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

NCT ID: NCT01746095

Last Updated: 2020-01-13

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-03-31

Study Completion Date

2014-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Vancomycin hydrochloride inhalation powder

32 or 64 mg twice daily (BID)

Group Type EXPERIMENTAL

Vancomycin hydrochloride inhalation powder

Intervention Type DRUG

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.

Placebo inhalation powder

Matching placebo inhalation powder BID

Group Type PLACEBO_COMPARATOR

Placebo inhalation powder

Intervention Type DRUG

Interventions

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Vancomycin hydrochloride 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.

Intervention Type DRUG

Placebo inhalation powder

Intervention Type DRUG

Other Intervention Names

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AeroVanc

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Synteract, Inc.

INDUSTRY

Sponsor Role collaborator

Cystic Fibrosis Foundation

OTHER

Sponsor Role collaborator

Savara Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elliott Dasenbrook, M.D., MHS

Role: PRINCIPAL_INVESTIGATOR

Case Western Reserve University School of Medicine and Rainbow Babies and Children's Hospital

Locations

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Pulmonary Associates of Mobile

Mobile, Alabama, United States

Site Status

University of Arkansas for Medical Science

Little Rock, Arkansas, United States

Site Status

Children's Hospital Los Angeles, Division of Pediatric Pulmonology

Los Angeles, California, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Site Status

University of Miami - Miller School of Medicine

Miami, Florida, United States

Site Status

Central Florida Pulmonary Group

Orlando, Florida, United States

Site Status

Nemours Children's Clinic and Hospital

Orlando, Florida, United States

Site Status

New Lung Associates, PA; Lung Transplant, Adult Cystic Fibrosis, and the Center for Advanced Lung Diseases, Tampa General Hospital

Tampa, Florida, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

The Cystic Fibrosis Center of Chicago

Glenview, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

University of Kentucky Cystic Fibrosis Clinic

Lexington, Kentucky, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Massachusetts General Hospital Pediatric Cystic Fibrosis Center

Boston, Massachusetts, United States

Site Status

Boston Children's Hospital Cystic Fibrosis Center

Boston, Massachusetts, United States

Site Status

Wayne State University, Harper Hospital, Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Rutgers Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

Hofstra North Shore - Long Island Jewish School of Medicine

New Hyde Park, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Rainbow Babies and Children's Hospital / University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

The Children's Medical Center of Dayton

Dayton, Ohio, United States

Site Status

Santiago Reyes, MD

Oklahoma City, Oklahoma, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor College of Medicine and Texas Children's Hospital

Houston, Texas, United States

Site Status

University of Texas Health Science Center at Tyler

Tyler, Texas, United States

Site Status

University of Utah, Intermountain Cystic Fibrosis Center

Salt Lake City, Utah, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Countries

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United States

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.

Reference Type DERIVED
PMID: 36511181 (View on PubMed)

Other Identifiers

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SAV005-02

Identifier Type: -

Identifier Source: org_study_id

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