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MRSAPhase 3NCT03181932

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

A Phase 3 study testing Vancomycin inhalation powder in people with MRSA and Cystic Fibrosis, run by Savara Inc. at 71 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 6 years and older
Conditions the study is for
MRSA, Cystic Fibrosis
What is being tested?
Vancomycin inhalation powder
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
188 participants
Where
71 sitesin 2 countries
Study dates
20 Sep 2017to 15 Jan 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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)
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  • 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.
  • Abstinence.
  • 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.
  • 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.
  • Agree not to smoke during any part of the clinical trial (Screening visit through end of study).
  • 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.

Who cannot join

  • 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.
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  • 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.
  • 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.
  • Abnormal liver function, defined as ≥4x upper limit of normal of serum aspartate aminotransferase or serum alanine aminotransferase, or known cirrhosis at Screening.
  • Diagnosed with clinically significant hearing loss.
  • History of positive result for human immunodeficiency virus, hepatitis B virus or hepatitis C virus.
  • Planned hospitalizations for prophylaxis antibiotic treatment within 28 days prior to Baseline visit or during the double-blind period (Period 1).

Trial locations and contacts

71 sites in 2 countries.

71 sites in 2 countries

United States69 sites

  • Albany Medical College

    Albany, New York, 12208

  • University of New Mexico Pediatric/Pulmonary

    Albuquerque, New Mexico, 87131

  • University of Michigan Health System

    Ann Arbor, Michigan, 48109

  • Children's Health Care of Atlanta at Scottish Rite

    Atlanta, Georgia, 30342

  • Augusta Univ Cystic Fibrosis Center

    Augusta, Georgia, 30912

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Austin Children's Chest Associates

    Austin, Texas, 78723

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • Medical University of South Carolina (MUSC)

    Charleston, South Carolina, 29425

  • Levine Children's Hospital - Atrium Health

    Charlotte, North Carolina, 28203

  • University of Virginia Health System, Cystic Fibrosis Center

    Charlottesville, Virginia, 22908

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • University Hospital Cleveland Medical Center

    Cleveland, Ohio, 44106

  • University Vermont Medical Center Vermont Lung Center

    Colchester, Vermont, 05446

  • The Research Institute at Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Children's Medical Center Cystic Fibrosis Clinic

    Dallas, Texas, 75235

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • National Jewish Health Adult Cystic Fibrosis Center

    Denver, Colorado, 80206

  • Wayne State University (HUH)

    Detroit, Michigan, 48201

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Cook Children Medical Center

    Fort Worth, Texas, 76104

  • University of Florida Pediatrics

    Gainesville, Florida, 32610

  • Chicago CF Care Specialists

    Glenview, Illinois, 60025

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033

  • Memorial Healthcare System

    Hollywood, Florida, 33021

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Riley Hospital for Children at Indiana University Health

    Indianapolis, Indiana, 46202

  • University of Iowa Department of Pediatrics

    Iowa City, Iowa, 52242

  • Nemours Childrens Specialty Care

    Jacksonville, Florida, 32207

  • University of Kansas

    Kansas City, Kansas, 66160

  • Children's Mercy

    Kansas City, Missouri, 64108

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Miller Childrens Hospital MemorialCare Health System Pediatric Pulmonology

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • University of Southern California Keck Medical Center of USC

    Los Angeles, California, 90033

  • University of Louisville Kosair Charities Pediatric Clinical Research Unit

    Louisville, Kentucky, 40202

  • UTHSC Lebonheur Children's Hospital

    Memphis, Tennessee, 38103

  • University of Miami Bachelor Children's Hospital

    Miami, Florida, 33136

  • Pulmonary Associates of Mobile

    Mobile, Alabama, 36608

  • West Virginia University

    Morgantown, West Virginia, 26506

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • NorthSurburban Pulmonary Specialists

    Morton Grove, Illinois, 60053

  • Rutgers-Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08901

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

    New Hyde Park, New York, 11042

  • Columbia University Medical Center

    New York, New York, 10032

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

    Oklahoma City, Oklahoma, 73104

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Central Florida Pulmonary Group

    Orlando, Florida, 32803

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

    Orlando, Florida, 32806

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Nemours Children's Specialty Care

    Pensacola, Florida, 32514

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

  • Children's Hospital of Pittsburgh of UPMCU

    Pittsburgh, Pennsylvania, 15224

  • Maine Medical Partners Pediatric Specialty Care

    Portland, Maine, 04102

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • UC Davis Medical Center

    Sacramento, California, 95817

  • University of Utah Health Sciences Center

    Salt Lake City, Utah, 84132

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Sanford Childrens Specialty Clinic

