Adjunctive Therapy to Antibiotics in the Treatment of S. Aureus Ventilator-Associated Pneumonia With AR-301 (AR-301-002)
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|ClinicalTrials.gov Identifier: NCT03816956|
Recruitment Status : Recruiting
First Posted : January 25, 2019
Last Update Posted : January 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Lung Infection Pneumonia, Ventilator-Associated Infection, Bacterial Staphylococcus Aureus||Drug: AR-301 Other: Placebo||Phase 3|
This study is an international, multicenter, prospective, randomized, double blind, placebo controlled, parallel design protocol in patients with Ventilator-Associated Pneumonia (VAP) caused by S. aureus.
Patients with a documented diagnosis of pneumonia due to S. aureus, and require ICU care, who have been intubated (or have a tracheostomy tube in place) and mechanically ventilated for at least 48 hours are eligible for screening.
In total, approximately 240 subjects will be randomized 1-1 to be treated with placebo plus standard of care (SOC) or AR-301 (20 mg/kg) plus SOC in this Phase 3 study.
Study subjects will receive a single treatment dose at Day 0 in addition to SOC antibiotic treatment, and then enter a safety, efficacy and PK study period for a total study duration of 28 days. The selection of SOC antibiotics is made in accordance with local best practices at the discretion of the investigator.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||240 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||A Randomized Double-blind Placebo-controlled Multicenter Phase 3 Study of Efficacy and Safety of AR-301 as Adjunct Therapy to Antibiotics in the Treatment of Ventilator-Associated Pneumonia (VAP) Caused by S. Aureus|
|Actual Study Start Date :||May 3, 2019|
|Estimated Primary Completion Date :||August 2020|
|Estimated Study Completion Date :||August 2020|
Experimental: Study treatment
Investigational/ Interventional Product group: AR-301 (tosatoxumab) 20 mg/kg administered once intravenously the day of enrolment.
AR-301 (tosatoxumab) 20 mg/kg administered once intravenously the day of enrolment.
Other Name: Salvecin
Placebo Comparator: Placebo treatment
Control group: Placebo administered intravenously the day of enrolment.
- A comparison of Clinical Cure Rates of standard of care (SOC) alone and SOC with AR-301 [ Time Frame: 21 days ]Clinical cure rates of standard of care (SOC) alone and (SOC) with AR-301 at Day 21 as measured by all-cause mortality, need for mechanical ventilation and signs and symptoms of pneumonia.
- Safety of AR-301 by treatment-emergent adverse events assessed by changes between treatment and placebo as assessed by the Principal Investigator [ Time Frame: 21 Days ]Safety of AR-301 of treatment-emergent adverse events as assessed by changes assessed by the PI between treatment and placebo
- Tolerability of AR-301 measured by the number of participants with treatment-emergent adverse events classified using CTCAE v 5.0 [ Time Frame: 21 Days ]Tolerability of AR-301 will be measured and evaluated by the severity of treatment-emergent adverse events using the CTCAE v 5.0.
- The difference in clinical cure rates between Standard of Care alone or with AR301 as time to clinical cure at Day 7, 14 and 28 [ Time Frame: Day 7, 14, and 28 ]Difference in Clinical Cure rates between SOC alone or with AR-301 defined by time to clinical cure (number of days) using the same criteria as for the primary efficacy objective at Day 21.
- The difference in mortality between Standard of Care alone or with AR-301 at Days 7,14,28 [ Time Frame: Day 7, 14, and 28 ]Difference in mortality defined as cause of death (all-cause mortality and pneumonia-related mortality)between SOC alone or with AR-301 at Days 7,14, and 28
- The difference in PaO2/FiO2 between Standard of Care alone or with AR-301 at Days 7,14,28 [ Time Frame: Day 7, 14, and 28 ]Difference in respiratory function between SOC alone or with AR-301 at Days 7,14, and 28 as changes in PaO2/FiO2 ratio (e.g. by arterial blood gases), if available and whenever possible OR changes in non-invasive measures of oxygenation (e.g. by pulse oximetry)
- The difference in time on supplemental oxygen assessment between Standard of Care alone or with AR-301 at Days 7,14,28 [ Time Frame: Day 7, 14, and 28 ]Difference in respiratory function between SOC alone or with AR-301 at Days 7,14, and 28 as time on supplemental oxygen
- Changes in baseline in SOFA score between Standard of Care alone or with AR301 at Days 7,14,28 [ Time Frame: Day 7, 14, and 28 ]
Difference in Clinical Cure rates between SOC alone or with AR-301 at Days 7,14, and 28 in the following clinical outcomes:
Changes from Baseline in sequential organ failure assessment (SOFA) score using the following scale: Maximum SOFA score 0-6, <10% Mortality, 7-9 15-20% mortality, 10-12 40-50% mortality, 13-14 50-60% mortality, 15 >80% mortality, 15-24 >90% mortality. Lower numbers are considered to be better outcome of mortality and higher scores worse outcome of mortality.
- Duration of intubation with ventilation [ Time Frame: 28 days ]Number of days with intubation with ventilation
- Duration mechanical ventilation if tracheostomy in place [ Time Frame: 28 days ]Number of days of intubation with mechanical ventilation if tracheostomy in place
- Duration of stay in ICU [ Time Frame: 28 days ]Number of days of stay in ICU
- Duration hospitalization [ Time Frame: 28 days ]Number of days of hospitalization
- Duration antibiotic use. [ Time Frame: 28 days ]Number of days on antibiotics
- Pharmacokinetic Analysis - (Cmax) [ Time Frame: 28 days ]Pharmacokinetic analysis measuring Maximum Serum Concentration (Cmax)
- Pharmacokinetic Analysis - (AUC) [ Time Frame: 28 Days ]Pharmacokinetic analysis measuring Area Under the Curve (AUC)
- Pharmacokinetic Analysis - (T1/2) [ Time Frame: 28 Days ]Pharmacokinetic analysis measuring time for half of the initial dose of study drug to be eliminated from the body (T1/2)
- Pharmacokinetic Analysis - (Tmax) [ Time Frame: 28 Days ]Pharmacokinetic analysis measuring time at which Cmax is obtained (Tmax)
- Pharmacokinetic Analysis (Blood levels of AR-301) [ Time Frame: 28 Days ]Blood levels of AR-301 in the patient over time during the study period.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03816956
|Contact: Lynne M Deans, MT||925-200-3089 ext email@example.com|
|Contact: Ouadah M Hadjebi||+33 777 86 06 99 ext firstname.lastname@example.org|
|Study Director:||Lynne M Deans, MT||Aridis Pharmaceuticals|