Efficacy and Safety Study of AeroVanc for the Treatment of Persistent MRSA Lung Infection in Cystic Fibrosis Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01746095
• Date of registration: 06/12/2012
• Prospective Registration: Yes
• Primary sponsor: Savara Inc.
• Public title: Efficacy and Safety Study of AeroVanc for the Treatment of Persistent MRSA Lung Infection in Cystic Fibrosis Patients
• Scientific title: A Phase 2, Randomized, Double Blind, Placebo-controlled Study of AeroVanc for the Treatment of Persistent Methicillin-resistant Staphylococcus Aureus Lung Infection in Cystic Fibrosis Patients
• Date of first enrolment: March 2013
• Target sample size: 87
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01746095
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Elliott Dasenbrook, M.D., MHS
• Affiliation: Case Western Reserve University School of Medicine and Rainbow Babies and Children's Hospital

Key inclusion & exclusion 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.



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Vancomycin hydrochloride inhalation powder

Drug: Placebo inhalation powder

Primary Outcome(s)

Change From Baseline in MRSA Sputum Density. [Time Frame: Day 29 of treatment period]

Secondary Outcome(s)

Time From Start of Dosing to Exacerbation of Signs/Symptoms (Fuchs Criteria). [Time Frame: Entire study: Day 1 of treatment period through 8 week post-treatment follow up visit]

Change From Baseline in Cystic Fibrosis Respiratory Symptom Diary (CFRSD-CRISS) Scores [Time Frame: Day 29 of treatment period]

Change From Baseline in Blood Neutrophils [Time Frame: Day 29 of the dosing period]

Change From Baseline in MRSA Sputum Density. [Time Frame: Day 8 of treatment period]

Change From Baseline in MRSA Sputum Density. [Time Frame: Day 15 of treatment period]

Time From Start of Dosing to First Administration of Other Antimicrobial Medications (Oral, Intravenous and/or Inhaled) Due to Respiratory Symptoms. [Time Frame: Entire study: Day 1 of treatment period through 8 week post-treatment follow up visit]

Change From Baseline in FEV1 [Time Frame: Day 29 of treatment period]

Change From Baseline in FVC [Time Frame: Day 29 of treatment period]

Change From Baseline in High Sensitivity CRP [Time Frame: Day 29 of the dosing period]

Secondary ID(s)

SAV005-02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Cystic Fibrosis Foundation

Synteract, Inc.

Results

• Results available: Yes
• Date Posted: 13/01/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01746095