Trial Outcomes & Findings for Study of the Efficacy and Safety of MEDI4893 (NCT NCT02296320)

Last Updated: 2019-12-23

Results Overview

The EAC S aureus pneumonia was based on clinical, radiographic, and microbiologic criteria. Clinical criteria: 1 major criteria (PaO2/FiO2 ratio \< 240 mmHg maintained for at least 4 hours or decrease in PaO2/FiO2 by \>= 50 mmHg maintained for at least 4 hrs or a need to initiate non-invasive mechanical ventilation or re-initiate invasive mechanical ventilation because of respiratory failure or worsening of respiratory status); and at least 2 of minor criteria (systemic signs of infection, production of purulent sputum/endotracheal secretions, new onset of cough, physical examination findings consistent with pneumonia/pulmonary consolidation, dyspnea, and/or tachypnea). Radiographic criteria: new or worsening infiltrate consistent with pneumonia on chest X-ray obtained within 24 hrs of event. Microbiologic criteria: at least 1 culture positive for S aureus (respiratory specimen, or blood, or pleural fluid aspirate or lung tissue culture during episode of pneumonia).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

213 participants

Primary outcome timeframe

Day 1 through Day 31

Results posted on

2019-12-23

Participant Flow

The study was conducted between 10Oct2014 and 02Oct2018.

A total of 767 participants consented to participate in the study, of which 554 were screen failures. A total of 213 participants were randomized in the study.

Participant milestones

Participant milestones
Measure	Placebo Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg Participants received a single IV dose of MEDI4893 2000 milligrams (mg) on Day 1 of the study.	MEDI4893 5000 mg Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Overall Study STARTED	102	15	96
Overall Study Treated	100	15	96
Overall Study COMPLETED	67	10	59
Overall Study NOT COMPLETED	35	5	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg Participants received a single IV dose of MEDI4893 2000 milligrams (mg) on Day 1 of the study.	MEDI4893 5000 mg Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Overall Study Withdrawal by Subject	4	0	2
Overall Study Death	24	3	27
Overall Study Lost to Follow-up	5	2	7
Overall Study Not treated	2	0	0
Overall Study Not - specified	0	0	1

Baseline Characteristics

Study of the Efficacy and Safety of MEDI4893

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=100 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=15 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg n=96 Participants Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.	Total n=211 Participants Total of all reporting groups
Age, Continuous	55.7 Years STANDARD_DEVIATION 16.6 • n=5 Participants	52.5 Years STANDARD_DEVIATION 14.6 • n=7 Participants	57.7 Years STANDARD_DEVIATION 15.7 • n=5 Participants	56.4 Years STANDARD_DEVIATION 16.0 • n=4 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	5 Participants n=7 Participants	37 Participants n=5 Participants	87 Participants n=4 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	10 Participants n=7 Participants	59 Participants n=5 Participants	124 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	96 Participants n=5 Participants	15 Participants n=7 Participants	92 Participants n=5 Participants	203 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) White	97 Participants n=5 Participants	13 Participants n=7 Participants	94 Participants n=5 Participants	204 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 31

Population: An mITT population included all participants, who received any dose of study drug and analyzed according to their randomized treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=15 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg n=96 Participants Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Percentage of Participants With Endpoint Adjudication Committee-Determined (EAC) Staphylococcus Aureus (S Aureus) Pneumonia	26.0 Percentage of Participants	20.0 Percentage of Participants	17.7 Percentage of Participants

PRIMARY outcome

Timeframe: Day 1 through Day 31

Population: As-treated population included all participants, who received any dose of study drug and analyzed according to the treatment they actually received.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=15 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg n=96 Participants Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through 31 Days	90 Participants	15 Participants	87 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 91

Population: As-treated population included all participants, who received any dose of study drug and analyzed according to the treatment they actually received.

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=15 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg n=96 Participants Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Number of Participants With TEAEs Through 91 Days	92 Participants	15 Participants	89 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 191

Population: As-treated population included all participants, who received any dose of study drug and analyzed according to the treatment they actually received.

A serious adverse event (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. 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.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=15 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg n=96 Participants Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)	40 Participants	7 Participants	50 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 191

Population: As-treated population included all participants, who received any dose of study drug and analyzed according to the treatment they actually received.

