).
  6. Oral corticosteroids in doses exceeding 10 mg prednisone per day or 20 mg prednisone every other day, or equipotent doses of another corticosteroid.
  7. History of sputum culture or throat swab culture yielding B. cepacia or gladioli in the previous two years, or nontuberculosis mycobacteria in the previous six months.
  8. An acute upper or lower respiratory infection, or pulmonary exacerbation within 7 days prior to Randomization.
  9. Changes in antimicrobial, bronchodilator, anti-inflammatory or corticosteroid medications within 7 days prior to ICF/Assent Form signing.
  10. Current daily continuous oxygen supplementation or requirement for more than 2 L/min at night.
  11. Changes in physiotherapy technique or schedule within 7 days prior to ICF/Assent Form signing.
  12. History of lung or other solid organ transplantation or currently on the list to receive lung or other solid organ transplantation.
  13. A chest X-Ray at Screening with abnormalities indicating a significant acute finding (eg, pneumothorax, or pleural effusion).
  14. Lactating female or female with a positive pregnancy test result. All women of childbearing potential will be tested.
  15. Renal insufficiency, defined as creatinine clearance <50 mL/min using the Cockcroft-Gault equation for adults or Schwartz equation in children, at Screening.
  16. Diagnosed with clinically significant hearing loss.
  17. Abnormal liver function, defined as ≥4x upper limit of normal (ULN), of serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT), or known cirrhosis at the time of Screening.
  18. Serum hematology or chemistry screening results which in the judgment of the Investigator would interfere with completion of the study.
  19. Positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
  20. Other findings or medical history at screening that, in the Investigator's opinion, would compromise the safety of the patient or the quality of the study data.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01746095

  Hide Study Locations
Locations
United States, Alabama
Pulmonary Associates of Mobile
Mobile, Alabama, United States, 36608
United States, Arkansas
University of Arkansas for Medical Science
Little Rock, Arkansas, United States, 72205
United States, California
Children's Hospital Los Angeles, Division of Pediatric Pulmonology
Los Angeles, California, United States, 90027
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
United States, Florida
Joe DiMaggio Children's Hospital
Hollywood, Florida, United States, 33021
University of Miami - Miller School of Medicine
Miami, Florida, United States, 33136
Central Florida Pulmonary Group
Orlando, Florida, United States, 32803
Nemours Children's Clinic and Hospital
Orlando, Florida, United States, 32806
New Lung Associates, PA; Lung Transplant, Adult Cystic Fibrosis, and the Center for Advanced Lung Diseases, Tampa General Hospital
Tampa, Florida, United States, 33606
United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
The Cystic Fibrosis Center of Chicago
Glenview, Illinois, United States, 60025
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Kentucky
University of Kentucky Cystic Fibrosis Clinic
Lexington, Kentucky, United States, 40536
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Massachusetts General Hospital Pediatric Cystic Fibrosis Center
Boston, Massachusetts, United States, 02114
Boston Children's Hospital Cystic Fibrosis Center
Boston, Massachusetts, United States, 02115
United States, Michigan
Wayne State University, Harper Hospital, Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New Jersey
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08901
United States, New York
Hofstra North Shore - Long Island Jewish School of Medicine
New Hyde Park, New York, United States, 11040
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Rainbow Babies and Children's Hospital / University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
The Children's Medical Center of Dayton
Dayton, Ohio, United States, 45404
United States, Oklahoma
Santiago Reyes, MD
Oklahoma City, Oklahoma, United States, 73112
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Dell Children's Medical Center of Central Texas
Austin, Texas, United States, 78723
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Baylor College of Medicine and Texas Children's Hospital
Houston, Texas, United States, 77030
University of Texas Health Science Center at Tyler
Tyler, Texas, United States, 75708
United States, Utah
University of Utah, Intermountain Cystic Fibrosis Center
Salt Lake City, Utah, United States, 84132
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Savara Inc.
Synteract, Inc.
Cystic Fibrosis Foundation
Investigators
Principal Investigator: Elliott Dasenbrook, M.D., MHS Case Western Reserve University School of Medicine and Rainbow Babies and Children's Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Savara Inc.
ClinicalTrials.gov Identifier: NCT01746095     History of Changes
Other Study ID Numbers: SAV005-02
Study First Received: December 6, 2012
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Savara Inc.:
Cystic Fibrosis
MRSA
Methicillin-resistant Staphylococcus aureus
Lung infection
AeroVanc
Vancomycin

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Staphylococcal Infections
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Gram-Positive Bacterial Infections
Bacterial Infections
Methicillin
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014