A Study of AeroVanc for the Treatment of MRSA Infection in CF Patients

Purpose

This study is a multi-center, randomized phase III study to evaluate the clinical effectiveness of AeroVanc in persistent MRSA in patients with Cystic Fibrosis.

Conditions

  • MRSA
  • Cystic Fibrosis

Eligibility

Eligible Ages
Over 6 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Subjects ≥ 6 years of age at time of Informed Consent Form (ICF) or Assent Form signing.
  2. Confirmed diagnosis of CF, determined by having clinical features consistent with the CF phenotype, plus one of the following:
  3. Positive sweat chloride test (value ≥ 60 mEq/L),
  4. Genotype with 2 mutations consistent with CF (i.e., a mutation in each of the cystic fibrosis transmembrane conductance regulator [CFTR] genes).
  5. Positive sputum culture or a throat swab culture for MRSA at Screening.
  6. 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 more than 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)
  7. Forced expiratory volume in 1 second (FEV1) ≥ 30% and ≤ 90% of predicted that is normal for age, gender, race, and height, using the Global Lung Function Initiative (GLI) equation.
  8. 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).
  9. 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:

1. Oral birth control pills administered for at least 1 monthly cycle prior to administration of the study drug.

2. 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.

3. Intrauterine devices (IUDs), inserted by a qualified clinician for at least 1 monthly cycle prior to study drug administration.

4. 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.

5. Hysterectomy or surgical sterilization.

6. Abstinence.

7. 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.

8. 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.

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

10. Subjects with a 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.

Exclusion Criteria

  1. 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.
  2. 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.
  3. 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. Inability to tolerate inhaled products.
  5. First time sputum culture or throat swab culture yielding B. cepacia, or nontuberculous Mycobacteria in the previous 6 months to Screening.
  6. History of lung or other solid organ transplantation or currently on the list to receive lung or other solid organ transplantation.
  7. Resistance to vancomycin at Screening (vancomycin resistant Staphylococcus aureus [VRSA], or vancomycin intermediate resistant Staphylococcus aureus [VISA], with minimum inhibitory concentration [MIC] ≥ 8 μg/mL).
  8. Oral corticosteroids in doses exceeding 10 mg prednisone per day or 20 mg prednisone every other day, or equipotent doses of other corticosteroids.
  9. Changes in antimicrobial, bronchodilator, anti-inflammatory or corticosteroid medications within 14 days, or changes in CFTR modulators within 28 days, prior to the Baseline visit.
  10. 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.
  11. Inability to tolerate inhalation of a short acting beta2 agonist
  12. SpO2 <90% at Screening.
  13. Changes in physiotherapy technique or physiotherapy scheduled within 1 week of the Baseline visit.
  14. Administration of any investigational drug or device within 4 weeks prior to the Screening visit and during the study
  15. Female with positive pregnancy test result during Screening, pregnant (or intends to become pregnant), lactating or intends to breastfeed during the study.
  16. 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.
  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 Screening.
  18. Diagnosed with clinically significant hearing loss.
  19. History of positive result for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
  20. Planned hospitalizations for prophylaxis antibiotic treatment within 28 days prior to Baseline visit or during the double-blind period (Period 1).

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Vancomycin inhalation powder
30 mg twice daily (BID)
  • Drug: Vancomycin inhalation powder
    There will be 200 patients treated with Vancomycin inhalation powder or placebo (1:1 active to placebo). 150 subjects ≤21 years old, 50 subjects >21 years old.
    Other names:
    • AeroVanc
Placebo Comparator
Placebo inhalation powder
Matching placebo inhaled twice daily (BID)
  • Drug: Placebo inhalation powder
    There will be 200 patients treated with Vancomycin inhalation powder or placebo (1:1 active to placebo). 150 subjects ≤21 years old, 50 subjects >21 years old.

