Adjunctive Therapy to Antibiotics in the Treatment of S. Aureus Ventilator-Associated Pneumonia With AR-301

NCT03816956 | Completed Phase 3 FDA Drug

• 1 other identifier: AR-301-002
• Study Type: interventional
• Target: 174
• Locations: 13 countries
• Sites: 41

Brief Summary

AR-301 is being evaluated as an adjunctive treatment of ventilator-associated pneumonia (VAP) due to Staphylococcus aureus (S. aureus) in combination with standard of care (SOC) antibiotic therapy in patients with confirmed S. aureus infection.

Conditions

Lung Infection; Pneumonia, Ventilator-Associated; Infection, Bacterial; Staphylococcus Aureus

Keywords

Staphylococcus aureus; S. aureus; monoclonal antibody; Aridis; VAP; ventilator acquired pneumonia; infection; pneumonia; AR301

Outcome Measures

Primary Outcomes (3)

• A comparison of Clinical Cure Rates of standard of care (SOC) alone and SOC with AR-301

  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.

  21 days

• Safety of AR-301 by treatment-emergent adverse events assessed by changes between treatment and placebo as assessed by the Principal Investigator

  Safety of AR-301 of treatment-emergent adverse events as assessed by changes assessed by the PI between treatment and placebo

  21 Days

• Tolerability of AR-301 measured by the number of participants with treatment-emergent adverse events classified using CTCAE v 5.0

  Tolerability of AR-301 will be measured and evaluated by the severity of treatment-emergent adverse events using the CTCAE v 5.0.

  21 Days

Secondary Outcomes (15)

• 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

  Day 7, 14, and 28

• The difference in mortality between Standard of Care alone or with AR-301 at Days 7,14,28

  Day 7, 14, and 28

• The difference in PaO2/FiO2 between Standard of Care alone or with AR-301 at Days 7,14,28

  Day 7, 14, and 28

• The difference in time on supplemental oxygen assessment between Standard of Care alone or with AR-301 at Days 7,14,28

  Day 7, 14, and 28

• Changes in baseline in SOFA score between Standard of Care alone or with AR301 at Days 7,14,28

  Day 7, 14, and 28

Study Arms (2)

Study treatment

EXPERIMENTAL

Investigational/ Interventional Product group: AR-301 (tosatoxumab) 20 mg/kg administered once intravenously on the day of randomization.

Drug: AR-301

Placebo treatment

PLACEBO COMPARATOR

Control group: Placebo administered intravenously on the day of randomization.

Other: Placebo

Interventions

AR-301 DRUG

AR-301 (tosatoxumab) 20 mg/kg administered once intravenously the day of enrolment.

Also known as: AR-301 (tosatoxumab)

Study treatment

Placebo OTHER

Placebo comparator

Placebo treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Treated in an ICU at the time of enrollment.
• Endotracheal tube in place (tracheostomy is allowed).
• The patient is mechanically ventilated for at least 48 hours.
• Diagnosis of pneumonia based on the following criteria (a, b, and c, all must be met):
• One definitive chest X-ray diagnostic of pneumonia within 48 hours,
• Hypoxemia based on PaO2/FiO2.
• 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.
• Documented pulmonary infection with Staphylococcus aureus obtained by bronchoalveolar lavage (BAL), mini-BAL, protected endotracheal aspiration/aspirate (ETA) (collectively 'airway specimen').

You may not qualify if:

• The subject is unlikely to survive for the study duration despite delivery of adequate antibiotics and supportive care for treatment of S. aureus pneumonia.
• Effective antibacterial drug therapy for the index pneumonia administered continuously for 48 hours or more prior to initiation of study treatment. Effective antibiotics would include those typically used to treat S. aureus.
• Plasmapheresis (ongoing or planned), extracorporeal membrane oxygenation (ECMO) or any procedure that would remove/filter out the monoclonal antibody/study drug.
• Immunocompromised patients.
• Known hereditary complement deficiency.
• Liver dysfunction with a Child Pugh C score \> 9 (Child Pugh score of A or B are acceptable at discretion of the Principal Investigator \[PI\]).
• 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).
• Patient has received intravenous (IV) immunoglobulin therapy within 3 months prior to the Screening Visit.
• 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.
• Any sexually active subject who is unwilling to use acceptable methods of contraception for 120 days after dosing.
• 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.
• 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 valid representative of the patient or independent physician allowed and able to give consent on his/her behalf.
• 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.

