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CompletedNCT02559310LEAPUpdated Oct 23, 2019Results posted

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

A Phase 3 interventional study of lefamulin and Moxifloxacin in Community Acquired Pneumonia, sponsored by Nabriva Therapeutics AG. Completed at 99 sites in 18 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-10-23.

Sponsored by Nabriva Therapeutics AG · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
551
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study evaluates the safety and efficacy of lefamulin, a pleuromutilin, for the treatment of adults with moderate to severe community-acquired bacterial pneumonia.

Read the detailed description

Lefamulin is a potent, semi-synthetic antibacterial belonging to a novel class known as the pleuromutilins. Both the intravenous (IV) and oral dosage forms of lefamulin are under investigation in this study. Lefamulin's in vitro antibacterial profile includes the most important bacterial pathogens causing respiratory tract infection (RTI). The antibacterial spectrum comprises S. pneumoniae, H. influenzae, M. catarrhalis, the atypical respiratory pathogens L. pneumophila, C. pneumoniae, and M. pneumoniae, S. aureus including MRSA and CA-MRSA, ß-haemolytic streptococci including S. pyogenes and S. agalactiae, and Enterococcus faecium including vancomycin-resistant enterococci (VRE). Moreover, as demonstrated in cross-resistance studies, lefamulin remains active against clinical isolates resistant to the following antimicrobial(s) (classes): macrolides, lincosamides, streptogramin B, oxazolidinones, tetracyclines, ß lactams, quinolones, trimethoprim-sulfametoxazole, mupirocin, and vancomycin.

02

Conditions studied

  • Community Acquired Pneumonia

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Keywords

  • Pneumonia
  • CABP
  • CAP
  • Community acquired bacterial pneumonia
03

In context

Pneumonia

2,044 studies on the registry are indexed under Pneumonia; 283 are open to participants now.

This study's enrollment of 551 is above the median of 106 across 1,247 interventional studies indexed under Pneumonia.

Browse Pneumonia studies →

Lead sponsor

Nabriva Therapeutics AG is the lead sponsor of 9 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Be male or female at least 18 years of age.
  2. Provide written informed consent and be willing and able to adhere to the study-specified procedures and restrictions.

  3. Have an acute illness (7 days duration) with at least 3 of the following symptoms consistent with a lower respiratory tract infection (new or worsening):

    • Dyspnea
    • New or increased cough
    • Purulent sputum production
    • Chest pain due to pneumonia

  4. Have at least 2 of the following vital sign abnormalities:

    • Fever (body temperature >38.0°C (100.4°F) measured orally or equivalent temperature from an alternate body site) or hypothermia (body temperature \<35.0°C (95.0°F) measured orally or equivalent temperature from an alternate body site)
    • Hypotension (systolic blood pressure \<90 mmHg)
    • Tachycardia (heart rate >100 beats/min)
    • Tachypnea (respiratory rate >20 breaths/min)

  5. Have at least 1 other clinical sign or laboratory finding of CABP:

    • Hypoxemia (i.e., O2 saturation \<90% on room air or while receiving supplemental oxygen at subject's baseline requirement or PaO2 \<60 mmHg)
    • Auscultatory and/or percussion findings consistent with pneumonia (e.g., crackles, egophony, dullness)
    • White blood cell (WBC) count >10,000 cells/mm3 or \<4500 cells/mm3 or >15% immature neutrophils (bands) regardless of total WBC count
  6. Have radiographically-documented pneumonia within 48 hours before enrollment (i.e., infiltrates in a lobar or multilobar distribution or diffuse opacities on chest x-ray or chest computed tomography scan consistent with acute bacterial pneumonia).
  7. Have a Pneumonia Outcomes Research Team (PORT) Risk Class ≥III.