An AESI is one of scientific and medical interest specific to understanding of the study drug and may have required close monitoring and rapid communication by the investigator to the sponsor. An AESI may have been serious or non-serious.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=15 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg n=96 Participants Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Number of Participants With Adverse Events of Special Interest (AESIs)	0 Participants	4 Participants	3 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 191

Population: As-treated population included all participants, who received any dose of study drug and analyzed according to the treatment they actually received.

An NOCD defined as a newly diagnosed medical condition that is of a chronic, ongoing nature. It is observed after receiving the study drug and is assessed by the investigator as medically significant.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=15 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg n=96 Participants Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Number of Participants With New Onset Chronic Diseases (NOCDs)	2 Participants	0 Participants	3 Participants

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 91

Population: An Intent-to-treat (ITT) population included all randomized participants and were analyzed according to their randomized treatment group. Participants who had quantifiable pharmacokinetic (PK) samples were analyzed for this outcome measure.

Maximum observed serum concentration (Cmax) of MEDI4893 is reported.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=94 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Maximum Observed Serum Concentration (Cmax) of MEDI4893	471.9 μg/mL Standard Deviation 123.0	1143.7 μg/mL Standard Deviation 375.6	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 91

Population: An ITT population included all randomized participants and were analyzed according to their randomized treatment group. Participants who had quantifiable PK samples were analyzed for this outcome measure.

Area under the serum concentration time curve from time zero to last measurable concentration (AUC\[0 - Last\]) of MEDI4893 is reported.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=94 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last]) of MEDI4893	9045.5 day*μg/mL Standard Deviation 5383.1	20127.5 day*μg/mL Standard Deviation 12852.2	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, and 30

Observed serum concentration of MEDI4893 through 30 days post dose (C30) is reported. Serum concentration of MEDI4893 through 30 days post dose accounted the overall concentration of MEDI4893 measured on specified time points (Days 1, 4, 8, 15, 22, and 30).

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=68 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Observed Serum Concentration of MEDI4893 Through 30 Days Post Dose (C30)	122.0 μg/mL Standard Deviation 65.0	295.9 μg/mL Standard Deviation 130.6	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 90

Observed serum concentration of MEDI4893 through 90 days post dose (C90) is reported. Serum concentration of MEDI4893 through 90 days post dose accounted the overall concentration of MEDI4893 measured on specified time points (Days 1, 4, 8, 15, 22, 31, 61, and 91).

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=54 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Observed Serum Concentration of MEDI4893 Through 90 Days Post Dose (C90)	71.5 μg/mL Standard Deviation 35.5	192.0 μg/mL Standard Deviation 84.0	—

SECONDARY outcome

Timeframe: Pre-dose on Day 1 (Baseline); and on Days 31, 61, and 91

Population: As-treated population included all participants, who received any dose of study drug and analyzed according to the treatment they actually received.

Participants with ADA-positive at any of Day 31, Day 61, or Day 91 post-baseline assessments were always counted as "positive" at post-baseline.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	MEDI4893 2000 mg n=15 Participants Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	MEDI4893 5000 mg n=96 Participants Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to MEDI4893 Positive at baseline; not detected post-baseline	0 Participants	0 Participants	1 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to MEDI4893 Positive at baseline	3 Participants	0 Participants	2 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to MEDI4893 Positive post-baseline	5 Participants	0 Participants	0 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to MEDI4893 Positive at baseline and post-baseline	2 Participants	0 Participants	0 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to MEDI4893 Not detected at baseline; positive post-baseline	3 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 40 serious events

Other events: 90 other events

Deaths: 24 deaths

MEDI4893 2000 mg

Serious events: 7 serious events

Other events: 15 other events

Deaths: 3 deaths

MEDI4893 5000 mg

Serious events: 50 serious events

Other events: 85 other events

Deaths: 27 deaths

Serious adverse events

Other adverse events

Additional Information

Hasan S. Jafri

MedImmune, LLC

Phone: 301-398-4431

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Medimmune has 60 days to review results communications prior to public release and may delete information that compromises on-going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Publication restrictions are in place

Restriction type: OTHER