Study to Compare Lefamulin to Moxifloxacin for the Treatment of Adults With Pneumonia (LEAP2)

A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Oral Lefamulin (BC 3781) Versus Oral Moxifloxacin in Adults With Community-Acquired Bacterial Pneumonia

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

Study Overview

• Status: Completed
• Conditions: Community Acquired Pneumonia
• Intervention / Treatment: Drug: lefamulin; Drug: Moxifloxacin

Detailed Description

Lefamulin is a potent, semi-synthetic antibacterial belonging to a novel class known as the pleuromutilins. The oral dosage form of lefamulin is 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.

• Study Type: Interventional
• Enrollment (Actual): 738
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires AV, Argentina
    • Site 3059
  • Ciudad Autónoma de Buenos Aires, Argentina
    • Site 3056
  • Cordoba, Argentina, X5000EPU
    • Site 3054
  • Cordoba, Argentina
    • Site 3052
  • Cordoba, Argentina
    • Site 3057
  • General Pacheco, Argentina
    • Site 3058
  • La Plata, Argentina
    • Site 3051
  • La Plata, Argentina
    • Site 3053
• Brazil
  • Belo Horizonte, Brazil, 30150-221
    • Site 3154
  • Passo Fundo, Brazil, 99010-080
    • Site 3153
  • Sao Jose do Rio Preto, Brazil, 15090-000
    • Site 3152
• Bulgaria
  • Ruse, Bulgaria, 7002
    • 4162
  • Sliven, Bulgaria, 8800
    • Site 4154
  • Sofia, Bulgaria, 1233
    • Site 4160
  • Sofia, Bulgaria, 1336
    • Site 4157
  • Sofia, Bulgaria, 1606
    • Site 4153
  • Sofia, Bulgaria, 1606
    • Site 4156
  • Sofia, Bulgaria, 1680
    • Site 4161
  • Sofia, Bulgaria
    • 4163
  • Sofia, Bulgaria
    • 4164
  • Sofia, Bulgaria
    • 4165
  • Stara Zagora, Bulgaria, 6000
    • Site 4158
  • Vidin, Bulgaria, 3700
    • Site 4159
  • Vratsa, Bulgaria, 3000
    • Site 4152
• Chile
  • Santiago, Chile
    • Site 3353
  • Santiago, Chile
    • Site 3356
  • Santiago, Chile
    • Site 3357
  • Talca, Chile
    • Site 3354
  • Temuco, Chile
    • Site 3352
  • Valdivia, Chile
    • Site 3355
• Georgia
  • Batumi, Georgia
    • Site 4256
  • Tbilisi, Georgia, 101
    • Site 4253
  • Tbilisi, Georgia, 159
    • Site 4255
  • Tbilisi, Georgia, 179
    • Site 4252
  • Tbilisi, Georgia, 186
    • Site 4254
• Hungary
  • Budapest, Hungary, 1122
    • Site 4354
  • Budapest, Hungary, 1134
    • Site 4353
  • Matrahaza, Hungary, 3233
    • Site 4352
  • Torokbalint, Hungary, 2045
    • Site 4351
• Korea, Republic of
  • Bucheon-si, Korea, Republic of, 14647
    • Site 2257
  • Daegu, Korea, Republic of, 42415
    • Site 2253
  • Seoul, Korea, Republic of, 143-914
    • Site 2255
  • Seoul, Korea, Republic of, 152-703
    • Site 2256
  • Seoul, Korea, Republic of, 2259
    • Site 2251
  • Seoul, Korea, Republic of, 7985
    • Site 2252
  • Gyeonggi-do
    • Uijeongbu Si, Gyeonggi-do, Korea, Republic of, 11765
      • Site 2254
• Latvia
  • Liepāja, Latvia, LV3414
    • Site 4451
  • Rīga, Latvia, LV-1002
    • Site 4453
  • Valmiera, Latvia, LV 4201
    • Site 4452
• Mexico
  • Aguascalientes, Mexico, 20230
    • Site 1153
  • Guadalajara, Mexico, 44280
    • Site 1154
  • Monterrey, Mexico, 64460
    • Site 1151
  • Toluca, Mexico, 52140
    • Site 1152
• Peru
  • Arequipa, Peru
    • Site 3262
  • Cusco, Peru
    • Site 3263
  • Cuzco, Peru
    • Site 3261
  • Ica, Peru
    • Site 3254
  • Iquitos, Peru
    • Site 3259
  • La Libertad, Peru
    • Site 3251
  • Lima, Peru
    • Site 3252
  • Lima, Peru
    • Site 3253
  • Lima, Peru
    • Site 3255
  • Lima, Peru
    • Site 3257
  • Lima, Peru
    • Site 3260
  • Lima, Peru
    • Site 3265
  • Lima Lima, Peru
    • Site 3258
  • Piura, Peru
    • Site 3256
  • Lima
    • Grau, Lima, Peru
      • Site 3264
• Philippines
  • Caloocan City, Philippines, 1400
    • Site 2053
  • Cebu, Philippines, 6000
    • Site 2055
  • Iloilo City, Philippines, 5000
    • Site 2052
  • Quezon, Philippines, 1109
    • Site 2054
  • Quezon City, Philippines, 1100
    • Site 2056
  • Quezon City, Philippines
    • Site 2051
• Poland
  • Bochnia, Poland, 32-700
    • Site 4755
  • Chodziez, Poland, 64-800
    • Site 4754
  • Krakow, Poland, 31-011
    • Site 4753
  • Kraków, Poland, 31-202