Exclusion criteria

Exclusion Criteria:

  1. Have received more than a single dose of a short-acting oral or IV antibacterial for CABP within 72 hours before randomization
  2. Require concomitant systemic antibacterial therapy potentially effective against CABP pathogens
  3. Have been hospitalized for 2 or more days within 90 days prior to the onset of symptoms or have resided in a nursing home or long-term healthcare facility within 30 days prior to the onset of symptoms. NOTE: Residence in an independent living facility is permitted.
  4. Have confirmed or suspected CABP caused by a pathogen known to be resistant to any of the study drugs (e.g., Pseudomonas aeruginosa, any pathogen of the Enterobacteriaceae Family) or attributable to etiologies other than community acquired bacterial pathogens (e.g., ventilator associated pneumonia, hospital acquired bacterial pneumonia, bacterial aspiration pneumonia, Pneumocystis jiroveci pneumonia or other fungal pneumonia, viral or mycobacterial infection of the lung).
  5. Have a noninfectious cause of pulmonary infiltrates (e.g., pulmonary embolism, chemical pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure, bronchial obstruction, lung cancer, cystic fibrosis).
  6. Have confirmed or suspected pleural empyema (does not include sterile parapneumonic effusions).
  7. Require mechanical ventilation.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
551 participants (actual)

Study arms

  • Experimental
    Lefamulin

    Intravenous lefamulin with potential step-down to oral lefamulin

    Drug: lefamulin

  • Active comparator
    Moxifloxacin +/- Linezolid

    Intravenous moxifloxacin with potential step-down to oral moxifloxacin +/- linezolid

    Drug: Moxifloxacin · Drug: Linezolid

Interventions

  • Druglefamulin

    antibacterial agent

    Also known as: BC-3781

  • DrugMoxifloxacin

    antibacterial agent

    Also known as: Avelox

  • DrugLinezolid

    antibacterial agent

    Also known as: Zyvox

06

What researchers measure

Primary outcomes

  1. Early Clinical Response (ECR)

    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.

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

Secondary outcomes

  1. Investigator's Assessment of Clinical Response (IACR)

    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

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

  2. Investigator's Assessment of Clinical Response (IACR)

    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.

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

07

Results

Posted Oct 23, 2019

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.

Participant flow — Overall Study
MilestoneLefamulinMoxifloxacin ± Linezolid
Started276275
Completed249256
Not completed2719
Withdrew: Death43
Withdrew: Lost to follow-up53
Withdrew: Physician decision21
Withdrew: Withdrawal by subject139
Withdrew: Sponsor decision01
Withdrew: Randomized but not treated32

Outcome measures

PrimaryEarly Clinical Response (ECR)

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.

Time frame:
ECR was assessed 96 +/- 24 hours after the first dose of study drug.
Reported as:
Count of participants · Participants
Early Clinical Response (ECR)
ParticipantsLefamulinMoxifloxacin ± Linezolid
Responder241248
Non-Responder2921
Indeterminate66
Statistical analysis
  • Lefamulin vs Moxifloxacin ± Linezolid · Treatment difference (lef - mox): -2.9 · 95% CI -8.5 to 2.8Difference in percentage of Responders for ECR (Lefamulin - Moxifloxacin). CI computed using continuity-corrected Z-statistic.
SecondaryInvestigator's Assessment of Clinical Response (IACR)

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

Time frame:
IACR was assessed at the Test-of-Cure visit; 5-10 days after the last dose of study drug.
Reported as:
Count of participants · Participants
Investigator's Assessment of Clinical Response (IACR)
ParticipantsLefamulinMoxifloxacin ± Linezolid
Success223230
Failure4340
Indeterminate73
Statistical analysis
  • Lefamulin vs Moxifloxacin ± Linezolid · Treatment difference (lef - mox): -2.6 · 95% CI -8.9 to 3.9Difference in Percentage of Success for IACR at test of cure visit (Lefamulin - Moxifloxacin). CI computed via Miettinen-Nurminen method, adjusted for prior antibiotic use \[Y vs. N\] and PORT risk class \[III vs. IV/V\], using CMH stratum weights.
  • Lefamulin · Treatment difference (lef - mox): -2.6 · 95% CI -9.2 to 4.1Difference in percentage of Success for IACR at test of cure visit. CI computed using continuity-corrected Z-statistic.
SecondaryInvestigator's Assessment of Clinical Response (IACR)

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.