Recruiting Locations

Pulmonary Associates of Mobile
Mobile, Alabama 36608
Contact:
Liz Knight
251-631-3023
eknight@lungmds.com

Phoenix Children's Hospital
Phoenix, Arizona 85016
Contact:
Natalia Argel
602-933-0343
Nargel@phoenixchildrens.com

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
Contact:
Kathleen Hicks
501-686-5527
hickskathleent@uams.edu

Miller Childrens Hospital MemorialCare Health System Pediatric Pulmonology
Long Beach, California 90806
Contact:
Candice Evans
562-933-5607
cevans@memorialcare.org

Children's Hospital Los Angeles
Los Angeles, California 90027
Contact:
Elizabeth Rowan
323-361-2972
erowan@chla.usc.edu

University of Southern California Keck Medical Center of USC
Los Angeles, California 90033
Contact:
Lynn Fukushima
323-409-5383
Lynn.fukushima@med.usc.edu

UC Davis Medical Center
Sacramento, California 95817
Contact:
Brandt Robinson
916-734-8686
brrobinson@ucdavis.edu

Children's Hospital Colorado
Aurora, Colorado 80045
Contact:
Mary Cross
720-777-4645
Mary.Cross@childrenscolorado.org

National Jewish Health Adult Cystic Fibrosis Center
Denver, Colorado 80206
Contact:
Connie St Clair
303-270-2827
stclair@njhealth.org

University of Florida Pediatrics
Gainesville, Florida 32610
Contact:
Dawn Baker
352-273-5417
bakerdj@peds.ufl.edu

Memorial Healthcare System
Hollywood, Florida 33021
Contact:
Norma Jean Barton
954-265-4466
nbarton@mhs.net

Nemours Childrens Specialty Care
Jacksonville, Florida 32207
Contact:
Betty DeLuca
904-697-3804
Elizabeth.deluca@nemours.org

University of Miami Bachelor Children's Hospital
Miami, Florida 33136
Contact:
Alejandra Weisman
305-243-1425
a.weisman1@miami.edu

Central Florida Pulmonary Group
Orlando, Florida 32803
Contact:
Kenneth Kesser
407-841-1100
bkesser@cfpulmonary.com

Arnold Palmer Hospital Pulmonary and Sleep Medical Institute Orlando Health, Inc
Orlando, Florida 32806
Contact:
Yajira Beltram
321-841-7619
Yajira.Beltran@orlandohealth.com

Nemours Children's Hospital
Orlando, Florida 32827
Contact:
Germaine Wezel
407-650-7964
Germaine.wezel@nemours.org

Johns Hopkins All Children's Hospital
Saint Petersburg, Florida 33701
Contact:
Diana Hodge
727-767-6881
Dhodge6@jhmi.edu

Children's Health Care of Atlanta at Scottish Rite
Atlanta, Georgia 30342
Contact:
Terri Eubanks
404-785-3225
terri.eubanks@choa.org

Augusta Univ Cystic Fibrosis Center
Augusta, Georgia 30912
Contact:
Heidi Stapp
706-721-7699
hstapp@augusta.edu

Chicago CF Care Specialists
Glenview, Illinois 60025
Contact:
Katherine McKeown
847-998-3434
katie@wecare4lungs.com

NorthSurburban Pulmonary Specialists
Morton Grove, Illinois 60053
Contact:
Suellen Moen
847-738-7334
suellen.moen@advocatehealth.com

Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana 46202
Contact:
Lisa France
317-944-3380
lfrance@iupui.edu

University of Iowa Department of Pediatrics
Iowa City, Iowa 52242
Contact:
Tyler Farber
319-384-7546
tyler-farber@uiowa.edu

University of Kansas
Kansas City, Kansas 66160
Contact:
Lawrence Scott
913-588-4020
lscott2@kumc.edu

Via Christi Health Systems CF Clinic
Wichita, Kansas 67214
Contact:
Lisa Aragon
316-268-6009
Lisa.Aragon@ascension.org

University of Louisville Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky 40202
Contact:
Molly Harper, BA, CCRC
502-629-4695
mrharp02@louisville.edu

Maine Medical Partners Pediatric Specialty Care
Portland, Maine 04102
Contact:
Carrie Milliard
207-662-6712
millic@mmc.org

