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

Community Acquired Pneumonia Clinical Trial

— LEAP2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02813694
• Other study ID #: NAB-BC-3781-3102
• Status: Completed
• Phase: Phase 3
• Start date: August 2016
• Est. completion date: January 2018

Study information

• Verified date: September 2019
• Source: Nabriva Therapeutics AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 738
• Est. completion date: January 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Community Acquired Pneumonia
• Pneumonia

Intervention

Drug:
• lefamulin
antibacterial agent
• Moxifloxacin
antibacterial agent

Locations

Country	Name	City	State
Argentina	Site 3059	Buenos Aires AV
Argentina	Site 3056	Ciudad Autónoma de Buenos Aires
Argentina	Site 3052	Cordoba
Argentina	Site 3054	Cordoba
Argentina	Site 3057	Cordoba
Argentina	Site 3058	General Pacheco
Argentina	Site 3051	La Plata
Argentina	Site 3053	La Plata
Brazil	Site 3154	Belo Horizonte
Brazil	Site 3153	Passo Fundo
Brazil	Site 3152	Sao Jose do Rio Preto
Bulgaria	4162	Ruse
Bulgaria	Site 4154	Sliven
Bulgaria	4163	Sofia
Bulgaria	4164	Sofia
Bulgaria	4165	Sofia
Bulgaria	Site 4153	Sofia
Bulgaria	Site 4156	Sofia
Bulgaria	Site 4157	Sofia
Bulgaria	Site 4160	Sofia
Bulgaria	Site 4161	Sofia
Bulgaria	Site 4158	Stara Zagora
Bulgaria	Site 4159	Vidin
Bulgaria	Site 4152	Vratsa
Chile	Site 3353	Santiago
Chile	Site 3356	Santiago
Chile	Site 3357	Santiago
Chile	Site 3354	Talca
Chile	Site 3352	Temuco
Chile	Site 3355	Valdivia
Georgia	Site 4256	Batumi
Georgia	Site 4252	Tbilisi
Georgia	Site 4253	Tbilisi
Georgia	Site 4254	Tbilisi
Georgia	Site 4255	Tbilisi
Hungary	Site 4353	Budapest
Hungary	Site 4354	Budapest
Hungary	Site 4352	Matrahaza
Hungary	Site 4351	Torokbalint
Korea, Republic of	Site 2257	Bucheon-si
Korea, Republic of	Site 2253	Daegu
Korea, Republic of	Site 2251	Seoul
Korea, Republic of	Site 2252	Seoul
Korea, Republic of	Site 2255	Seoul
Korea, Republic of	Site 2256	Seoul
Korea, Republic of	Site 2254	Uijeongbu Si	Gyeonggi-do
Latvia	Site 4451	Liepaja
Latvia	Site 4453	Riga
Latvia	Site 4452	Valmiera
Mexico	Site 1153	Aguascalientes
Mexico	Site 1154	Guadalajara
Mexico	Site 1151	Monterrey
Mexico	Site 1152	Toluca
Peru	Site 3262	Arequipa
Peru	Site 3263	Cusco
Peru	Site 3261	Cuzco
Peru	Site 3264	Grau	Lima
Peru	Site 3254	Ica
Peru	Site 3259	Iquitos
Peru	Site 3251	La Libertad
Peru	Site 3252	Lima
Peru	Site 3253	Lima
Peru	Site 3255	Lima
Peru	Site 3257	Lima
Peru	Site 3260	Lima
Peru	Site 3265	Lima
Peru	Site 3258	Lima Lima
Peru	Site 3256	Piura
Philippines	Site 2053	Caloocan City
Philippines	Site 2055	Cebu
Philippines	Site 2052	Iloilo City
Philippines	Site 2054	Quezon
Philippines	Site 2051	Quezon City
Philippines	Site 2056	Quezon City
Poland	Site 4755	Bochnia
Poland	Site 4754	Chodziez
Poland	Site 4753	Krakow
Poland	Site 4756	Kraków
Poland	Site 4757	Siedlce
Romania	Site 4854	Bucuresti
