Staphylococcus aureus pneumonia MedDRA version: 20.0 Level: PT Classification code 10035734 Term: Pneumonia staphylococcal System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: tosatoxumab
Product Code: AR-301, KBSA301
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: tosatoxumab
Current Sponsor code: AR-301
Other descriptive name: KBSA301
Concent
Sponsors
Aridis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written Informed Consent given by the study patient or, if not possible, by a legally acceptable representative of the study patient and/or an independent physician/council of independent physicians (CIP), as authorized by the competent ethics committee (EC) or independent review board (IRB) and local regulations. 2. To be at least 18 years of age. Taiwan only: To be at least 20 years of age. 3. Treated in an ICU at the time of enrollment. 4. Endotracheal tube in place (tracheostomy is allowed), 5. The study patient is mechanically ventilated for at least 48 hours prior to the diagnosis of pneumonia. 6. Diagnosis of pneumonia based on the following criteria (a, b, and c, all must be met): a. One definitive chest X-ray diagnostic of pneumonia within 48 hours. b. Hypoxemia based on at least one of the following measurements criteria: i. Worsening in PaO2/FiO2 < 250 mmHg (at sea level or equivalent for significant elevations above sea level) while intubated and mechanically ventilated, as one or more measures within = 48 hours prior to randomization, or ii. Worsening in PaO2 < 60 mmHg (at sea level or equivalent for significant elevations above sea level) while intubated and mechanically ventilated, as one or more measures within = 48 hours prior to randomization. c. At least one of the following signs: i. Documented fever (e.g., body temperature greater than or equal to 38º Celsius). ii. Hypothermia (e.g., core body temperature less than or equal to 35º Celsius). iii. Total peripheral white blood cell (WBC) count greater than or equal to 10,000 cells/µL (or mm3). iv. Leukopenia with total WBC less than or equal to 4,500 cells/µL (mm3). v. Greater than 15 percent immature neutrophils (bands) noted on peripheral blood smear. 7. Documented pulmonary infection with S. aureus obtained by BAL, mini-BAL or ETA (collectively ‘airway specimen’). For the study randomization, S. aureus must be identified as the primary pneumonia causing pathogen requiring S. aureus targeted antibiotic therapy using a or b below. More than one pathogen is allowed, if S. aureus is regarded as the primary pneumonia causing pathogen. A rapid diagnostic test such as BioFire’s FilmArray (FA), Cepheid’s GeneXpert (GX), mass spectrometry, PCR, and/or a semi quantitative Gram stain may be used for confirmation of S. aureus prior to randomization. a. In such case, the same sample must ALSO be used for standard microbiological culture test by the local laboratory (including organism identification, quantitative or semi-quantitative culture and susceptibility testing). In addition, the airway specimen will be sent to central laboratory for bioavailability testing. The corresponding culture results are NOT required prior to randomization, however, a positive microbiological culture for S. aureus is required to be part of micro-ITT population. b. A standard microbiological culture test for S. aureus that is obtained less than 72 hours prior to randomization. This sample will be used for baseline standard microbiological culture by the local laboratory (including organism identification, quantitative or semi quantitative culture and susceptibility testing). In addition, the airway specimen will be sent to central laboratory for bioavailability testing. 8.Approval by a Clinical Coordinating Committee (CCC) member must be obtained prior to randomization. Are the trial subjects under 18? no Number of subjects for this age range: F.1
Exclusion criteria
Exclusion criteria: 1. The study patient is unlikely to survive for the study duration(i.e., for at least 28 days) despite delivery of adequate antibiotics and supportive care for treatment of S. aureus VAP. 2. Effective antibacterial drug therapy for the index pneumonia administered continuously for more than 72 hours prior to initiation of study treatment. Effective antibiotics include intravenous (IV) and/or oral medications typically used to treat S. aureus. 3. Plasmapheresis (ongoing or planned), extracorporeal membrane oxygenation (ECMO) or any procedure that would remove/filter out the monoclonal antibody (mAb)/study drug. 4. Immunocompromised patients due to, but not limited to the following: a. HIV / AIDS who are not stable under medication and/or most recent CD4 40 mg of prednisone or equivalent per day administered within 14 days prior to the first dose of study drug. 5. Known hereditary complement deficiency. 6. Liver dysfunction with a Child Pugh C score > 9 (Child Pugh score of A or B are acceptable at discretion of the Principal Investigator [PI]). 7. Pulmonary disease that precludes evaluation of a therapeutic response (such as lung cancer resulting in bronchial obstruction or on the same side as the pneumonia, active tuberculosis, cystic fibrosis, granulomatous disease, fungal pulmonary infection, lung abscess, pleural empyema or post obstructive pneumonia). Chronic obstructive pulmonary disease (COPD) is not an exclusion criterion. 