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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03181932
Recruitment Status : Recruiting
First Posted : June 9, 2017
Last Update Posted : May 3, 2018
Information provided by (Responsible Party):
Savara Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
MRSA Cystic Fibrosis Drug: Vancomycin inhalation powder Drug: Placebo inhalation powder Phase 3

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 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 26, 2017
Estimated Primary Completion Date : June 15, 2019
Estimated Study Completion Date : December 15, 2019

Arm Intervention/treatment
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).
Other Name: 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).

Primary Outcome Measures :
  1. The mean absolute change from baseline in FEV1 percent predicted. The endpoint will be analyzed sequentially at Week 4 (end of Cycle 1) and at Week 20 (end of Cycle 3). [ Time Frame: Week 4 and 20 of treatment period ]

Secondary Outcome Measures :
  1. Time to use of another antibiotic medication (oral, IV, and/or inhaled) for pulmonary infection [ Time Frame: Week 20 of treatment period ]
  2. The number of successful response cycles a subject achieves over Period 1 [ Time Frame: Weeks 4, 12, and 20 ]
  3. Relative change from Baseline in FEV1 percent predicted [ Time Frame: Weeks 4 and 20 ]
  4. Change from Baseline in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) scores [ Time Frame: Weeks 4 and 20 ]
  5. Change from Baseline in the Cystic Fibrosis Respiratory Symptom Diary-Chronic Respiratory Symptom Score (CFRSD-CRISS) scores [ Time Frame: Weeks 4 and 20 ]

Other Outcome Measures:
  1. Changes from Baseline in EQ-5D-5L/EQ-5Dy scores [ Time Frame: Weeks 4 and 20 ]
  2. Change from Baseline in MRSA sputum density [ Time Frame: Weeks 4 and 20 ]
  3. Change from Baseline in body weight [ Time Frame: Weeks 8 and 24 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   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:

    1. Positive sweat chloride test (value ≥ 60 mEq/L),
    2. Genotype with 2 mutations consistent with CF (ie, a mutation in each of the cystic fibrosis transmembrane conductance regulator [CFTR] genes).
  3. Positive sputum culture or a throat swab culture for MRSA at Screening.
  4. 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 cultures (sputum or throat swab culture) collected over the previous 1 year must have tested positive for MRSA.
  5. 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.
  6. 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).
  7. 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; male subjects who are non-sterile (ie, male who has not been sterilized by vasectomy for at least 6 months) must be willing to 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).
  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) during the Screening period, 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) during the Screening period, 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 mcg/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 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03181932

Contact: Jessica Jackson 832-231-6283

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Sponsors and Collaborators
Savara Inc.
Principal Investigator: Patrick Flume, MD Medical University of South Carolina

Responsible Party: Savara Inc. Identifier: NCT03181932     History of Changes
Other Study ID Numbers: SAV005-04
First Posted: June 9, 2017    Key Record Dates
Last Update Posted: May 3, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Anti-Bacterial Agents
Anti-Infective Agents