    Sioux Falls, South Dakota, 57105

  • Providence Medical Research Center

    Spokane, Washington, 99204

  • Cardinal Glennon Children's Hospital /Saint Louis University

    St Louis, Missouri, 63104

  • Washington University

    St Louis, Missouri, 63110

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • Toledo Children's Hospital CF Center

    Toledo, Ohio, 43606

  • The University of Texas Health Science Center at Tyler

    Tyler, Texas, 75708

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Via Christi Health Systems CF Clinic

    Wichita, Kansas, 67214

  • Wake Forest School of Medicine

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada2 sites

  • The Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

Other trials in Canada

About this study

Official title: A Phase III, Randomized, Double-blind, Placebo-controlled Study of AeroVanc for the Treatment of Persistent Methicillin-resistant Staphylococcus Aureus Lung Infection in Cystic Fibrosis Patients

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).

Read the detailed description

This is a phase III, 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 patients diagnosed with CF. After the Screening period to confirm study eligibility, participants are randomly assigned in a blinded fashion to receive either AeroVanc 30 mg twice daily (BID), or placebo BID (1:1 active to placebo) by inhalation for 24 weeks or 3 dosing cycles (Period 1). Upon completion of Period 1, participants receive open-label AeroVanc 30 mg BID for an additional 24 weeks or 3 dosing cycles (Period 2), to evaluate long-term safety of AeroVanc. A dosing cycle is defined as 28 days of treatment followed by 28 days of observation.

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.

Being tested
Vancomycin inhalation powder, Placebo inhalation powder
Medical subject headings
Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vancomycin inhalation powderDrug

    Also called AeroVanc

    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 powderDrug

    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 powderDrug

    Also called AeroVanc

    In the 24-week Period 2, all participants are to be treated with open-label vancomycin inhalation powder.

Study groups in NCT03181932
Study groupRoleWhat they receive
Double-blind vancomycin inhalation powderExperimentalVancomycin 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.
Receives: Drug: Vancomycin inhalation powder
Double-blind placebo inhalation powderPlacebo comparatorMatching 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.
Receives: Drug: Placebo inhalation powder
Open-label vancomycin inhalation powderExperimentalIn 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.
Receives: Drug: Vancomycin inhalation powder

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Baseline and Week 4, 12 and 20

Secondary outcomes (7)

  1. Frequency of Pulmonary Exacerbations

    The number of pulmonary exacerbations during Period 1 adjusted for the length of follow-up.

    Measured: Week 20

  2. Time to First Pulmonary Exacerbation

    Time to first pulmonary exacerbation requiring use of another antibiotic medication (oral, IV, and/or inhaled). The Outcome Measure Data presented are the median percentiles and 95% confidence intervals from Kaplan-Meier estimates.

    Measured: Week 20

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

    The CFQ-R was administered every two weeks using a hand-held e-Diary. CFQ-R scores range between 0 and 100, where higher scores indicate a better outcome. The CFQ-R measures functioning in a variety of domains, including Physical Functioning, Vitality, Health Perceptions, Respiratory Symptoms, Treatment Burden, Role Functioning, Emotional Functioning and Social Functioning. The Outcome Measure Data presented are the Respiratory Symptoms Scores.

    Measured: Baseline and Week 4, 12, and 20

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

    The CFRSD-CRISS was administered every two weeks using a hand-held e-Diary. Scores range between 0 and 100, where higher scores indicate a worse outcome.

    Measured: Baseline and Week 4, 12 and 20

  5. Relative Change in FEV1 Percent Predicted

    The mean relative change from Baseline in FEV1 percent predicted

    Measured: Baseline and Week 4, 12 and 20

  6. Number of Successful Response Cycles

    The number of successful response cycles a participant achieves over Period 1. A response in a cycle is defined by at least a 5 % relative improvement in FEV1 percent predicted at the end of each the respective cycle.

    Measured: Week 20

  7. Area Under the FEV1-time Profile

    The mean treatment difference in FEV1 across all post-baseline visits

    Measured: Week 20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jun 2017
  2. Study start20 Sep 2017
  3. Primary completion28 Jul 2020
  4. Study completion15 Jan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
188 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03181932
Sponsor's protocol ID
SAV005-04
Status last verified
Dec 2022
First submitted
1 Jun 2017
Last updated
16 Dec 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36511181

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vancomycin inhalation powder in people with MRSA and Cystic Fibrosis, run by Savara Inc. at 71 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 71 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted (time frame: Baseline and Week 4, 12 and 20). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03181932, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2022.

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