Lung InfectionPhase 3AR-301-002NCT03816956
Adjunctive Therapy to Antibiotics in the Treatment of S. Aureus Ventilator-Associated Pneumonia With AR-301
A Phase 3 study testing AR-301 in people with Lung Infection and Pneumonia, Ventilator-Associated, run by Aridis Pharmaceuticals, Inc. at 45 sites in 15 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Infection, Pneumonia, Ventilator-Associated, Infection, Bacterial
- What is being tested?
- AR-301
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 174 participants
- Where
- 45 sitesin 15 countries
- Study dates
- 3 May 2019to 28 Oct 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
Show all 14Show fewer
- One definitive chest X-ray diagnostic of pneumonia within 48 hours,
- Hypoxemia based on PaO2/FiO2.
- At least one of the following signs:
- Documented fever (e.g., body temperature greater than or equal to 38º Celsius).
- Hypothermia (e.g., core body temperature less than or equal to 35º Celsius).
- Total peripheral white blood cell (WBC) count greater than or equal to 10,000 cells/µL (or mm3).
- 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').
Who cannot join
- 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]).
Show all 13Show fewer
- 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.
Trial locations and contacts
45 sites in 15 countries.
45 sites in 15 countries
France9 sites
FRA-18
Brive-la-Gaillarde, 19312
FRA-10
Bron, 69677
FRA-05
La Roche-sur-Yon, 85925
FRA-04
Limoges, 87042
FRA-01
Nantes, 44093
FRA-16
Orléans, 45067
FRA-11
Rennes, 35033
FRA-02
Strasbourg, Cedex, 67091
FRA-13
Trévenans, 90400
Georgia8 sites
GEO-06
Gori, 1400
GEO-01
Kutaisi, 4600
GEO-03
Kutaisi, 4600
GEO-04
Kutaisi, 4600
GEO-10
Kutaisi, 4600
GEO-02
Tbilisi, 0141
GEO-09
Tbilisi, 0159
GEO-07
Tbilisi, 0160
Russia7 sites
RUS-18
Arkhangelsk, 163002
RUS-11
Chelyabinsk, 454000
RUS-01
Krasnoyarsk, 660022
RUS-04
Novosibirsk, 630051
RUS-02
Saint Petersburg, 192242
RUS-10
Smolensk, 214018
RUS-16
Zhukovskiy, 140180
Ukraine4 sites
UKR-05
Chernivtsi, 58000
UKR-03
Ivano-Frankivsk, 76008
UKR-02
Kharkiv, 61103
UKR-09
Kharkiv, 61103
About this study
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
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.
Read the detailed description
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 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.
- Conditions
- Lung Infection, Pneumonia, Ventilator-Associated, Infection, Bacterial, Staphylococcus Aureus
- Being tested
- AR-301, Placebo
- Keywords
- Staphylococcus aureus, S. aureus, monoclonal antibody, Aridis, VAP, ventilator acquired pneumonia, infection, pneumonia, AR301
- Medical subject headings
- Pneumonia, Ventilator-Associated, Bacterial Infections, Staphylococcal Infections, Infections, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AR-301Drug
Also called AR-301 (tosatoxumab)
AR-301 (tosatoxumab) 20 mg/kg administered once intravenously the day of enrolment.
PlaceboOther
Placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| Study treatment | Experimental | Investigational/ Interventional Product group: AR-301 (tosatoxumab) 20 mg/kg administered once intravenously on the day of randomization. Receives: Drug: AR-301 |
| Placebo treatment | Placebo comparator | Control group: Placebo administered intravenously on the day of randomization. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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.
Measured: 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
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.
Measured: Day 7, 14, and 28
The difference in mortality between Standard of Care alone or with AR-301 at Days 7,14,28
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
Measured: Day 7, 14, and 28
The difference in PaO2/FiO2 between Standard of Care alone or with AR-301 at Days 7,14,28
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)
Measured: 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
Difference in respiratory function between SOC alone or with AR-301 at Days 7,14, and 28 as time on supplemental oxygen
Measured: Day 7, 14, and 28
Changes in baseline in SOFA score between Standard of Care alone or with AR301 at Days 7,14,28
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.