Romania	Site 4855	Bucuresti
Romania	Site 4858	Bucuresti
Romania	Site 4853	Cluj-Napoca
Romania	Site 4851	Codlea
Romania	Site 4857	Craiova
Romania	Site 4856	Timisoara
Russian Federation	Site 4953	Barnaul
Russian Federation	Site 4952	Moscow
Russian Federation	Site 4957	Moscow
Russian Federation	Site 4954	Novosibirsk
Russian Federation	Site 4959	Saratov
Russian Federation	Site 4958	Smolensk
Russian Federation	Site 4951	St. Petersburg
Russian Federation	Site 4955	St. Petersburg
Serbia	5057	Belgrade
Serbia	Site 5051	Belgrade
Serbia	Site 5052	Belgrade
Serbia	Site 5056	Belgrade
Serbia	Site 5055	Knez Selo
Serbia	Site 5054	Kragujevac
Serbia	Site 5053	Sremska Kamenica
South Africa	Site 5151	Bloemfontein
South Africa	Site 5154	Krugersdorp
South Africa	Site 5155	Middelburg
South Africa	Site 5156	Pretoria
South Africa	Site 5152	Queenswood
South Africa	Site 5153	Witbank
Spain	Site 4554	Alicante
Spain	Site 4556	Badalona
Spain	Site 4552	Barcelona
Spain	Site 4555	Barcelona
Spain	Site 4551	Madrid
Spain	Site 4553	Madrid
Taiwan	Site 2351	Kaohsiung
Taiwan	Site 2352	Kaohsiung
Taiwan	Site 2354	Taipei
Ukraine	Site 5264	Chernivtsi
Ukraine	Site 5258	Ivano-Frankivs'k
Ukraine	Site 5261	Ivano-Frankivs'k
Ukraine	Site 5254	Kharkiv
Ukraine	Site 5256	Kharkiv
Ukraine	Site 5255	Kherson
Ukraine	Site 5251	Kyiv
Ukraine	SIte 5252	Kyiv
Ukraine	Site 5263	Kyiv
Ukraine	Site 5265	Kyiv
Ukraine	Site 5259	Poltava
Ukraine	Site 5260	Vinnytsya
Ukraine	Site 5253	Zaporizhzhya
Ukraine	Site 5257	Zaporizhzhya
United States	1080	Beverly Hills	California
United States	Site 1054	Butte	Montana
United States	Site 1059	Charlottesville	Virginia
United States	Site 1064	DeBary	Florida
United States	Site 1052	DeLand	Florida
United States	Site 1055	Detroit	Michigan
United States	Site 1062	Detroit	Michigan
United States	Site 1065	Fresno	California
United States	1077	Hendersonville	Tennessee
United States	Site 1060	Houston	Texas
United States	Site 1069	Houston	Texas
United States	Site 1067	Lima	Ohio
United States	1076	Miami	Florida
United States	Site 1051	Michigan City	Indiana
United States	Site 1057	Natchitoches	Louisiana
United States	Site 1073	New Bedford	Massachusetts
United States	1078	Northridge	California
United States	Site 1072	Oxnard	California
United States	Site 1056	Rapid City	South Dakota
United States	Site 1068	Royal Oak	Michigan
United States	Site 1070	Sacramento	California
United States	Site 1058	Saint Louis	Missouri
United States	1079	Sherman Oaks	California
United States	Site 1066	Splendora	Texas
United States	Site 1053	Sylmar	California

Sponsors (1)

Lead Sponsor	Collaborator
Nabriva Therapeutics AG

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Chile,  Georgia,  Hungary,  Korea, Republic of,  Latvia,  Mexico,  Peru,  Philippines,  Poland,  Romania,  Russian Federation,  Serbia,  South Africa,  Spain,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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