    • Site 4756
  • Siedlce, Poland, 08-110
    • Site 4757
• Romania
  • Bucuresti, Romania, 21659
    • Site 4858
  • Bucureşti, Romania, 21105
    • Site 4855
  • Bucureşti, Romania, 30303
    • Site 4854
  • Cluj-Napoca, Romania, 400371
    • Site 4853
  • Codlea, Romania, 505100
    • Site 4851
  • Craiova, Romania, 200515
    • Site 4857
  • Timisoara, Romania, 300310
    • Site 4856
• Russian Federation
  • Barnaul, Russian Federation, 656045
    • Site 4953
  • Moscow, Russian Federation, 117913
    • Site 4957
  • Moscow, Russian Federation, 119192
    • Site 4952
  • Novosibirsk, Russian Federation, 6300
    • Site 4954
  • Saratov, Russian Federation, 410053
    • Site 4959
  • Smolensk, Russian Federation, 214019
    • Site 4958
  • St. Petersburg, Russian Federation, 1962
    • Site 4955
  • St. Petersburg, Russian Federation, 198205
    • Site 4951
• Serbia
  • Belgrade, Serbia, 11000
    • Site 5052
  • Belgrade, Serbia, 11000
    • Site 5056
  • Belgrade, Serbia, 11080
    • Site 5051
  • Belgrade, Serbia
    • 5057
  • Knez Selo, Serbia, 1820
    • Site 5055
  • Kragujevac, Serbia, 34000
    • Site 5054
  • Sremska Kamenica, Serbia, 21204
    • Site 5053
• South Africa
  • Bloemfontein, South Africa, 9301
    • Site 5151
  • Krugersdorp, South Africa, 1739
    • Site 5154
  • Middelburg, South Africa, 1050
    • Site 5155
  • Pretoria, South Africa
    • Site 5156
  • Queenswood, South Africa, 186
    • Site 5152
  • Witbank, South Africa, 1035
    • Site 5153
• Spain
  • Alicante, Spain, 3203
    • Site 4554
  • Badalona, Spain, 8916
    • Site 4556
  • Barcelona, Spain, 8003
    • Site 4552
  • Barcelona, Spain, 8035
    • Site 4555
  • Madrid, Spain, 28040
    • Site 4553
  • Madrid, Spain, 28046
    • Site 4551
• Taiwan
  • Kaohsiung, Taiwan, 82445
    • Site 2352
  • Kaohsiung, Taiwan
    • Site 2351
  • Taipei, Taiwan
    • Site 2354
• Ukraine
  • Chernivtsi, Ukraine, 58001
    • Site 5264
  • Ivano-Frankivs'k, Ukraine, 76018
    • Site 5261
  • Ivano-Frankivs'k, Ukraine, 7601
    • Site 5258
  • Kharkiv, Ukraine, 61124
    • Site 5256
  • Kharkiv, Ukraine, 61157
    • Site 5254
  • Kherson, Ukraine, 73000
    • Site 5255
  • Kyiv, Ukraine, 1133
    • Site 5263
  • Kyiv, Ukraine, 2091
    • SIte 5252
  • Kyiv, Ukraine, 3680
    • Site 5251
  • Kyiv, Ukraine, 3680
    • Site 5265
  • Poltava, Ukraine, 3603
    • Site 5259
  • Vinnytsya, Ukraine, 21029
    • Site 5260
  • Zaporizhzhya, Ukraine, 69035
    • Site 5253
  • Zaporizhzhya, Ukraine, 69065
    • Site 5257
• United States
  • California
    • Beverly Hills, California, United States
      • 1080
    • Fresno, California, United States, 93701
      • Site 1065
    • Northridge, California, United States
      • 1078
    • Oxnard, California, United States, 93030
      • Site 1072
    • Sacramento, California, United States, 95817
      • Site 1070
    • Sherman Oaks, California, United States
      • 1079
    • Sylmar, California, United States, 91342
      • Site 1053
  • Florida
    • DeBary, Florida, United States, 32713
      • Site 1064
    • DeLand, Florida, United States, 32720
      • Site 1052
    • Miami, Florida, United States
      • 1076
  • Indiana
    • Michigan City, Indiana, United States, 46360
      • Site 1051
  • Louisiana
    • Natchitoches, Louisiana, United States, 71457
      • Site 1057
  • Massachusetts
    • New Bedford, Massachusetts, United States, 02740
      • Site 1073
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Site 1055
    • Detroit, Michigan, United States, 48235
      • Site 1062
    • Royal Oak, Michigan, United States, 48073
      • Site 1068
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Site 1058
  • Montana
    • Butte, Montana, United States, 59701
      • Site 1054
  • Ohio
    • Lima, Ohio, United States, 45801
      • Site 1067
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Site 1056
  • Tennessee
    • Hendersonville, Tennessee, United States
      • 1077
  • Texas
    • Houston, Texas, United States, 77070
      • Site 1060
    • Houston, Texas, United States, 77093
      • Site 1069
    • Splendora, Texas, United States, 77372
      • Site 1066
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Site 1059

