A Study of the Combination of Experimental AR-301 and Antibiotics for Staphylococcus Aureus Ventilator-Associated Pneumonia

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"Volunteer for research at UC Davis and contribute to discoveries that may improve health care for you, your family, and your community!"
Age: 18 years or older
Gender:
Any
Healthy Volunteers: No
Keywords: S. aureus, bacteria, staph, staphylococcus aureus, pneumonia
Type: Drug study, Phase 3
Target:
10 Participants
Investigator:
Description
We invite you to take part in a research study because because you may have pneumonia, possibly caused by the bacteria Staphylococcus aureus (S. aureus). Pneumonia is a severe infection of the lungs. Because of this infection, you have been admitted to the intensive care unit (ICU) and have undergone mechanical intubation (a medical procedure in which a tube is placed into the windpipe and a machine is helping you breathe).

The purpose of this study is to test an experimental drug called AR-301 in people diagnosed with pneumonia. AR-301 is an antibody created in a lab to act as an immunoglobulin (a protein the body naturally produces to combact infections). It is designed to target toxins created by a specific bacteria called Staphylocccocus aureus (S. aureus).

AR-301 is an experimental drug. This means that AR-301 is still being studied. The efficacy and safety of the product have not been fully established. It also means it is not approved for use by the FDA.

This is a placebo-controlled study. A placebo is an inactive substance, designed to look like the experimental study drug. Researchers will compare the effects of taking AR-301 to the effects of taking a placebo.

The purpose of this study is to test the safety, tolerability, and effectiveness of a single dose of AR-301. It will be given in combination with standard-of-care antibiotic therapy. The effects will be compared to placebo given in combination with standard-of-care antibiotic therapy. These effects will be tested in patients with S. aureus pneumonia.

If you take part in this study, you will have a 50% chance to receive AR-301 as opposed to placebo. Each treatment group (AR-301 or placebo) will receive the best possible antibiotic chosen by your physician. In this study, the placebo is made up of normal saline and the inactive ingredients of the study drug. Treatment is delivered into your vein in the same way as the study drug.

Whether you receive the placebo or the study drug is determined randomly, like the flipping of a coin. Your chances of receiving study drug are one in two, or 50%. The placebo looks very similar to the study drug, but contains no active ingredients. Neither you nor your study doctor will know whether you are receiving the active study drug or the placebo.
This study requires

The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.

Who can participate

Inclusion Criteria

  1. Written Informed Consent given by the patient or, if not possible, by a legally acceptable representative and/or an independent physician 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. South Korea only: To be at least 19 years of age.

  3. Treated in an ICU at the time of enrollment.

  4. Endotracheal tube in place (tracheostomy is allowed).

  5. The patient is mechanically ventilated for at least 48 hours.

  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. 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. 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.

  1. Documented pulmonary infection with S. aureus obtained by bronchoalveolar lavage (BAL), mini-BAL, endotracheal aspiration/aspirate (ETA) (collectively ‘airway specimen’). For the study randomization, S. aureus must be identified by one of the two methods below (more than one pathogen allowed, if S. aureus is regarded as a pneumonia causing pathogen requiring S. aureus targeting antibiotic therapy):

a. An airway specimen, culture positive by any method for S. aureus obtained less than 72 hours prior to randomization. This sample will be used for baseline standard microbial culture by the local laboratory (including organism identification, quantitative or semi-quantitative culture and susceptibility testing). OR b. A rapid diagnostic test. In such case, the same sample must ALSO be used for standard microbial culture by the local laboratory (including organism identification, quantitative or semi-quantitative culture and susceptibility testing). The corresponding culture results are NOT required prior to randomization.

Exclusion Criteria

  1. The subject is unlikely to survive for the study duration despite delivery of adequate antibiotics and supportive care for treatment of S. aureus pneumonia.

  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 < 200. b. Expected neutropenia due to chemotherapy. c. Absolute neutrophil count less than 500/µL (mm3 ). d. Organ transplant requiring systemic immunosuppressive therapy within the past 6 months. e. Chronic administration of systemic corticosteroids, defined as > 40 mg of prednisone or equivalent per day administered within 14 days prior to the first dose of study drug.

  1. Known hereditary complement deficiency.

  2. 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]).

  3. 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.

  4. Patient has received IV immunoglobulin therapy within 3 months prior to the Screening Visit.

  5. 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. Non-pregnant 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.

  6. Any sexually active subject 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.

  7. Known lack of treatment compliance from prior studies or ongoing medical care based on medical records and PI’s judgment and/or the capacity of the patient to comply with all study requirements.

  8. Any medical, psychological, cognitive, social or legal conditions that would interfere in the ability to give an Informed Consent OR the absence of a legally acceptable representative of the patient or independent physician allowed and able to give consent on his/her behalf.

  9. Participation as a subject in another interventional study within 30 days prior to the first dose of study treatment, or planned participation in such a study during the study or within 30 days of its completion by the patient. Patients who are not receiving/have not received interventional active study drug (e.g. placebo) or medications/procedures except for SOC within the timeframe described above are eligible for this protocol. Patients who participate in observational or epidemiological studies are also eligible provided this does not interfere with their capacity or the capacity of the study staff to comply with all study requirements.

Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study team will discuss the risks associated with taking part in this research study.
Compensation
You will be compensated for taking part in this study. You will be paid $50 for any visit that requires you return to the hospital. The maximum compensation you can receive for participating in this study is $250. You will not receive any reimbursement for visits that you do not complete. You will receive your payment by check after the end of your participation in the study.
Resources
Schedule
Study duration and period
We expect that you will be in this research study for approximately 1 month.
Recruitment period
From Aug. 26, 2019
Location
UC Davis Medical Center
2315 Stockton Boulevard
Sacramento, CA 95817
Research Topic
Conditions:
  • Lung Infection
  • Pneumonia
  • Ventilator-Associated
  • Infection
  • Bacterial
  • Staphylococcus Aureus

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