Sponsors & Collaborators

• Aridis Pharmaceuticals, Inc.: lead

Study Sites (45)

BLR-06

Grodno, 230017, Belarus

Location

BLR-04

Homyel, 246029, Belarus

Location

BLR-01

Minsk, 223041, Belarus

Location

BEL-01

Lodelinsart, 6042, Belgium

Location

BEL-05

Ottignies, 1340, Belgium

Location

BRA-08

Curitiba, 80810-050, Brazil

Location

BRA-04

Curitiba, 82050-350, Brazil

Location

CHN-09

Guangzhou, Guangdong, 510180, China

Location

EST-01

Tallinn, 13419, Estonia

Location

FRA-02

Strasbourg, Cedex, 67091, France

Location

FRA-18

Brive-la-Gaillarde, 19312, France

Location

FRA-10

Bron, 69677, France

Location

FRA-05

La Roche-sur-Yon, 85925, France

Location

FRA-04

Limoges, 87042, France

Location

FRA-01

Nantes, 44093, France

Location

FRA-16

Orléans, 45067, France

Location

FRA-11

Rennes, 35033, France

Location

FRA-13

Trévenans, 90400, France

Location

GEO-06

Gori, 1400, Georgia

Location

GEO-01

Kutaisi, 4600, Georgia

Location

GEO-03

Kutaisi, 4600, Georgia

Location

GEO-04

Kutaisi, 4600, Georgia

Location

GEO-10

Kutaisi, 4600, Georgia

Location

GEO-02

Tbilisi, 0141, Georgia

Location

GEO-09

Tbilisi, 0159, Georgia

Location

GEO-07

Tbilisi, 0160, Georgia

Location

ISR-04

Haifa, 31096, Israel

Location

ISR-01

Ramat Gan, 5262100, Israel

Location

LVA-02

Riga, LV-1006, Latvia

Location

MEX-07

Guadalajara, Jalisco, 44280, Mexico

Location

RUS-18

Arkhangelsk, 163002, Russia

Location

RUS-11

Chelyabinsk, 454000, Russia

Location

RUS-01

Krasnoyarsk, 660022, Russia

Location

RUS-04

Novosibirsk, 630051, Russia

Location

RUS-02

Saint Petersburg, 192242, Russia

Location

RUS-10

Smolensk, 214018, Russia

Location

RUS-16

Zhukovskiy, 140180, Russia

Location

ZAF-09

Johannesburg, 2193, South Africa

Location

ESP-01

Madrid, 28040, Spain

Location

TUR-06

Istanbul, 34214, Turkey (Türkiye)

Location

TUR-01

Trabzon, 61080, Turkey (Türkiye)

Location

UKR-05

Chernivtsi, 58000, Ukraine

Location

UKR-03

Ivano-Frankivsk, 76008, Ukraine

Location

UKR-02

Kharkiv, 61103, Ukraine

Location

UKR-09

Kharkiv, 61103, Ukraine

Location

Related Links

• Website of the Sponsor

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Bacterial Infections; Staphylococcal Infections; Infections; Pneumonia

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections

Study Officials

• Hasan S Jafri, MD, FAAP

  Aridis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2018
• First Posted: January 25, 2019
• Study Start: May 3, 2019
• Primary Completion: October 28, 2022
• Study Completion: October 28, 2022
• Last Updated: July 6, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

LA (1); IL (2); ZA (1); ES (1); ME (1); GE (8); BR (2); TU (2); RU (7); UA (4); FR (9); CN (1); BE (2)