Clinical trial NCT02559310: Study to Compare Lefamulin to Moxifloxacin (With or Without Linezolid) for the Treatment of Adults With Pneumonia
Official title: A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Lefamulin (BC 3781) Versus Moxifloxacin (With or Without Adjunctive Linezolid) in Adults With Community-Acquired Bacterial Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Community Acquired Pneumonia
Keywords: Pneumonia
CABP
CAP
Community acquired bacterial pneumonia
Lead sponsor: Nabriva Therapeutics AG
Sponsor class: INDUSTRY
First posted: 2015-09-24
Enrollment: 551
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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:

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.

Primary outcomes:
measure: Early Clinical Response (ECR)
timeFrame: ECR was assessed 96 +/- 24 hours after the first dose of study drug.
Secondary outcomes:
measure: Investigator's Assessment of Clinical Response (IACR)
timeFrame: IACR was assessed at the Test-of-Cure visit; 5-10 days after the last dose of study drug.
measure: Investigator's Assessment of Clinical Response (IACR)
timeFrame: IACR was assessed at the Test of Cure visit, 5 - 10 days after the last dose of study drug.
Other outcomes:
Locations:
city: Hazard
country: United States
facility: Site 1006
state: Kentucky
city: Shreveport
country: United States
facility: Site 1008
state: Louisiana
city: Minneapolis
country: United States
facility: Site 1005
state: Minnesota
city: Butte
country: United States
facility: Site 1001
state: Montana
city: Akron
country: United States
facility: Site 1009
state: Ohio
city: Dayton
country: United States
facility: Site 1002
state: Ohio
city: Splendora
country: United States
facility: Site 1004
state: Texas
city: La Plata
country: Argentina
facility: Site 3005
state: Buenos Aires
city: Rosario
country: Argentina
facility: Site 3006
state: Santa Fe
city: Cordoba
country: Argentina
facility: Site 3004
city: Córdoba
country: Argentina
facility: Site 3003
city: Córdoba
country: Argentina
facility: Site 3007
city: Córdoba
country: Argentina
facility: Site 3001
city: Mostar
country: Bosnia and Herzegovina
facility: Site 4003
city: Tuzla
country: Bosnia and Herzegovina
facility: Site 4001
city: Zenica
country: Bosnia and Herzegovina
facility: Site 4004
city: Belo Horizonte
country: Brazil
facility: Site 3104
state: Minas Gerais
city: Passo Fundo
country: Brazil
facility: Site 3102
state: Rio Grande Do Sol
city: Campinas
country: Brazil
facility: Site 3103
state: Sao Paulo
city: Sao Paulo Do Rio Preto
country: Brazil
facility: Site 3101
state: Sao Paulo
city: Gabrovo
country: Bulgaria
facility: Site 4105
city: Lovech
country: Bulgaria
facility: Site 4107
city: Pernik
country: Bulgaria
facility: Site 4112
city: Ruse
country: Bulgaria
facility: Site 4103
city: Smolyan
country: Bulgaria
facility: Site 4108
city: Sofia
country: Bulgaria
facility: Site 4102
city: Sofia
country: Bulgaria
facility: Site 4101
city: Sofia
country: Bulgaria
facility: Site 4106
city: Sofia
country: Bulgaria
facility: Site 4110
city: Sofia
country: Bulgaria
facility: Site 4111
city: Veliko Tarnovo
country: Bulgaria
facility: Site 4104
city: Vidin
country: Bulgaria
facility: Site 4109
city: Tbilisi
country: Georgia
facility: Site 4206
city: Tbilisi
country: Georgia
facility: Site 4204
city: Tbilisi
country: Georgia
facility: Site 4205
city: Tbilisi
country: Georgia
facility: Site 4201
city: Tbilisi
country: Georgia
facility: Site 4202
city: Budapest
country: Hungary
facility: Site 4305
city: Csorna
country: Hungary
facility: Site 4306
city: Debrecen
country: Hungary
facility: Site 4304
city: Farkasgyepű
