Pseudomonas Aeruginosa
Conditions
Keywords
Pseudomonas aeruginosa, Pneumonia
Brief summary
Clinical trial looking to evaluate the efficacy and safety of MEDI3902 in mechanically ventilated participants for the prevention of nosocomial pneumonia caused by Pseudomonas aeruginosa.
Interventions
DRUGMEDI3902
Participants will receive a single IV dose of MEDI3902 500 mg and 1500 mg in MEDI3902 500 mg arm and MEDI3902 1500 mg arm, respectively.
OTHERPlacebo
Participants will receive a single IV dose of placebo matched to MEDI3902.
Sponsors
Innovative Medicines Initiative
Antibacterial Resistance Leadership Group
National Institute of Allergy and Infectious Diseases (NIAID)
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Colonized with P aeruginosa, expected to require prolonged intubation and mechanical ventilation, without any evidence of active pneumonia.
Exclusion criteria
P aeruginosa disease at randomisation; lung injury score consistent with pneumonia; current lung disease; currently receiving protocol-specified Anti-P aeruginosa antibiotics, moribund participants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa | Day 1 through Day 22 | Percentage of participants with nosocomial pneumonia caused by Pseudomonas aeruginosa is reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Day 1 through Day 50 | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. |
| Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | Day 1 through Day 50 | An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI) | Day 1 through Day 50 | An AESI is one of scientific and medical interest specific event for understanding of the study drug and may require close monitoring and rapid communication by the investigator to the sponsor. An AESI may be serious or non-serious. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Elimination Half-life (t1/2) of MEDI3902 | Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50 | The t1/2 of MEDI3902 is reported. |
| Maximum Observed Concentration (Cmax) of MEDI3902 | Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50 | The Cmax of MEDI3902 is reported. |
| Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment | Day 1 (predose), Day 15, Day 29, Day 50 | Number of participants with positive ADA to MEDI3902 treatment is reported. Persistent positive is defined as positive at \>= 2 post-baseline assessments or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at \>= 2 post-baseline assessments. |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3902 | Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50 | The AUC0-inf of MEDI3902 is reported. |
| Clearance (CL) of MEDI3902 | Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50 | The CL of MEDI3902 from body after intrevanous administration of single dose is reported. |
| Percentage of Participants Maintaining MEDI3902 Serum Levels Above the Target Level (1.7 µg/mL) Through 21 Days Post Dose | Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, and Day 22 | Percentage of participants maintaining MEDI3902 serum levels above the target level (1.7 µg/mL) through 21 days post dose is reported. |
Countries
Austria, Belgium, Croatia, Czechia, France, Greece, Hungary, Ireland, Israel, Portugal, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A total of 188 participants were assigned to the study treatment groups. Out of 188 participants, 4 participants did not receive the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Of the 85 participants, 83 participants received single intravenous (IV) dose of placebo matched to MEDI3902. | 85 |
| MEDI3902 500 mg Participants received single IV dose of 500 mg MEDI3902. | 16 |
| MEDI3902 1500 mg Of the 87 participants, 85 participants received single IV dose of 1500 mg MEDI3902. | 87 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 19 | 3 | 24 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Participant not eligible (negative PCR) | 0 | 0 | 1 |
| Overall Study | Participant not fit post-randomization | 0 | 0 | 1 |
| Overall Study | Principal investigator's decision | 1 | 0 | 0 |
| Overall Study | Sponsor's decision | 1 | 0 | 0 |
| Overall Study | Transferred to other hospital | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | MEDI3902 500 mg | MEDI3902 1500 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 64.4 Years STANDARD_DEVIATION 13 | 62.7 Years STANDARD_DEVIATION 9.3 | 60.6 Years STANDARD_DEVIATION 15.1 | 62.5 Years STANDARD_DEVIATION 13.8 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 0 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 77 Participants | 16 Participants | 83 Participants | 176 Participants |
| Sex: Female, Male Female | 22 Participants | 6 Participants | 32 Participants | 60 Participants |
| Sex: Female, Male Male | 63 Participants | 10 Participants | 55 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 19 / 83 | 3 / 16 | 24 / 85 |
| other Total, other adverse events | 79 / 83 | 15 / 16 | 82 / 85 |
| serious Total, serious adverse events | 35 / 83 | 4 / 16 | 38 / 85 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI)
An AESI is one of scientific and medical interest specific event for understanding of the study drug and may require close monitoring and rapid communication by the investigator to the sponsor. An AESI may be serious or non-serious.
