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Efficacy and Safety Study of AeroVanc for the Treatment of Persistent MRSA Lung Infection in Cystic Fibrosis 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01746095
Recruitment Status : Completed
First Posted : December 10, 2012
Results First Posted : January 13, 2020
Last Update Posted : January 13, 2020
Sponsor:
Collaborators:
Synteract, Inc.
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Savara Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: Vancomycin hydrochloride inhalation powder
Drug: Placebo inhalation powder
Enrollment 87
Recruitment Details  
Pre-assignment Details  
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description Vancomycin hydrochloride inhalation powder 32 mg BID Placebo inhalation powder BID Vancomycin hydrochloride inhalation powder 64 mg BID Placebo inhalation powder BID
Period Title: Overall Study
Started 20 20 24 23
Completed 16 16 11 15
Not Completed 4 4 13 8
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg Total
Hide Arm/Group Description Vancomycin hydrochloride inhalation powder 32 mg BID Placebo inhalation powder BID Vancomycin hydrochloride inhalation powder 64 mg BID Placebo inhalation powder BID Total of all reporting groups
Overall Number of Baseline Participants 20 20 24 23 87
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 24 participants 23 participants 87 participants
<=18 years
7
  35.0%
6
  30.0%
4
  16.7%
4
  17.4%
21
  24.1%
Between 18 and 65 years
13
  65.0%
14
  70.0%
20
  83.3%
19
  82.6%
66
  75.9%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 24 participants 23 participants 87 participants
Female
13
  65.0%
9
  45.0%
9
  37.5%
8
  34.8%
39
  44.8%
Male
7
  35.0%
11
  55.0%
15
  62.5%
15
  65.2%
48
  55.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants 20 participants 24 participants 23 participants 87 participants
20 20 24 23 87
1.Primary Outcome
Title Change From Baseline in MRSA Sputum Density.
Hide Description Change from Baseline at Day 29 of the dosing period (start of AeroVanc/Placebo administration is considered Day 1 of the dosing period) in the number of MRSA colony forming units (CFU) in sputum culture.
Time Frame Day 29 of treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population, which included all randomized patients who received any amount of study drug and had at least one scheduled post baseline measurement.
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description:
Vancomycin hydrochloride inhalation powder 32 mg BID
Placebo inhalation powder BID
Vancomycin hydrochloride inhalation powder 64 mg BID
Placebo inhalation powder BID
Overall Number of Participants Analyzed 17 17 15 22
Least Squares Mean (Standard Error)
Unit of Measure: Log10 CFU/mL
-0.25  (0.181) -0.30  (0.182) -0.63  (0.232) 0.16  (0.201)
2.Secondary Outcome
Title Change From Baseline in MRSA Sputum Density.
Hide Description [Not Specified]
Time Frame Day 8 of treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population, which included all randomized patients who received any amount of study drug and had at least one scheduled post baseline measurement.
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description:
Vancomycin hydrochloride inhalation powder 32 mg BID
Placebo inhalation powder BID
Vancomycin hydrochloride inhalation powder 64 mg BID
Placebo inhalation powder BID
Overall Number of Participants Analyzed 20 17 24 22
Least Squares Mean (Standard Error)
Unit of Measure: Log10 CFU/mL
-0.27  (0.208) -0.28  (0.223) -1.04  (0.193) 0.08  (0.200)
3.Secondary Outcome
Title Change From Baseline in MRSA Sputum Density.
Hide Description [Not Specified]
Time Frame Day 15 of treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT (MITT) population, which included all randomized patients who received any amount of study drug and had at least one scheduled post baseline measurement.
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description:
Vancomycin hydrochloride inhalation powder 32 mg BID
Placebo inhalation powder BID
Vancomycin hydrochloride inhalation powder 64 mg BID
Placebo inhalation powder BID
Overall Number of Participants Analyzed 19 16 19 22
Least Squares Mean (Standard Error)
Unit of Measure: Log10 CFU/mL
-0.55  (0.259) 0.09  (0.279) -1.14  (0.229) 0.26  (0.216)
4.Secondary Outcome
Title Change From Baseline in FEV1
Hide Description Absolute change from baseline in FEV1 percent predicted
Time Frame Day 29 of treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population, which included all randomized patients who received any amount of study drug and had at least one scheduled post baseline measurement.
