Efficacy and Safety Study of AeroVanc for the Treatment of Persistent MRSA Lung Infection in Cystic Fibrosis Patients
Condition: Cystic Fibrosis
MeSH terms: Infections; Cystic Fibrosis; Fibrosis
Intervention: Vancomycin hydrochloride inhalation powder; Placebo inhalation powder
Intervention description: 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.
Intervention MeSH terms: Vancomycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 87.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Cystic Fibrosis; MRSA; Methicillin-resistant Staphylococcus aureus; Lung infection; AeroVanc; Vancomycin

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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.

          2. Able and willing to comply with the protocol, including availability for all scheduled
             study visits.

          3. 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).

          4. Be ≥12 years old at time of ICF/Assent Form signing.

          5. Have sputum culture positive for MRSA at Screening, with at least 10,000 CFUs/mL of
             MRSA.

          6. 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.

          7. Have forced expiratory volume in 1 second (FEV1) ≥30% and ≤100% of predicted that is
             normalized for age, gender, and height at Screening.

          8. 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.

          9. Be able to perform all the techniques necessary to use the AeroVanc inhaler and
             measure lung function.

         10. Be able to produce expectorated sputum samples or be able and willing to undergo
             standardized sputum induction.

         11. Agree not to smoke from Screening through the end of the study.

         12. 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.

         13. 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).

        Exclusion Criteria:

          1. Administration of any investigational drug or device within 28 days prior to
             ICF/Assent Form signing.

          2. 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).

          3. 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.

          4. History of severe cough/bronchospasm upon inhalation of dry powder inhalation product,
             or nebulized vancomycin.

          5. 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).

          6. Oral corticosteroids in doses exceeding 10 mg prednisone per day or 20 mg prednisone
             every other day, or equipotent doses of another corticosteroid.

          7. 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.

          8. An acute upper or lower respiratory infection, or pulmonary exacerbation within 7 days
             prior to Randomization.

          9. Changes in antimicrobial, bronchodilator, anti-inflammatory or corticosteroid
             medications within 7 days prior to ICF/Assent Form signing.

         10. Current daily continuous oxygen supplementation or requirement for more than 2 L/min
             at night.

         11. Changes in physiotherapy technique or schedule within 7 days prior to ICF/Assent Form
             signing.

         12. History of lung or other solid organ transplantation or currently on the list to
             receive lung or other solid organ transplantation.

         13. A chest X-Ray at Screening with abnormalities indicating a significant acute finding
             (eg, pneumothorax, or pleural effusion).

         14. Lactating female or female with a positive pregnancy test result. All women of
             childbearing potential will be tested.

         15. Renal insufficiency, defined as creatinine clearance <50 mL/min using the
             Cockcroft-Gault equation for adults or Schwartz equation in children, at Screening.

         16. Diagnosed with clinically significant hearing loss.

         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 the time of Screening.

         18. Serum hematology or chemistry screening results which in the judgment of the
             Investigator would interfere with completion of the study.

         19. Positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis
             C virus (HCV).

         20. Other findings or medical history at screening that, in the Investigator's opinion,
             would compromise the safety of the patient or the quality of the study data.