8. Study patient has received IV immunoglobulin therapy within 3 months prior to the Screening Visit. 9. Any woman of child-bearing potential (WOCBP) who does not have a negative pregnancy test result at Screening using SERUM or URINE testing based on Beta-subunit human chorionic gonadotropin (HCG) standard tests and methods from the local laboratory. Serum pregnancy screening for WOCBP would be preferable, where possible. Nonpregnant with confirmation via local laboratory testing is required. Lactating women are also excluded. Women who are post-menopausal as evidenced by the absence of menstruation for at least 1 year are eligible; the date of last menstruation is to be recorded in the study files unless post-menopausal status is obvious due to age. 10. Any sexually active study patient who is unwilling to use acceptable methods of contraception for 120 days after dosing. WOCBP must agree to use an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, barrier methods, abstinence) or male partner sterilization alone for the duration of the study and for at least 120 days after dosing. Males with female partners of reproductive potential must agree to practice abstinence or to use a condom (male) plus an additional barrier method (female partner) of contraception for the duration of the study and for at least 120 days after dosing. 11. Known lack of treatment compliance from prior studies or ongoing medical care based on medical records and Principal Investigator’s judgment and/or the capacity of the study patient to comply with all study requirements. 12. Any medical, psychological, cognitive, social or legal conditions that would interfere
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy: To assess the difference in Clinical Cure rates between SOC alone and SOC with AR-301 at Day 21. Stringent Clinical Cure criteria have been defined in collaboration with clinical experts in the field. Safety: To assess the clinical safety and tolerability of AR-301 in the study population.;Secondary Objective: Efficacy: To assess the difference the following clinical outcomes between SOC alone and SOC with AR-301: -Clinical Cure rates at Day 7, 14 and 28, using the same criteria as for the primary efficacy objective at Day 21 _Time to Clinical Cure _All-cause mortality, Pneumonia-related mortality _Respiratory functional assessment _Overall clinical status _Health economics Outcomes: 1. Duration of intubation with ventilation or duration of mechanical ventilation if tracheostomy is in place. 2.Duration of stay in the ICU. 3.Duration of hospitalization. 4.Duration of antibiotic utilization. _Pharmacokinetics Safety: To assess the immunogenicity of AR-301. Microbiological Efficacy: To assess the difference in eradication of index S. aureus at Day 21 and Day 28.;Primary end point(s): Primary Clinical Efficacy endpoints: The proportion of study patients with Clinical Cure at Day 21. Microbiological Endpoints: 1. Microbiological outcome of the index S. aureus pneumonia based on the data provided by the local microbiology laboratory. 2. Eradication of S. aureus at Day 21 and Day 28. Safety Endpoints: 1. Assessment of clinical adverse events, 2. Assessment of clinical laboratory safety tests, 3. Assessment of immunogenicity to AR-301.;Timepoint(s) of evaluation of this end point: Clinical Cure of pneumonia will be assessed daily by the investigator. “Clinical Cure” rates will be analyzed on Day 7, 14, 21 (primary efficacy endpoint) and 28. Clinical safety assessments will be performed on an ongoing basis while predefined laboratory assessments will be performed at baseline, and thereafter at Day 4, 7, 14, 21, and 28. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Clinical Efficacy Endpoints: 1. Proportion of study patients with Clinical Cure at Day 14 2. Proportion of study patients with Clinical Cure at Day 28 3. All-cause mortality 4. Pneumonia-related mortality 5. Proportion of study patients with Clinical Cure at Day 7 6. Change from baseline in respiratory functional assessment. 7. Mean change from baseline in overall clinical status measured by SOFA scores 8. Health economics Outcomes;Timepoint(s) of evaluation of this end point: Secondary efficacy and health economics endpoints will be assessed in a similar manner during the 28-day period, daily when possible (e.g., time on mechanical ventilation, including if tracheostomy is in place; time on supplemental oxygenation; measures of respiratory health such as changes in PaO2/FiO2, using arterial blood gases (ABG) and/or pulse oximetry measurements), or upon occurrence (e.g., duration of intubation with ventilation, or duration of mechanical ventilation if tracheostomy is in place, duration of stay in the ICU, duration of hospitalization, antibiotic utilization). | — |
Countries
Belarus, Belgium, Brazil, China, Estonia, France, Georgia, India, Israel, Latvia, Mexico, Russian Federation, Serbia, South Africa, Spain, Turkey, Ukraine, United States
Contacts
Public ContactMendelman Paul
Aridis Pharmaceuticals, Inc.
Outcome results
None listed