Time frame:
IACR was assessed at the Test of Cure visit, 5 - 10 days after the last dose of study drug.
Reported as:
Count of participants · Participants
Investigator's Assessment of Clinical Response (IACR)
ParticipantsLefamulinMoxifloxacin ± Linezolid
Success205219
Failure3126
Statistical analysis
  • Lefamulin vs Moxifloxacin ± Linezolid · Treatment difference: -2.5 · 95% CI -8.4 to 3.4Difference in percentage of success for IACR at test of cure visit (Lefamulin - Moxifloxacin). CI computed via Miettinen-Nurminen method, adjusted for prior antibiotic use \[Y vs. N\] and PORT risk class \[III vs. IV/V\], using CMH stratum weights.
  • Lefamulin vs Moxifloxacin ± Linezolid · Treatment difference (lef - mox): -2.5 · 95% CI -8.7 to 3.7Difference in Percentage of Success for IACR at test of cure visit (Lefamulin - Moxifloxacin). CI computed using continuity-corrected Z-statistic

Adverse events

Collected over 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).. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Lefamulin6/273 (2.2%)19/273 (7%)39/273 (14.3%)
Moxifloxacin ± Linezolid5/273 (1.8%)13/273 (4.8%)46/273 (16.8%)
Most frequent serious events
Showing 10 of 34
Most frequent serious events
EventLefamulinMoxifloxacin ± Linezolid
PneumoniaInfections and infestations4/2731/273
Acute Myocardial InfarctionCardiac disorders0/2731/273
Atrial FibrillationCardiac disorders1/2730/273
Cardiac ArrestCardiac disorders0/2731/273
Cardiac Failure CongestiveCardiac disorders1/2730/273
Cardiogenic ShockCardiac disorders0/2731/273
Myocardial InfarctionCardiac disorders1/2730/273
Myocardial IschaemiaCardiac disorders0/2731/273
Ventricular ArrhythmiaCardiac disorders1/2730/273
HaematemesisGastrointestinal disorders0/2731/273
Most frequent other events
Most frequent other events
EventLefamulinMoxifloxacin ± Linezolid
DiarrhoeaGastrointestinal disorders2/27321/273
HypokalaemiaMetabolism and nutrition disorders8/2736/273
NauseaGastrointestinal disorders8/2736/273
InsomniaPsychiatric disorders8/2735/273
Infusion Site PainGeneral disorders8/2730/273
Infusion Site PhlebitisGeneral disorders6/2733/273
Alanine Aminotransferase IncreasedInvestigations4/2736/273
HypertensionVascular disorders2/2736/273

Baseline characteristics

Intent-to-Treat (ITT) Analysis Set

Age, Continuous
Age, Continuous(Years)LefamulinMoxifloxacin ± LinezolidTotal
Mean61 ± 16.3159.6 ± 14.8660.3 ± 15.61
Sex: Female, Male
Sex: Female, Male(Participants)LefamulinMoxifloxacin ± LinezolidTotal
Female170160330
Male106115221
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)LefamulinMoxifloxacin ± LinezolidTotal
Hispanic or Latino81018
Not Hispanic or Latino268265533
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)LefamulinMoxifloxacin ± LinezolidTotal
American Indian or Alaska Native011
Asian252045
Native Hawaiian or Other Pacific Islander000
Black or African American111223
White239239478
More than one race134
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)LefamulinMoxifloxacin ± LinezolidTotal
Argentina369
Romania7411
Hungary101323
United States213
Philippines231740
Ukraine5561116
Thailand011
Russia81321
Latvia171128
Netherlands101
Brazil011
Poland617
South Africa121527
Georgia252954
Bulgaria6558123
Serbia302757
Bosnia and Herzegovina111425
Peru134
Pneumonia Outcomes Research Team (PORT) Risk Class
Pneumonia Outcomes Research Team (PORT) Risk Class(Participants)LefamulinMoxifloxacin ± LinezolidTotal
II011
III196201397
IV7670146
V437
CURB-65 Score
CURB-65 Score(Participants)LefamulinMoxifloxacin ± LinezolidTotal
0243357
1130121251
29897195
3222244
4224
American Thoracic Society (ATS) Minor Severity Criteria
American Thoracic Society (ATS) Minor Severity Criteria(Participants)LefamulinMoxifloxacin ± LinezolidTotal
Count of participants5448102

4 further baseline measures are reported on the registry.

