Trial Outcomes & Findings for Study to Compare Lefamulin to Moxifloxacin (With or Without Linezolid) for the Treatment of Adults With Pneumonia (NCT NCT02559310)

Last Updated: 2019-10-23

Results Overview

ECR was defined as survival with improvement in at least 2 signs and symptoms of CABP (relative to baseline), no worsening of any CABP sign or symptom, and no use of concomitant antibiotics (other than adjunctive linezolid, as allowed by the study protocol) for the treatment of CABP through the ECR assessment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

551 participants

Primary outcome timeframe

ECR was assessed 96 +/- 24 hours after the first dose of study drug.

Results posted on

2019-10-23

Participant Flow

The study was designed to enroll adults with CABP that was severe enough to require a minimum of at least 3 days of IV treatment. Subjects with a PORT score of III, IV and V were eligible. The first subject was randomized in February 2016 and the last subject was randomized in April 2017.

Subjects who met inclusion criteria and did not meet exclusion criteria were randomly assigned to a treatment group. Administration of study drug was expected to occur as soon as possible after the diagnosis of CABP with all Screening/Baseline assessments expected to be completed within 24 hours before the first dose IV study drug.

Participant milestones

Participant milestones
Measure	Lefamulin Lefamulin 150 mg IV q12h with option to switch to 600 mg PO q12h after at least 6 doses of IV treatment. Linezolid placebo q12h was added at baseline for patients with suspected MRSA.	Moxifloxacin ± Linezolid Moxifloxacin 400 mg IV q24h with option to switch to 400 mg PO q24h after at least 6 doses of IV treatment. Linezolid 600 mg IV q12h was added at baseline for patients with suspected MRSA.
Overall Study STARTED	276	275
Overall Study COMPLETED	249	256
Overall Study NOT COMPLETED	27	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Lefamulin Lefamulin 150 mg IV q12h with option to switch to 600 mg PO q12h after at least 6 doses of IV treatment. Linezolid placebo q12h was added at baseline for patients with suspected MRSA.	Moxifloxacin ± Linezolid Moxifloxacin 400 mg IV q24h with option to switch to 400 mg PO q24h after at least 6 doses of IV treatment. Linezolid 600 mg IV q12h was added at baseline for patients with suspected MRSA.
Overall Study Death	4	3
Overall Study Lost to Follow-up	5	3
Overall Study Physician Decision	2	1
Overall Study Withdrawal by Subject	13	9
Overall Study Sponsor Decision	0	1
Overall Study Randomized but not treated	3	2