country: Hungary
facility: Site 4302
city: Miskolc
country: Hungary
facility: Site 4307
city: Miskolc
country: Hungary
facility: Site 4308
city: Törökbálint
country: Hungary
facility: Site 4303
city: Daugavpils
country: Latvia
facility: Site 4403
city: Liepaja
country: Latvia
facility: Site 4401
city: Riga
country: Latvia
facility: Site 4402
city: Almelo
country: Netherlands
facility: Site 4603
state: Overijssel
city: Helmond
country: Netherlands
facility: Site 4602
city: Trujillo
country: Peru
facility: Site 3205
state: La Libertad
city: Lima
country: Peru
facility: Site 3202
city: Lima
country: Peru
facility: Site 3204
city: Lima
country: Peru
facility: Site 3201
city: Iloilo City
country: Philippines
facility: Site 2005
city: Manila City
country: Philippines
facility: Site 2003
city: Manila
country: Philippines
facility: Site 2004
city: Quezon City
country: Philippines
facility: Site 2002
city: Quezon City
country: Philippines
facility: Site 2001
city: Skierniewice
country: Poland
facility: Site 4703
state: Lódzkie
city: Warszawa
country: Poland
facility: Site 4704
state: Mazowieckie
city: Lódz
country: Poland
facility: Site 4701
city: Wilkowice
country: Poland
facility: Site 4702
city: Palazu Mare
country: Romania
facility: Site 4802
state: Constanta
city: Bucharest
country: Romania
facility: Site 4801
city: Bucharest
country: Romania
facility: Site 4806
city: Bucuresti
country: Romania
facility: Site 4810
city: Cluj-Napoca
country: Romania
facility: Site 4811
city: Craiova
country: Romania
facility: Site 4803
city: Craiova
country: Romania
facility: Site 4808
city: Timisoara
country: Romania
facility: Site 4807
city: Timisoara
country: Romania
facility: Site 4809
city: Chelyabinsk
country: Russian Federation
facility: Site 4904
city: Novosibirsk
country: Russian Federation
facility: Site 4902
city: Smolensk
country: Russian Federation
facility: Site 4906
city: St. Petersburg
country: Russian Federation
facility: Site 4903
city: St. Petersburg
country: Russian Federation
facility: Site 4901
city: Yaroslavl
country: Russian Federation
facility: Site 4905
city: Nis
country: Serbia
facility: Site 5003
state: Nišavski Okrug
city: Belgrade
country: Serbia
facility: Site 5002
city: Sremska Kamenica
country: Serbia
facility: Site 5004
city: Kragujevac
country: Serbia
facility: Site 5001
state: Šumadijski Okrug
city: Benoni
country: South Africa
facility: Site 5103
state: Gauteng
city: Pretoria
country: South Africa
facility: Site 5104
state: Gauteng
city: Thabazimbi
country: South Africa
facility: Site 5105
state: Limpopo
city: Middelburg
country: South Africa
facility: Site 5101
state: Mpumalanga
city: Krugersdorp
country: South Africa
facility: Site 5102
city: Nonthaburi
country: Thailand
facility: Site 2103
city: Chernivtsi
country: Ukraine
facility: Site 5203
state: Chernivets'ka Oblast
city: Ivano-Frankivsk
country: Ukraine
facility: Site 5204
state: Ivano-Frankivs'ka Oblast
city: Kharkiv
country: Ukraine
facility: Site 5201
state: Kharkivs'ka Oblast
city: Kherson
country: Ukraine
facility: Site 5209
state: Khersons'ka Oblast
city: Odesa
country: Ukraine
facility: Site 5211
state: Odes'ka Oblast
city: Zaporizhzhia
country: Ukraine
facility: Site 5210
state: Zaporiz'ka Oblast
city: Kyiv
country: Ukraine
facility: Site 5202
city: Kyiv
country: Ukraine
facility: Site 5205
city: Kyïv
country: Ukraine
facility: Site 5207
city: Sumy
country: Ukraine
facility: Site 5208
city: Zaporizhzhia
country: Ukraine
facility: Site 5212
city: Zhytomyr
country: Ukraine
facility: Site 5206
Study officials:
affiliation: Nabriva Therapeutics
name: Jennifer Schranz, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.