AeroVanc in the Treatment of Methicillin-resistant Staphylococcus Aureus Infection in Patients With Cystic Fibrosis

NCT03181932 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: SAV005-04
• Study Type: interventional
• Target: 188
• Locations: 2 countries
• Sites: 71

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).

Conditions

MRSA; Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted

  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).

  Baseline and Week 4, 12 and 20

Secondary Outcomes (7)

• Frequency of Pulmonary Exacerbations

  Week 20

• Time to First Pulmonary Exacerbation

  Week 20

• Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Scores

  Baseline and Week 4, 12, and 20

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

  Baseline and Week 4, 12 and 20

• Relative Change in FEV1 Percent Predicted

  Baseline and Week 4, 12 and 20

Study Arms (3)

Double-blind vancomycin inhalation powder

EXPERIMENTAL

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.

Drug: Vancomycin inhalation powder

Double-blind placebo inhalation powder

PLACEBO COMPARATOR

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.

Drug: Placebo inhalation powder

Open-label vancomycin inhalation powder

EXPERIMENTAL

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.

Drug: Vancomycin inhalation powder

Interventions

Vancomycin inhalation powder DRUG

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.

Also known as: AeroVanc

Double-blind vancomycin inhalation powder

Placebo inhalation powder DRUG

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.

Double-blind placebo inhalation powder

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants ≥6 years of age at time of informed consent form or assent form signing.
• Confirmed diagnosis of CF, determined by having clinical features consistent with the CF phenotype, plus one of the following:
• Positive sweat chloride test (value ≥60 milliequivalent/L),
• Genotype with 2 mutations consistent with CF (i.e., a mutation in each of the cystic fibrosis transmembrane conductance regulator genes).
• Positive sputum culture or a throat swab culture for MRSA at Screening.
• 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)
• FEV1 ≥30% and ≤90% of predicted that is normal for age, gender, race, and height, using the Global Lung Function Initiative equation.
• 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).
• 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:
• Oral birth control pills administered for at least 1 monthly cycle prior to administration of the study drug.
• 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.
• Intrauterine devices, inserted by a qualified clinician for at least 1 monthly cycle prior to study drug administration.
• 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.
• Hysterectomy or surgical sterilization.

You may not qualify if:

• Use of anti-MRSA treatments prescribed as maintenance therapy (intravenous \[IV\] or inhaled treatment within 28 days; oral treatment within 14 days) prior to the Baseline visit.
• 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.
• 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.
• Inability to tolerate inhaled products.
• First time sputum culture or throat swab culture yielding Burkholderia cepacia, or nontuberculous Mycobacteria in the previous 6 months to Screening.
• History of lung or other solid organ transplantation or currently on the list to receive lung or other solid organ transplantation.
• Resistance to vancomycin at Screening (vancomycin resistant Staphylococcus aureus, or vancomycin intermediate resistant Staphylococcus aureus, with minimum inhibitory concentration ≥8 μg/mL).
• Oral corticosteroids in doses exceeding 10 mg prednisone per day or 20 mg prednisone every other day, or equipotent doses of other corticosteroids.
• 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.
• 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.
• Inability to tolerate inhalation of a short acting beta2 agonist
• Oxygen saturation \<90% at Screening.
• Changes in physiotherapy technique or physiotherapy scheduled within 1 week of the Baseline visit.
• Administration of any investigational drug or device within 4 weeks prior to the Screening visit and during the study
• Female with positive pregnancy test result during Screening, pregnant (or intends to become pregnant), lactating or intends to breastfeed during the study.