Baseline Characteristics

Study to Compare Lefamulin to Moxifloxacin (With or Without Linezolid) for the Treatment of Adults With Pneumonia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lefamulin n=276 Participants Lefamulin 150 mg IV q12h with option to switch to 600 mg PO q12h after at least 6 doses of IV treatment. Linezolid placebo q12h was added at baseline for patients with suspected MRSA.	Moxifloxacin ± Linezolid n=275 Participants Moxifloxacin 400 mg IV q24h with option to switch to 400 mg PO q24h after at least 6 doses of IV treatment. Linezolid 600 mg IV q12h was added at baseline for patients with suspected MRSA.	Total n=551 Participants Total of all reporting groups
Age, Continuous	61 Years STANDARD_DEVIATION 16.31 • n=5 Participants	59.6 Years STANDARD_DEVIATION 14.86 • n=7 Participants	60.3 Years STANDARD_DEVIATION 15.61 • n=5 Participants
Sex: Female, Male Female	170 Participants n=5 Participants	160 Participants n=7 Participants	330 Participants n=5 Participants
Sex: Female, Male Male	106 Participants n=5 Participants	115 Participants n=7 Participants	221 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	268 Participants n=5 Participants	265 Participants n=7 Participants	533 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	25 Participants n=5 Participants	20 Participants n=7 Participants	45 Participants n=5 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
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) White	239 Participants n=5 Participants	239 Participants n=7 Participants	478 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Argentina	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Romania	7 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Hungary	10 participants n=5 Participants	13 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Philippines	23 participants n=5 Participants	17 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Ukraine	55 participants n=5 Participants	61 participants n=7 Participants	116 participants n=5 Participants
Region of Enrollment Thailand	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Russia	8 participants n=5 Participants	13 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment Latvia	17 participants n=5 Participants	11 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Netherlands	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Brazil	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Poland	6 participants n=5 Participants	1 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment South Africa	12 participants n=5 Participants	15 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Georgia	25 participants n=5 Participants	29 participants n=7 Participants	54 participants n=5 Participants
Region of Enrollment Bulgaria	65 participants n=5 Participants	58 participants n=7 Participants	123 participants n=5 Participants
Region of Enrollment Serbia	30 participants n=5 Participants	27 participants n=7 Participants	57 participants n=5 Participants
Region of Enrollment Bosnia and Herzegovina	11 participants n=5 Participants	14 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Peru	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Pneumonia Outcomes Research Team (PORT) Risk Class II	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Pneumonia Outcomes Research Team (PORT) Risk Class III	196 Participants n=5 Participants	201 Participants n=7 Participants	397 Participants n=5 Participants
Pneumonia Outcomes Research Team (PORT) Risk Class IV	76 Participants n=5 Participants	70 Participants n=7 Participants	146 Participants n=5 Participants
Pneumonia Outcomes Research Team (PORT) Risk Class V	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
CURB-65 Score 0	24 Participants n=5 Participants	33 Participants n=7 Participants	57 Participants n=5 Participants
CURB-65 Score 1	130 Participants n=5 Participants	121 Participants n=7 Participants	251 Participants n=5 Participants
CURB-65 Score 2	98 Participants n=5 Participants	97 Participants n=7 Participants	195 Participants n=5 Participants
CURB-65 Score 3	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
CURB-65 Score 4	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
American Thoracic Society (ATS) Minor Severity Criteria	54 Participants n=5 Participants	48 Participants n=7 Participants	102 Participants n=5 Participants
Systemic inflammatory response syndrome (SIRS) Criteria	268 Participants n=5 Participants	267 Participants n=7 Participants	535 Participants n=5 Participants
Bacteremic	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Received Single Dose Short Acting Systemic Antibacterial within 72 hrs of Randomization	66 Participants n=5 Participants	66 Participants n=7 Participants	132 Participants n=5 Participants
Renal Status Severe Impairment (CrCl <30mL/min)	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Renal Status Moderate Impairment (CrCl 30-<60mL/min)	61 Participants n=5 Participants	62 Participants n=7 Participants	123 Participants n=5 Participants
Renal Status Mild Impairment (CrCl 60-<90mL/min)	89 Participants n=5 Participants	75 Participants n=7 Participants	164 Participants n=5 Participants
Renal Status Normal Function (CrCl >=90mL/min)	121 Participants n=5 Participants	134 Participants n=7 Participants	255 Participants n=5 Participants
Renal Status Missing renal status	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: ECR was assessed 96 +/- 24 hours after the first dose of study drug.

Population: Intent to Treat Analysis Set: All randomized subjects

Outcome measures

Outcome measures
Measure	Lefamulin n=276 Participants Lefamulin 150 mg IV q12h with option to switch to 600 mg PO q12h after at least 6 doses of IV treatment. Linezolid placebo q12h was added at baseline for patients with suspected MRSA.	Moxifloxacin ± Linezolid n=275 Participants Moxifloxacin 400 mg IV q24h with option to switch to 400 mg PO q24h after at least 6 doses of IV treatment. Linezolid 600 mg IV q12h was added at baseline for patients with suspected MRSA.
Early Clinical Response (ECR) Responder	241 Participants	248 Participants
Early Clinical Response (ECR) Non-Responder	29 Participants	21 Participants
Early Clinical Response (ECR) Indeterminate	6 Participants	6 Participants

SECONDARY outcome

Timeframe: IACR was assessed at the Test-of-Cure visit; 5-10 days after the last dose of study drug.