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description:
Vancomycin hydrochloride inhalation powder 32 mg BID
Placebo inhalation powder BID
Vancomycin hydrochloride inhalation powder 64 mg BID
Placebo inhalation powder BID
Overall Number of Participants Analyzed 18 17 16 21
Least Squares Mean (Standard Error)
Unit of Measure: percentage of predicted FEV1
0.53  (1.343) 1.15  (1.356) -0.68  (1.1449) -2.61  (1.314)
5.Secondary Outcome
Title Change From Baseline in FVC
Hide Description Absolute change from baseline in FVC percent predicted
Time Frame Day 29 of treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population, which included all randomized patients who received any amount of study drug and had at least one scheduled post baseline measurement.
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description:
Vancomycin hydrochloride inhalation powder 32 mg BID
Placebo inhalation powder BID
Vancomycin hydrochloride inhalation powder 64 mg BID
Placebo inhalation powder BID
Overall Number of Participants Analyzed 18 17 16 21
Least Squares Mean (Standard Error)
Unit of Measure: percentage of predicted FVC
-0.07  (1.273) 1.67  (1.283) -0.47  (1.594) -2.48  (1.423)
6.Secondary Outcome
Title Change From Baseline in Cystic Fibrosis Respiratory Symptom Diary (CFRSD-CRISS) Scores
Hide Description Change from Baseline in Cystic Fibrosis Respiratory Symptom Diary (CFRSD) Chronic Respiratory Infection Symptom Scores (CRISS). The minimum score is 0 and the maximum is 100, where a higher score means a worse outcome.
Time Frame Day 29 of treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population, which included all randomized patients who received any amount of study drug and had at least one scheduled post baseline measurement.
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description:
Vancomycin hydrochloride inhalation powder 32 mg BID
Placebo inhalation powder BID
Vancomycin hydrochloride inhalation powder 64 mg BID
Placebo inhalation powder BID
Overall Number of Participants Analyzed 17 17 17 21
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-6.59  (2.620) -3.02  (2.614) -0.55  (2.701) -5.43  (2.552)
7.Secondary Outcome
Title Time From Start of Dosing to First Administration of Other Antimicrobial Medications (Oral, Intravenous and/or Inhaled) Due to Respiratory Symptoms.
Hide Description [Not Specified]
Time Frame Entire study: Day 1 of treatment period through 8 week post-treatment follow up visit
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population, which included all randomized patients who received any amount of study drug and had at least one scheduled post baseline measurement.
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description:
Vancomycin hydrochloride inhalation powder 32 mg BID
Placebo inhalation powder BID
Vancomycin hydrochloride inhalation powder 64 mg BID
Placebo inhalation powder BID
Overall Number of Participants Analyzed 20 20 24 23
Median (95% Confidence Interval)
Unit of Measure: days
69.5
(34.0 to 107.0)
80.0 [1] 
(23.0 to NA)
48.0
(14.0 to 66.0)
NA [2] 
(43.0 to NA)
[1]
95% CI not calculable because 50% of patients were censored at time of study completion.
[2]
Median and 95% CI not calculable because more than 50% of patients were censored at time of study completion.
8.Secondary Outcome
Title Time From Start of Dosing to Exacerbation of Signs/Symptoms (Fuchs Criteria).
Hide Description [Not Specified]
Time Frame Entire study: Day 1 of treatment period through 8 week post-treatment follow up visit
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population, which included all randomized patients who received any amount of study drug and had at least one scheduled post baseline measurement.
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description:
Vancomycin hydrochloride inhalation powder 32 mg BID
Placebo inhalation powder BID
Vancomycin hydrochloride inhalation powder 64 mg BID
Placebo inhalation powder BID
Overall Number of Participants Analyzed 20 20 24 23
Median (95% Confidence Interval)
Unit of Measure: days
107.0
(13.0 to 107.0)
NA [1] 
(13.0 to NA)
49.0
(14.0 to 84.0)
NA [1] 
(37.0 to NA)
[1]
Median and 95% CI not calculable because more than 50% of patients were censored at time of study completion.
9.Secondary Outcome
Title Change From Baseline in High Sensitivity CRP
Hide Description [Not Specified]
Time Frame Day 29 of the dosing period
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population, which included all randomized patients who received any amount of study drug and had at least one scheduled post baseline measurement.