08

Study locations

99 sites
  • Site 1006
    Hazard, Kentucky 41701, United States
  • Site 1008
    Shreveport, Louisiana 71103, United States
  • Site 1005
    Minneapolis, Minnesota 55415, United States
  • Site 1001
    Butte, Montana 59701, United States
  • Site 1009
    Akron, Ohio 44309, United States
  • Site 1002
    Dayton, Ohio 45402, United States
  • Site 1004
    Splendora, Texas 77372, United States
  • Site 3005
    La Plata, Buenos Aires 1900, Argentina
  • Site 3006
    Rosario, Santa Fe S2000CVB, Argentina
  • Site 3004
    Cordoba, X5016KEH, Argentina
  • Site 3003
    Córdoba, X5000EPU, Argentina
  • Site 3007
    Córdoba, X5000JRD, Argentina
  • Site 3001
    Córdoba, X5004CDT, Argentina
  • Site 4003
    Mostar, 88000, Bosnia and Herzegovina
  • Site 4001
    Tuzla, 75000, Bosnia and Herzegovina
  • Site 4004
    Zenica, 72000, Bosnia and Herzegovina
  • Site 3104
    Belo Horizonte, Minas Gerais 30150-221, Brazil
  • Site 3102
    Passo Fundo, Rio Grande Do Sol 99010-080, Brazil
  • Site 3103
    Campinas, Sao Paulo 13059-900, Brazil
  • Site 3101
    Sao Paulo Do Rio Preto, Sao Paulo 15090-000, Brazil
  • Site 4105
    Gabrovo, 5300, Bulgaria
  • Site 4107
    Lovech, 5500, Bulgaria
  • Site 4112
    Pernik, 2300, Bulgaria
  • Site 4103
    Ruse, 7002, Bulgaria
  • Site 4108
    Smolyan, 4700, Bulgaria
  • Site 4102
    Sofia, 1202, Bulgaria
  • Site 4101
    Sofia, 1233, Bulgaria
  • Site 4106
    Sofia, 1233, Bulgaria
  • Site 4110
    Sofia, 1606, Bulgaria
  • Site 4111
    Sofia, 1606, Bulgaria
  • Site 4104
    Veliko Tarnovo, 5000, Bulgaria
  • Site 4109
    Vidin, 3700, Bulgaria
  • Site 4206
    Tbilisi, 0101, Georgia
  • Site 4204
    Tbilisi, 0144, Georgia
  • Site 4205
    Tbilisi, 0144, Georgia
  • Site 4201
    Tbilisi, 0159, Georgia
  • Site 4202
    Tbilisi, 0186, Georgia
  • Site 4305
    Budapest, 1121, Hungary
  • Site 4306
    Csorna, 9300, Hungary
  • Site 4304
    Debrecen, 4043, Hungary
  • Site 4302
    Farkasgyepű, 8582, Hungary
  • Site 4307
    Miskolc, 3529, Hungary
  • Site 4308
    Miskolc, 3529, Hungary
  • Site 4303
    Törökbálint, 2045, Hungary
  • Site 4403
    Daugavpils, LV-5417, Latvia
  • Site 4401
    Liepaja, LV-3414, Latvia
  • Site 4402
    Riga, LV-1038, Latvia
  • Site 4603
    Almelo, Overijssel 7609 PP, Netherlands
  • Site 4602
    Helmond, 5707 HA, Netherlands
  • Site 3205
    Trujillo, La Libertad, Peru
  • Site 3202
    Lima, Lima 18, Peru
  • Site 3204
    Lima, Lima 1, Peru
  • Site 3201
    Lima, Lima 29, Peru
  • Site 2005
    Iloilo City, 5000, Philippines
  • Site 2003
    Manila City, 1000, Philippines
  • Site 2004
    Manila, 1012, Philippines
  • Site 2002
    Quezon City, 1100, Philippines
  • Site 2001
    Quezon City, 1114, Philippines
  • Site 4703
    Skierniewice, Lódzkie 96-100, Poland
  • Site 4704
    Warszawa, Mazowieckie 02-097, Poland
  • Site 4701
    Lódz, 90-153, Poland
  • Site 4702
    Wilkowice, 43-365, Poland
  • Site 4802
    Palazu Mare, Constanta 900002, Romania
  • Site 4801
    Bucharest, 21105, Romania
  • Site 4806
    Bucharest, 21105, Romania
  • Site 4810
    Bucuresti, 030303, Romania
  • Site 4811
    Cluj-Napoca, 040000, Romania
  • Site 4803
    Craiova, 200515, Romania
  • Site 4808
    Craiova, 200515, Romania
  • Site 4807
    Timisoara, 300310, Romania
  • Site 4809
    Timisoara, 300310, Romania
  • Site 4904
    Chelyabinsk, 454021, Russian Federation
  • Site 4902
    Novosibirsk, 630102, Russian Federation
  • Site 4906
    Smolensk, 214019, Russian Federation
  • Site 4903
    St. Petersburg, 191163, Russian Federation
  • Site 4901
    St. Petersburg, 197706, Russian Federation
  • Site 4905
    Yaroslavl, 150062, Russian Federation
  • Site 5003
    Nis, Nišavski Okrug 18204, Serbia
  • Site 5002
    Belgrade, 11000, Serbia
  • Site 5004
    Sremska Kamenica, 11080, Serbia
  • Site 5001
    Kragujevac, Šumadijski Okrug 34000, Serbia
  • Site 5103
    Benoni, Gauteng 1500, South Africa
  • Site 5104
    Pretoria, Gauteng 181, South Africa
  • Site 5105
    Thabazimbi, Limpopo 380, South Africa
  • Site 5101
    Middelburg, Mpumalanga 1050, South Africa
  • Site 5102
    Krugersdorp, 1724, South Africa
  • Site 2103
    Nonthaburi, 10110, Thailand
  • Site 5203
    Chernivtsi, Chernivets'ka Oblast 58005, Ukraine
  • Site 5204
    Ivano-Frankivsk, Ivano-Frankivs'ka Oblast 76018, Ukraine
  • Site 5201
    Kharkiv, Kharkivs'ka Oblast 61124, Ukraine
  • Site 5209
    Kherson, Khersons'ka Oblast 73000, Ukraine
  • Site 5211
    Odesa, Odes'ka Oblast 65025, Ukraine
  • Site 5210
    Zaporizhzhia, Zaporiz'ka Oblast 69118, Ukraine
  • Site 5202
    Kyiv, 01133, Ukraine
  • Site 5205
    Kyiv, 03680, Ukraine
  • Site 5207
    Kyïv, 03680, Ukraine
  • Site 5208
    Sumy, 40022, Ukraine
  • Site 5212
    Zaporizhzhia, 69035, Ukraine
  • Site 5206
    Zhytomyr, 10002, Ukraine
09