Population: Modified ITT population: All randomized subjects who received any amount of study drug.

IACR was defined as resolution or improvement of a subject's clinical signs and symptoms such that no additional antibacterial therapy was administered for the treatment of the current episode of CABP

Outcome measures

Outcome measures
Measure	Lefamulin n=273 Participants Lefamulin 150 mg IV q12h with option to switch to 600 mg PO q12h after at least 6 doses of IV treatment. Linezolid placebo q12h was added at baseline for patients with suspected MRSA.	Moxifloxacin ± Linezolid n=273 Participants Moxifloxacin 400 mg IV q24h with option to switch to 400 mg PO q24h after at least 6 doses of IV treatment. Linezolid 600 mg IV q12h was added at baseline for patients with suspected MRSA.
Investigator's Assessment of Clinical Response (IACR) Success	223 Participants	230 Participants
Investigator's Assessment of Clinical Response (IACR) Failure	43 Participants	40 Participants
Investigator's Assessment of Clinical Response (IACR) Indeterminate	7 Participants	3 Participants

SECONDARY outcome

Timeframe: IACR was assessed at the Test of Cure visit, 5 - 10 days after the last dose of study drug.

Population: Clinically Evaluable population: Subset of ITT population having met additional pre-defined criteria.

Outcome measures

Outcome measures
Measure	Lefamulin n=236 Participants Lefamulin 150 mg IV q12h with option to switch to 600 mg PO q12h after at least 6 doses of IV treatment. Linezolid placebo q12h was added at baseline for patients with suspected MRSA.	Moxifloxacin ± Linezolid n=245 Participants Moxifloxacin 400 mg IV q24h with option to switch to 400 mg PO q24h after at least 6 doses of IV treatment. Linezolid 600 mg IV q12h was added at baseline for patients with suspected MRSA.
Investigator's Assessment of Clinical Response (IACR) Success	205 Participants	219 Participants
Investigator's Assessment of Clinical Response (IACR) Failure	31 Participants	26 Participants

Adverse Events

Lefamulin

Serious events: 19 serious events

Other events: 39 other events

Deaths: 6 deaths

Moxifloxacin ± Linezolid

Serious events: 13 serious events

Other events: 46 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Lefamulin n=273 participants at risk Lefamulin 150 mg IV q12h with option to switch to 600 mg PO q12h after at least 6 doses of IV treatment. Linezolid placebo q12h was added at baseline for patients with suspected MRSA.	Moxifloxacin ± Linezolid n=273 participants at risk Moxifloxacin 400 mg IV q24h with option to switch to 400 mg PO q24h after at least 6 doses of IV treatment. Linezolid 600 mg IV q12h was added at baseline for patients with suspected MRSA.
Metabolism and nutrition disorders Hypokalaemia	2.9% 8/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.	2.2% 6/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.
Gastrointestinal disorders Nausea	2.9% 8/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.	2.2% 6/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.
Psychiatric disorders Insomnia	2.9% 8/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.	1.8% 5/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.
General disorders Infusion Site Pain	2.9% 8/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.	0.00% 0/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.
General disorders Infusion Site Phlebitis	2.2% 6/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.	1.1% 3/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.
Investigations Alanine Aminotransferase Increased	1.5% 4/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.	2.2% 6/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.
Gastrointestinal disorders Diarrhoea	0.73% 2/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.	7.7% 21/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.
Vascular disorders Hypertension	0.73% 2/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.	2.2% 6/273 • Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug). Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.

Additional Information

Jennifer Schranz, MD, Chief Medical Officer

Nabriva Therapeutics US, Inc.

Phone: 610-981-2842

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee All data from the study is confidential information. Sponsor has the right to publish first. Thereafter, PI may publish data from the study, but PI must submit the publication to Sponsor for review at least 60 days prior to publication. Sponsor may remove any confidential and/or proprietary information. If Sponsor's publication is not submitted within 12 months after the study, or if Sponsor decides not to publish, PI may publish the data, subject to Sponsor's rights in the agreement.
Publication restrictions are in place

Restriction type: OTHER