Boston Children's Hospital
Boston, Massachusetts 02115
Contact:
Elizabeth Carpino
617-355-2446
Elizabeth.carpino@childrens.harvard.edu

University of Michigan Health System
Ann Arbor, Michigan 48109
Contact:
Dawn Kruse
734-615-3266
dmkruse@med.umich.edu

Wayne State University (HUH)
Detroit, Michigan 48201
Contact:
Aleah Hall
313-745-4737
AHall@dmc.org

Children's Health Care
Minneapolis, Minnesota 55404
Contact:
Anne Mills
612-813-7756
Anne.mills@childrensmn.org

Children's Mercy
Kansas City, Missouri 64108
Contact:
April Williams
816-458-4116
alwilliams1@cmh.edu

Cardinal Glennon Children's Hospital /Saint Louis University
Saint Louis, Missouri 63104
Contact:
Freda Branch
314-678-5457
freda.branch@health.slu.edu

Washington University
Saint Louis, Missouri 63110
Contact:
Irma Bauer
314-747-2940
irmabauer@wustl.edu

University of Nebraska Medical Center
Omaha, Nebraska 68198
Contact:
Toni Blazek
402-708-2785
tblazek@unmc.edu

Morristown Medical Center
Morristown, New Jersey 07960
Contact:
Deb Connolly
973-971-5138
nancy.martinez@atlantichealth.org

Rutgers-Robert Wood Johnson Medical School
New Brunswick, New Jersey 08901
Contact:
Fei Chen
732-235-5108
chenf2@rwjms.rutgers.edu

University of New Mexico Pediatric/Pulmonary
Albuquerque, New Mexico 87131
Contact:
Olivia Nunez
505-272-9898
odnunez@salud.unm.edu

Albany Medical College
Albany, New York 12208
Contact:
Anne Denero
518-262-7851
deneroa@mail.amc.edu

Northwell Health, Div of Pulmonary, Critical Care & Sleep Medicine
New Hyde Park, New York 11042
Contact:
Stacy Jackson
516-465-5400
sjackson13@northwell.edu

Columbia University Medical Center
New York, New York 10032
Contact:
Amanda Kramer
212-305-4675
ark2187@columbia.edu

Duke University Medical Center
Durham, North Carolina 27710
Contact:
Heidi Tiedge
919-681-7391
heidi.tiedge@duke.edu

Wake Forest School of Medicine
Winston-Salem, North Carolina 27157
Contact:
Kathryn Kennedy
336-713-8559
klkenned@wakehealth.edu

Akron Children's Hospital
Akron, Ohio 44308
Contact:
Brenda Bourne
330-543-3510
bbourne@akronchildrens.org

Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229
Contact:
Sharon Kadon
513-803-4325
Sharon.Kadon@cchmc.org

University Hospital Cleveland Medical Center
Cleveland, Ohio 44106
Contact:
Brittany Hirth
216-844-8270
Brittany.Hirth@uhhospitals.org

The Research Institute at Nationwide Children's Hospital
Columbus, Ohio 43205
Contact:
Laura Raterman
614-722-4758
laura.raterman@nationwidechildrens.org

Dayton Children's Hospital
Dayton, Ohio 45404
Contact:
Sandy Bartosik
937-641-4004
bartosiks@childrensdayton.org

Toledo Children's Hospital CF Center
Toledo, Ohio 43606
Contact:
Kelly Hoot
419-291-4630
Kelly.Hoot@promedica.org

University of Oklahoma Health Science Center - Pediatric Pulmonary & CF Center
Oklahoma City, Oklahoma 73104
Contact:
Ashley Sanders
405-271-8001
ashley-sanders@ouhsc.edu

Dr. Santiago Reyes, P.C.
Oklahoma City, Oklahoma 73112
Contact:
Teresa Orf
405-945-4495
teresaorf@yahoo.com

Oregon Health and Science University
Portland, Oregon 97239
Contact:
Jenna Bucher
503-494-6180
bucherj@ohsu.edu

Penn State Children's Hospital
Hershey, Pennsylvania 17033
Contact:
Diane Kitch
717-531-5646
dkitch@hmc.psu.edu