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description:
Vancomycin hydrochloride inhalation powder 32 mg BID
Placebo inhalation powder BID
Vancomycin hydrochloride inhalation powder 64 mg BID
Placebo inhalation powder BID
Overall Number of Participants Analyzed 17 17 15 22
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-0.34  (0.132) -0.18  (0.130) 0.15  (0.223) -0.09  (0.184)
10.Secondary Outcome
Title Change From Baseline in Blood Neutrophils
Hide Description [Not Specified]
Time Frame Day 29 of the dosing period
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population, which included all randomized patients who received any amount of study drug and had at least one scheduled post baseline measurement.
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description:
Vancomycin hydrochloride inhalation powder 32 mg BID
Placebo inhalation powder BID
Vancomycin hydrochloride inhalation powder 64 mg BID
Placebo inhalation powder BID
Overall Number of Participants Analyzed 17 17 16 21
Least Squares Mean (Standard Error)
Unit of Measure: 10^9 cells/L
0.20  (0.569) 1.23  (0.561) -0.29  (0.557) 0.04  (0.487)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Hide Arm/Group Description Vancomycin hydrochloride inhalation powder 32 mg BID Placebo inhalation powder BID Vancomycin hydrochloride inhalation powder 64 mg BID Placebo inhalation powder BID
All-Cause Mortality
AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)      0/20 (0.00%)      0/24 (0.00%)      0/23 (0.00%)    
Hide Serious Adverse Events
AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/20 (20.00%)      2/20 (10.00%)      1/24 (4.17%)      4/23 (17.39%)    
General disorders         
Pain  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Infections and infestations         
Infective pulmonary exacerbation of cystic fibrosis  3/20 (15.00%)  3 2/20 (10.00%)  3 1/24 (4.17%)  1 3/23 (13.04%)  3
Pneumonia  0/20 (0.00%)  0 0/20 (0.00%)  0 0/24 (0.00%)  0 1/23 (4.35%)  1
Infective exacerbation of bronchiectasis  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Metabolism and nutrition disorders         
Hyperglycemia  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Pleural effusion  0/20 (0.00%)  0 0/20 (0.00%)  0 0/24 (0.00%)  0 1/23 (4.35%)  1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AeroVanc 32 mg Placebo to 32 mg AeroVanc 64 mg Placebo to 64 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/20 (90.00%)      18/20 (90.00%)      20/24 (83.33%)      19/23 (82.61%)    
Gastrointestinal disorders         
Diarrhoea  0/20 (0.00%)  0 0/20 (0.00%)  0 3/24 (12.50%)  3 0/23 (0.00%)  0
Abdominal pain upper  0/20 (0.00%)  0 1/20 (5.00%)  1 0/24 (0.00%)  0 0/23 (0.00%)  0
Constipation  0/20 (0.00%)  0 1/20 (5.00%)  1 0/24 (0.00%)  0 0/23 (0.00%)  0
General disorders         
Fatigue  5/20 (25.00%)  6 4/20 (20.00%)  6 8/24 (33.33%)  8 3/23 (13.04%)  3
Exercise tolerance decreased  5/20 (25.00%)  5 1/20 (5.00%)  1 2/24 (8.33%)  2 2/23 (8.70%)  2
Chest discomfort  2/20 (10.00%)  2 0/20 (0.00%)  0 4/24 (16.67%)  4 0/23 (0.00%)  0
Malaise  0/20 (0.00%)  0 1/20 (5.00%)  1 0/24 (0.00%)  0 0/23 (0.00%)  0
Pain  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Product taste abnormal  0/20 (0.00%)  0 1/20 (5.00%)  1 0/24 (0.00%)  0 0/23 (0.00%)  0
Infections and infestations         
Infective pulmonary exacerbation of cystic fibrosis  3/20 (15.00%)  3 5/20 (25.00%)  5 5/24 (20.83%)  5 2/23 (8.70%)  2
Nasopharyngitis  0/20 (0.00%)  0 1/20 (5.00%)  1 0/24 (0.00%)  0 1/23 (4.35%)  1
