Clinical trial: A Study of AeroVanc for the Treatment of MRSA Infection in CF Patients (NCT03181932)

Eligibility criteria:
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 (i.e., 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 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. 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; 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).
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 6 Years old.


Patient description (medical language): A 30-year-old man who is a computer scientist came to the clinic with the lab result stating azoospermia.  The patient is sexually active with his wife and does not use any contraception methods.  They have been trying to conceive for the past year with no success.  The patient has a past medical history of recurrent pneumonia, shortness of breath, and  persistent cough that produces large amounts of thick sputum. The patient had multiple lung infections during childhood. He does not smoke, use illicit drugs or alcohol.  The patient has no history of other medical conditions including allergies or any kind of surgery.  On physical examination, the digits show clubbing.  An ultrasound shows bilateral absence of the vas deferens, and FEV1 was 75% on the respiratory function test.

Patient description (patient's own words): I'm a 30-year-old computer scientist. I did some lab tests that came back quite alarming, stating that I have azoospermia?! I'm sexually active with my wife and we don't use contraception. We've been trying to have a child for the past year. I have a medical history of pneumonia and shortness of breath and regular wet cough. I had several lung infections when I was a kid. That's why I'm very careful and don't smoke, do drugs, or drink. I don't have other medical conditions including allergies or any kind of surgery. The doctor did the clubbing test on my fingers, which was positive. I also did an ultrasound and it showed that I'm missing the tubes that carry sperm around. I also had a 75% for my respiratory function test.

Does the patient match the trial criteria? Entailment