AeroVanc in the Treatment of Methicillin-resistant Staphylococcus Aureus Infection in Patients With Cystic Fibrosis
Condition: MRSA; Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: Vancomycin inhalation powder; Placebo inhalation powder; Vancomycin inhalation powder
Intervention description: 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.; 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.; In the 24-week Period 2, all participants are to be treated with open-label vancomycin inhalation powder.
Intervention MeSH terms: Vancomycin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 188.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        Inclusion criteria

          1. Participants ≥6 years of age at time of informed consent form 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 milliequivalent/L),

               2. Genotype with 2 mutations consistent with CF (i.e., a mutation in each of the
                  cystic fibrosis transmembrane conductance regulator 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 >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)

          5. FEV1 ≥30% and ≤90% of predicted that is normal for age, gender, race, and height,
             using the Global Lung Function Initiative 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; 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, 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. 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.

        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 Burkholderia 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, or
             vancomycin intermediate resistant Staphylococcus aureus, with minimum inhibitory
             concentration ≥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 cystic fibrosis transmembrane conductance
             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. Oxygen saturation <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 of serum aspartate
             aminotransferase or serum alanine aminotransferase, or known cirrhosis at Screening.

         18. Diagnosed with clinically significant hearing loss.

         19. History of positive result for human immunodeficiency virus, hepatitis B virus or
             hepatitis C virus.

         20. Planned hospitalizations for prophylaxis antibiotic treatment within 28 days prior to
             Baseline visit or during the double-blind period (Period 1).