Time frame: Day 1 through Day 50
Population: The As-treated population is all treated participants, grouped according to actual treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI) | 1 Participants |
| MEDI3902 500 mg | Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI) | 0 Participants |
| MEDI3902 1500 mg | Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI) | 2 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time frame: Day 1 through Day 50
Population: The As-treated population is all treated participants, grouped according to actual treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 81 Participants |
| MEDI3902 500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 15 Participants |
| MEDI3902 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 84 Participants |
Primary
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Day 1 through Day 50
Population: The As-treated population is all treated participants, grouped according to actual treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 35 Participants |
| MEDI3902 500 mg | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 4 Participants |
| MEDI3902 1500 mg | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 38 Participants |
Primary
Percentage of Participants With Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa
Percentage of participants with nosocomial pneumonia caused by Pseudomonas aeruginosa is reported.
Time frame: Day 1 through Day 22
Population: The modified intent to treat (mITT) population included all randomized and treated participants, grouped according to assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa | 18.1 Percentage of participants |
| MEDI3902 500 mg | Percentage of Participants With Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa | 12.5 Percentage of participants |
| MEDI3902 1500 mg | Percentage of Participants With Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa | 22.4 Percentage of participants |
p-value: 0.49180% CI: [-83.8, 16.8]Poisson regression with robust variance
Secondary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3902
The AUC0-inf of MEDI3902 is reported.
Time frame: Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50
Population: The As-treated population is all treated participants, grouped according to actual treatment received. Number of participants analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3902 | 440 day*mcg/mL | Standard Deviation 135 |
| MEDI3902 500 mg | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3902 | 1510 day*mcg/mL | Standard Deviation 675 |
Secondary
Clearance (CL) of MEDI3902
The CL of MEDI3902 from body after intrevanous administration of single dose is reported.
Time frame: Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50
Population: The As-treated population is all treated participants, grouped according to actual treatment received. Number of participants analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clearance (CL) of MEDI3902 | 1.31 L/day | Standard Deviation 0.638 |
| MEDI3902 500 mg | Clearance (CL) of MEDI3902 | 1.27 L/day | Standard Deviation 0.86 |
Secondary
Maximum Observed Concentration (Cmax) of MEDI3902
The Cmax of MEDI3902 is reported.
Time frame: Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50
Population: The As-treated population is all treated participants, grouped according to actual treatment received. Number of Subjects Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Concentration (Cmax) of MEDI3902 | 87.6 mcg/mL | Standard Deviation 23.9 |
| MEDI3902 500 mg | Maximum Observed Concentration (Cmax) of MEDI3902 | 299 mcg/mL | Standard Deviation 94.1 |
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment
Number of participants with positive ADA to MEDI3902 treatment is reported. Persistent positive is defined as positive at \>= 2 post-baseline assessments or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at \>= 2 post-baseline assessments.
Time frame: Day 1 (predose), Day 15, Day 29, Day 50
Population: The As-treated population is all treated participants, grouped according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment | Transient positive | 2 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment | Persistent positive | 4 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment | Positive at baseline and post-baseline | 3 Participants |
| MEDI3902 500 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment | Transient positive | 2 Participants |
| MEDI3902 500 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment | Positive at baseline and post-baseline | 2 Participants |
| MEDI3902 500 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment | Persistent positive | 2 Participants |
| MEDI3902 1500 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment | Persistent positive | 4 Participants |
| MEDI3902 1500 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment | Positive at baseline and post-baseline | 1 Participants |
| MEDI3902 1500 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment | Transient positive | 8 Participants |
Secondary
Percentage of Participants Maintaining MEDI3902 Serum Levels Above the Target Level (1.7 µg/mL) Through 21 Days Post Dose
Percentage of participants maintaining MEDI3902 serum levels above the target level (1.7 µg/mL) through 21 days post dose is reported.
Time frame: Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, and Day 22
Population: The As-treated population is all treated participants, grouped according to actual treatment received. Number of participants analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Maintaining MEDI3902 Serum Levels Above the Target Level (1.7 µg/mL) Through 21 Days Post Dose | 50 Percentage of participants |
| MEDI3902 500 mg | Percentage of Participants Maintaining MEDI3902 Serum Levels Above the Target Level (1.7 µg/mL) Through 21 Days Post Dose | 80.6 Percentage of participants |
Secondary
Terminal Elimination Half-life (t1/2) of MEDI3902
The t1/2 of MEDI3902 is reported.
Time frame: Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50
Population: The As-treated population is all treated participants, grouped according to actual treatment received. Number of participants analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Elimination Half-life (t1/2) of MEDI3902 | 6.56 day | Standard Deviation 4.03 |
| MEDI3902 500 mg | Terminal Elimination Half-life (t1/2) of MEDI3902 | 5.65 day | Standard Deviation 2.69 |