Measured: Day 7, 14, and 28
Duration of intubation with ventilation
Number of days with intubation with ventilation
Measured: 28 days
Duration mechanical ventilation if tracheostomy in place
Number of days of intubation with mechanical ventilation if tracheostomy in place
Measured: 28 days
Duration of stay in ICU
Number of days of stay in ICU
Measured: 28 days
Duration hospitalization
Number of days of hospitalization
Measured: 28 days
Duration antibiotic use.
Number of days on antibiotics
Measured: 28 days
Pharmacokinetic Analysis - (Cmax)
Pharmacokinetic analysis measuring Maximum Serum Concentration (Cmax)
Measured: 28 days
Pharmacokinetic Analysis - (AUC)
Pharmacokinetic analysis measuring Area Under the Curve (AUC)
Measured: 28 Days
Pharmacokinetic Analysis - (T1/2)
Pharmacokinetic analysis measuring time for half of the initial dose of study drug to be eliminated from the body (T1/2)
Measured: 28 Days
Pharmacokinetic Analysis - (Tmax)
Pharmacokinetic analysis measuring time at which Cmax is obtained (Tmax)
Measured: 28 Days
Pharmacokinetic Analysis (Blood levels of AR-301)
Blood levels of AR-301 in the patient over time during the study period.
Measured: 28 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2019
- Study start3 May 2019
- Primary completion28 Oct 2022
- Study completion28 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 174 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aridis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Hasan S Jafri, MD, FAAP, Study director, Aridis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03816956
- Sponsor's protocol ID
- AR-301-002
- Acronym
- AR-301-002
- Status last verified
- Jul 2023
- First submitted
- 21 Dec 2018
- Last updated
- 6 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03816956
- Acronym / sponsor ID
- AR-301-002 / AR-301-002
- Conditions
- Lung Infection, Pneumonia, Ventilator-Associated, Infection, Bacterial, Staphylococcus Aureus
- Keywords
- Staphylococcus aureus, S. aureus, monoclonal antibody, Aridis, VAP, ventilator acquired pneumonia, infection, pneumonia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 174 participants (actual)
- Lead sponsor
- Aridis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 3 May 2019 (actual)
- Primary completion
- 28 Oct 2022 (actual)
- Study completion
- 28 Oct 2022 (actual)
- First posted
- 25 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study treatment | Experimental | Drug: AR-301Investigational/ Interventional Product group: AR-301 (tosatoxumab) 20 mg/kg administered once intravenously on the day of randomization. |
| Placebo treatment | Placebo comparator | Other: PlaceboControl group: Placebo administered intravenously on the day of randomization. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AR-301Also: AR-301 (tosatoxumab)AR-301 (tosatoxumab) 20 mg/kg administered once intravenously the day of enrolment. | Drug | Study treatment |
| PlaceboPlacebo comparator | Other | Placebo treatment |
Primary outcome
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.
15 secondary outcomes
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
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
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
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
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
Duration of intubation with ventilation
Time frame: 28 days
Duration mechanical ventilation if tracheostomy in place
Time frame: 28 days
Duration of stay in ICU
Time frame: 28 days
Duration hospitalization
Time frame: 28 days
Duration antibiotic use.
Time frame: 28 days
Pharmacokinetic Analysis - (Cmax)
Time frame: 28 days
Pharmacokinetic Analysis - (AUC)
Time frame: 28 Days
Pharmacokinetic Analysis - (T1/2)
Time frame: 28 Days
Pharmacokinetic Analysis - (Tmax)
Time frame: 28 Days
Pharmacokinetic Analysis (Blood levels of AR-301)
Time frame: 28 Days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2023.
- Website of the SponsorLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Lung Infection
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
RecruitingObservational study
VIRal Pulmonary Infections in Older AGE
Viral Pulmonary Infections
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hasan S Jafri, MD, FAAP study director
Aridis Pharmaceuticals
45 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AR-301 in people with Lung Infection and Pneumonia, Ventilator-Associated, run by Aridis Pharmaceuticals, Inc. at 45 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in France, Georgia, Russia, Ukraine, Belarus and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A comparison of Clinical Cure Rates of standard of care (SOC) alone and SOC with AR-301 (time frame: 21 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2023.