University of Pennsylvania
Philadelphia, Pennsylvania 19104
Contact:
Victoria Fleck
215-662-3115
Victoria.fleck@uphs.upenn.edu

Children's Hospital of Pittsburgh of UPMCU
Pittsburgh, Pennsylvania 15224
Contact:
Rose Lanzo
412-692-5872
rose.lanzo@chp.edu

Medical University of South Carolina (MUSC)
Charleston, South Carolina 29425
Contact:
Abbi Reed
843-792-1820
reedab@musc.edu

Sanford Childrens Specialty Clinic
Sioux Falls, South Dakota 57105

UTHSC Lebonheur Children's Hospital
Memphis, Tennessee 38103
Contact:
Cathy Horobetz
901-287-6483
chorobet@uthsc.edu

Austin Children's Chest Associates
Austin, Texas 78723
Contact:
Colleen Millian
512-380-9200
CaMillian@ascension.org

Children's Medical Center Cystic Fibrosis Clinic
Dallas, Texas 75235
Contact:
Daniyal Kamal
214-456-5489
Daniyal.Kamal@childrens.com

Cook Children Medical Center
Fort Worth, Texas 76104
Contact:
Heather Urbanek
682-885-1244
Heather.urbanek@cookchildrens.org

Texas Children's Hospital
Houston, Texas 77030
Contact:
Ellen Edwards
832-822-4772
exedward@texaschildrens.org

University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
Contact:
Robin Tragus
210-567-5262
tragus@uthscsa.edu

UT Health Science Center at San Antonio
San Antonio, Texas 78229
Contact:
Robin Tragus
210-567-5262
tragus@uthscsa.edu

The University of Texas Health Science Center at Tyler
Tyler, Texas 75708
Contact:
Lilly Dohanich
903-877-5435
Elizabeth.garza@uthct.edu

University of Utah Health Sciences Center
Salt Lake City, Utah 84132
Contact:
Jane Vroom
801-587-7458
Jane.vroom@hsc.utah.edu

University Vermont Medical Center Vermont Lung Center
Colchester, Vermont 05446
Contact:
Julie Sweet
802-847-7958
Julie.sweet@uvmhealth.org

University of Virginia Health System, Cystic Fibrosis Center
Charlottesville, Virginia 22908
Contact:
Christie L. Aderholt, RN, BSN
434-297-7773
cla6e@virginia.edu

Childrens Hospital of The King's Daughters
Norfolk, Virginia 23507
Contact:
Jennifer Parrot
757-668-8244
Jennifer.Parrott@chkd.org

Seattle Children's Hospital
Seattle, Washington 98105
Contact:
Sharon McNamara
206-987-3921
sharon.mcnamara@seattlechildrens.org

West Virginia University
Morgantown, West Virginia 26506
Contact:
Tammy Clark, RN, BSN
304-293-5264
tclark@hsc.wvu.edu

Children's Hospital of Wisconsin
Milwaukee, Wisconsin 53226
Contact:
Theresa Kump
414-337-7144
tkump@mcw.edu

More Details

NCT ID
NCT03181932
Status
Recruiting
Sponsor
Savara Inc.

Study Contact

Jessica Jackson
832-231-6283
jessica.jackson@savarapharma.com

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 Methicillin resistant Staphylococcus aureus (MRSA) lung infection in patients diagnosed with cystic fibrosis (CF). After the Screening period to confirm study eligibility, subjects will be 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, subjects will 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.

Subjects on a 28-day cyclical on/off anti-Pseudomonal antibiotic regimen will enter the Screening period at a time such that the Baseline visit coincides with the end of their anti-Pseudomonas antibiotic cycle. Study drug will thereby be administered during the off-cycle, and subjects can then resume anti-Pseudomonal therapy during the 28-day observation period. Subjects continuing alternating anti-Pseudomonal therapy can continue their treatment during the study drug administration, and observation period.

The primary and secondary analyses will be conducted in subjects ≤21 years old. Subjects >21 years old will be analyzed separately as a supportive analysis.