Sponsors & Collaborators

• Savara Inc.: lead

Study Sites (71)

Pulmonary Associates of Mobile

Mobile, Alabama, 36608, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Miller Childrens Hospital MemorialCare Health System Pediatric Pulmonology

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of Southern California Keck Medical Center of USC

Los Angeles, California, 90033, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

National Jewish Health Adult Cystic Fibrosis Center

Denver, Colorado, 80206, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida Pediatrics

Gainesville, Florida, 32610, United States

Location

Memorial Healthcare System

Hollywood, Florida, 33021, United States

Location

Nemours Childrens Specialty Care

Jacksonville, Florida, 32207, United States

Location

University of Miami Bachelor Children's Hospital

Miami, Florida, 33136, United States

Location

Central Florida Pulmonary Group

Orlando, Florida, 32803, United States

Location

Arnold Palmer Hospital Pulmonary and Sleep Medical Institute Orlando Health, Inc

Orlando, Florida, 32806, United States

Location

Nemours Children's Hospital

Orlando, Florida, 32827, United States

Location

Nemours Children's Specialty Care

Pensacola, Florida, 32514, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Health Care of Atlanta at Scottish Rite

Atlanta, Georgia, 30342, United States

Location

Augusta Univ Cystic Fibrosis Center

Augusta, Georgia, 30912, United States

Location

Chicago CF Care Specialists

Glenview, Illinois, 60025, United States

Location

NorthSurburban Pulmonary Specialists

Morton Grove, Illinois, 60053, United States

Location

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Department of Pediatrics

Iowa City, Iowa, 52242, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Via Christi Health Systems CF Clinic

Wichita, Kansas, 67214, United States

Location

University of Louisville Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, 40202, United States

Location

Maine Medical Partners Pediatric Specialty Care

Portland, Maine, 04102, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University (HUH)

Detroit, Michigan, 48201, United States

Location

Children's Mercy

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Hospital /Saint Louis University

St Louis, Missouri, 63104, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Rutgers-Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

University of New Mexico Pediatric/Pulmonary

Albuquerque, New Mexico, 87131, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Northwell Health, Div of Pulmonary, Critical Care & Sleep Medicine

New Hyde Park, New York, 11042, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Levine Children's Hospital - Atrium Health

Charlotte, North Carolina, 28203, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University Hospital Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

The Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

Location

Toledo Children's Hospital CF Center

Toledo, Ohio, 43606, United States

Location

University of Oklahoma Health Science Center - Pediatric Pulmonary & CF Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Penn State Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMCU

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

Sanford Childrens Specialty Clinic

Sioux Falls, South Dakota, 57105, United States

Location

UTHSC Lebonheur Children's Hospital

Memphis, Tennessee, 38103, United States

Location

Austin Children's Chest Associates

Austin, Texas, 78723, United States

Location

Children's Medical Center Cystic Fibrosis Clinic

Dallas, Texas, 75235, United States

Location

Cook Children Medical Center

Fort Worth, Texas, 76104, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

The University of Texas Health Science Center at Tyler

Tyler, Texas, 75708, United States

Location

University of Utah Health Sciences Center

Salt Lake City, Utah, 84132, United States

Location

University Vermont Medical Center Vermont Lung Center

Colchester, Vermont, 05446, United States

Location

University of Virginia Health System, Cystic Fibrosis Center

Charlottesville, Virginia, 22908, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Providence Medical Research Center

Spokane, Washington, 99204, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

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

Limitations and Caveats

A total of 200 participants were to be randomized. Consequent to the outbreak of COVID-19, the recruitment was stopped prematurely when 188 participants had been randomized. The CFQ-R and CFRSD-CRISS were administered every two weeks using a hand-held e-Diary. The e-Diary had not been activated at the baseline visit for 39 participants. For these participants, missing baseline measurements were imputed with the population median baseline value for inferential analyses.

Results Point of Contact

• Title: Raymond D Pratt, Chief Medical Officer
• Organization: Savara Inc

ray.pratt@savarapharma.com

+1 512 784 8757

Study Officials

• Patrick Flume, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: June 1, 2017
• First Posted: June 9, 2017
• Study Start: September 20, 2017
• Primary Completion: July 28, 2020
• Study Completion: January 15, 2021
• Last Updated: December 16, 2022
• Results First Posted: November 5, 2021

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (69); CA (2)