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

NCT01746095 | Completed Phase 2 Results DMC

• 1 other identifier: SAV005-02
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 38

Brief Summary

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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; MRSA; Methicillin-resistant Staphylococcus aureus; Lung infection; AeroVanc; Vancomycin

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in MRSA Sputum Density.

  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.

  Day 29 of treatment period

Secondary Outcomes (9)

• Change From Baseline in MRSA Sputum Density.

  Day 8 of treatment period

• Change From Baseline in MRSA Sputum Density.

  Day 15 of treatment period

• Change From Baseline in FEV1

  Day 29 of treatment period

• Change From Baseline in FVC

  Day 29 of treatment period

• Change From Baseline in Cystic Fibrosis Respiratory Symptom Diary (CFRSD-CRISS) Scores

  Day 29 of treatment period

Study Arms (2)

Vancomycin hydrochloride inhalation powder

EXPERIMENTAL

32 or 64 mg twice daily (BID)

Drug: Vancomycin hydrochloride inhalation powder

Placebo inhalation powder

PLACEBO COMPARATOR

Matching placebo inhalation powder BID

Drug: Placebo inhalation powder

Interventions

Vancomycin hydrochloride inhalation powder 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.

Also known as: AeroVanc

Vancomycin hydrochloride inhalation powder

Placebo inhalation powder DRUG

Placebo inhalation powder

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Able and willing to comply with the protocol, including availability for all scheduled study visits.
• 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).
• Be ≥12 years old at time of ICF/Assent Form signing.
• Have sputum culture positive for MRSA at Screening, with at least 10,000 CFUs/mL of MRSA.
• 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.
• Have forced expiratory volume in 1 second (FEV1) ≥30% and ≤100% of predicted that is normalized for age, gender, and height at Screening.
• 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.
• Be able to perform all the techniques necessary to use the AeroVanc inhaler and measure lung function.
• Be able to produce expectorated sputum samples or be able and willing to undergo standardized sputum induction.
• Agree not to smoke from Screening through the end of the study.
• 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.
• 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).

You may not qualify if:

• Administration of any investigational drug or device within 28 days prior to ICF/Assent Form signing.
• 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).
• 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.
• History of severe cough/bronchospasm upon inhalation of dry powder inhalation product, or nebulized vancomycin.
• 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).
• Oral corticosteroids in doses exceeding 10 mg prednisone per day or 20 mg prednisone every other day, or equipotent doses of another corticosteroid.
• 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.
• An acute upper or lower respiratory infection, or pulmonary exacerbation within 7 days prior to Randomization.
• Changes in antimicrobial, bronchodilator, anti-inflammatory or corticosteroid medications within 7 days prior to ICF/Assent Form signing.
• Current daily continuous oxygen supplementation or requirement for more than 2 L/min at night.
• Changes in physiotherapy technique or schedule within 7 days prior to ICF/Assent Form signing.
• History of lung or other solid organ transplantation or currently on the list to receive lung or other solid organ transplantation.
• A chest X-Ray at Screening with abnormalities indicating a significant acute finding (eg, pneumothorax, or pleural effusion).
• Lactating female or female with a positive pregnancy test result. All women of childbearing potential will be tested.
• Renal insufficiency, defined as creatinine clearance \<50 mL/min using the Cockcroft-Gault equation for adults or Schwartz equation in children, at Screening.

Sponsors & Collaborators

• Savara Inc.: lead
• Synteract, Inc.: collaborator
• Cystic Fibrosis Foundation: collaborator

Study Sites (38)

Pulmonary Associates of Mobile

Mobile, Alabama, 36608, United States

Location

University of Arkansas for Medical Science

Little Rock, Arkansas, 72205, United States

Location

Children's Hospital Los Angeles, Division of Pediatric Pulmonology

Los Angeles, California, 90027, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

Location

University of Miami - Miller School of Medicine

Miami, Florida, 33136, United States

Location

Central Florida Pulmonary Group

Orlando, Florida, 32803, United States

Location

Nemours Children's Clinic and Hospital

Orlando, Florida, 32806, United States

Location

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

Tampa, Florida, 33606, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

The Cystic Fibrosis Center of Chicago

Glenview, Illinois, 60025, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky Cystic Fibrosis Clinic

Lexington, Kentucky, 40536, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Massachusetts General Hospital Pediatric Cystic Fibrosis Center

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital Cystic Fibrosis Center

Boston, Massachusetts, 02115, United States

Location

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

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

Hofstra North Shore - Long Island Jewish School of Medicine

New Hyde Park, New York, 11040, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

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

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

The Children's Medical Center of Dayton

Dayton, Ohio, 45404, United States

Location

Santiago Reyes, MD

Oklahoma City, Oklahoma, 73112, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine and Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at Tyler

Tyler, Texas, 75708, United States

Location

University of Utah, Intermountain Cystic Fibrosis Center

Salt Lake City, Utah, 84132, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• 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.

  PMID: 36511181 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Head of Clinical Development
• Organization: Savara Inc.

info@savarapharma.com

+45 7930 1414

Study Officials

• Elliott Dasenbrook, M.D., MHS

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2012
• First Posted: December 10, 2012
• Study Start: March 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: January 13, 2020
• Results First Posted: January 13, 2020

Record last verified: 2019-12

Locations

US (38)