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Each subject must:

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 (less than or equal to 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 < 4 500 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 of II, III, or IV and be an appropriate candidate for oral antibiotic therapy as treatment for the current episode of CABP.

Exclusion Criteria:

Each subject must NOT:

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., MRSA, 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lefamulin; oral lefamulin, 600mg	Drug: lefamulin; antibacterial agent; Other Names: BC-3781
Active Comparator: Moxifloxacin; oral moxifloxacin, 400mg	Drug: Moxifloxacin; antibacterial agent; Other Names: Avelox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 for the treatment of CABP through the ECR assessment	96 hours +/- 24 hours after first dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	IACR was assessed at the Test-of-Cure Visit; 5 to 10 days after last dose of study drug

Collaborators and Investigators

• Sponsor: Nabriva Therapeutics AG
• Investigators: Study Chair: Leanne Gasink, MD, Nabriva Therapeutics AG

Publications and helpful links

General 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.
• Alexander E, Goldberg L, Das AF, Moran GJ, Sandrock C, Gasink LB, Spera P, Sweeney C, Paukner S, Wicha WW, Gelone SP, Schranz J. Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial. JAMA. 2019 Nov 5;322(17):1661-1671. doi: 10.1001/jama.2019.15468.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: June 20, 2016
• First Submitted That Met QC Criteria: June 22, 2016
• First Posted (Estimate): June 27, 2016

Study Record Updates

• Last Update Posted (Actual): October 23, 2019
• Last Update Submitted That Met QC Criteria: October 22, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Pneumonia; CAP; CABP; Community acquired bacterial pneumonia
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin; Lefamulin
• Other Study ID Numbers: NAB-BC-3781-3102