Upper respiratory tract infection  0/20 (0.00%)  0 1/20 (5.00%)  1 0/24 (0.00%)  0 0/23 (0.00%)  0
Vulvovaginal mycotic infection  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Injury, poisoning and procedural complications         
Muscle strain  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Investigations         
Forced expiratory volume decreased  4/20 (20.00%)  4 2/20 (10.00%)  2 3/24 (12.50%)  3 1/23 (4.35%)  1
Weight decreased  4/20 (20.00%)  6 1/20 (5.00%)  1 2/24 (8.33%)  2 1/23 (4.35%)  1
Blood potassium increased  0/20 (0.00%)  0 1/20 (5.00%)  1 0/24 (0.00%)  0 0/23 (0.00%)  0
Peak expiratory flow rate decreased  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Pulmonary function test decreased  0/20 (0.00%)  0 1/20 (5.00%)  1 0/24 (0.00%)  0 0/23 (0.00%)  0
Metabolism and nutrition disorders         
Decreased appetite  0/20 (0.00%)  0 2/20 (10.00%)  2 3/24 (12.50%)  3 4/23 (17.39%)  4
Musculoskeletal and connective tissue disorders         
Jaw cyst  0/20 (0.00%)  0 1/20 (5.00%)  1 0/24 (0.00%)  0 0/23 (0.00%)  0
Nervous system disorders         
Sinus headache  4/20 (20.00%)  4 1/20 (5.00%)  1 2/24 (8.33%)  3 3/23 (13.04%)  3
Dysgeusia  2/20 (10.00%)  2 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Headache  1/20 (5.00%)  1 1/20 (5.00%)  1 0/24 (0.00%)  0 0/23 (0.00%)  0
Lethargy  0/20 (0.00%)  0 1/20 (5.00%)  1 0/24 (0.00%)  0 0/23 (0.00%)  0
Renal and urinary disorders         
Dysuria  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Hematuria  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Cough  9/20 (45.00%)  14 7/20 (35.00%)  12 9/24 (37.50%)  11 10/23 (43.48%)  11
Respiratory tract congestion  8/20 (40.00%)  10 4/20 (20.00%)  5 7/24 (29.17%)  7 7/23 (30.43%)  8
Sputum increased  6/20 (30.00%)  6 7/20 (35.00%)  7 6/24 (25.00%)  6 5/23 (21.74%)  6
Dyspnoea exertional  4/20 (20.00%)  4 2/20 (10.00%)  2 5/24 (20.83%)  6 3/23 (13.04%)  3
Paranasal sinus hypersecretion  6/20 (30.00%)  7 3/20 (15.00%)  3 4/24 (16.67%)  4 1/23 (4.35%)  2
Increased viscosity of bronchial secretion  1/20 (5.00%)  1 3/20 (15.00%)  3 3/24 (12.50%)  4 2/23 (8.70%)  2
Dyspnoea  3/20 (15.00%)  3 1/20 (5.00%)  1 2/24 (8.33%)  2 0/23 (0.00%)  0
Haemoptysis  1/20 (5.00%)  1 0/20 (0.00%)  0 1/24 (4.17%)  1 4/23 (17.39%)  4
Sputum discoloured  0/20 (0.00%)  0 1/20 (5.00%)  1 2/24 (8.33%)  2 1/23 (4.35%)  1
Wheezing  1/20 (5.00%)  1 2/20 (10.00%)  2 1/24 (4.17%)  1 0/23 (0.00%)  0
Bronchospasm  0/20 (0.00%)  0 0/20 (0.00%)  0 2/24 (8.33%)  2 0/23 (0.00%)  0
Oropharyngeal pain  2/20 (10.00%)  2 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Rales  1/20 (5.00%)  1 1/20 (5.00%)  1 0/24 (0.00%)  0 0/23 (0.00%)  0
Rhinorrhoea  0/20 (0.00%)  0 1/20 (5.00%)  1 0/24 (0.00%)  0 1/23 (4.35%)  1
Rhinitis allergic  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Throat tightness  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Skin and subcutaneous tissue disorders         
Pruritus  1/20 (5.00%)  1 0/20 (0.00%)  0 0/24 (0.00%)  0 0/23 (0.00%)  0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Head of Clinical Development
Organization: Savara Inc.
Phone: +45 7930 1414
EMail: info@savarapharma.com
Layout table for additonal information
Responsible Party: Savara Inc.
ClinicalTrials.gov Identifier: NCT01746095    
Other Study ID Numbers: SAV005-02
First Submitted: December 6, 2012
First Posted: December 10, 2012
Results First Submitted: June 1, 2019
Results First Posted: January 13, 2020
Last Update Posted: January 13, 2020