References and documents

Publications

  • File TM Jr, Alexander E, Goldberg L, Das AF, Sandrock C, Paukner S, Moran GJ. Lefamulin efficacy and safety in a pooled phase 3 clinical trial population with community-acquired bacterial pneumonia and common clinical comorbidities. BMC Pulm Med. 2021 May 8;21(1):154. doi: 10.1186/s12890-021-01472-z. PubMed 33964925 ↗
  • File TM, Goldberg L, Das A, Sweeney C, Saviski J, Gelone SP, Seltzer E, Paukner S, Wicha WW, Talbot GH, Gasink LB. Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial. Clin Infect Dis. 2019 Nov 13;69(11):1856-1867. doi: 10.1093/cid/ciz090. Erratum In: Clin Infect Dis. 2020 May 23;70(11):2459. doi: 10.1093/cid/ciz710. PubMed 30722059 ↗

Study documents

  • Statistical analysis plan · Aug 30, 2017
  • Study protocol · Mar 15, 2016

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 23, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02559310
Lead sponsor
Nabriva Therapeutics AG
Responsible party
Sponsor
First posted
Sep 24, 2015
Start date
Sep 2015
Primary completion
Apr 2017
Completion
May 2017
Results posted
Oct 23, 2019
Last update
Oct 23, 2019

Study contacts

Jennifer Schranz, MD
study chair · Nabriva Therapeutics

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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