Clinical Trials

Date: 2017-04-11

Type of information: Completion of patient enrollment

phase: 3

Announcement: completion of patient enrollment

Company: Nabriva Therapeutics (Austria)

Product: lefamulin (BC 3781)

Action mechanism: antibioctic/pleuromulin derivative. Lefamulin (BC 3781) belongs to the first generation of pleuromutilins to combine excellent systemic bioavailability with substantial activity against Gram-positive pathogens, and fastidious Gram-negative pathogens plus atypical pathogens. Pleuromutilins interfere with bacterial protein synthesis via a specific interaction with the 23S rRNA of the 50S bacterial ribosome subunit. These antibacterials have a distinct anti-bacterial profile. Their unique mechanism of action implies a very low probability of cross resistance with other antibacterials. In an industry first, Nabriva\'s world class medicinal chemistry expertise achieved the development of intravenous and orally available pleuromutilins clearing the way for i.v. and oral therapy with this antibiotic class. This achievement constitutes a significant milestone in providing appropriate medication for the treatment of life-threatening bacterial infections offering a distinctly different class of antibiotics for the treatment of bacterial diseases. Lefamulin is highly active against multi-drug resistant (MDR) pathogens including Methicillin resistant Staphylococcus aureus (MRSA), MDR Streptococcus pneumoniae, Vancomycin resistant Enterococcus faecium.

Disease: community-acquired bacterial pneumonia (CABP)

Therapeutic area: Infectious diseases

Country: USA

Trial details: The LEAP program is comprised of two global, registrational Phase 3 clinical trials evaluating lefamulin for the treatment of CABP. LEAP 1 is a multi-center, randomized, controlled, double-blind trial comparing the safety and efficacy of lefamulin (IV/po) to moxifloxacin (IV/po) in moderate to severe CABP patients. If an investigator suspects MRSA at randomization, linezolid will be added to moxifloxacin, while matching placebo will be added to lefamulin. After three days of IV trial medication, investigators have the option to switch patients to oral therapy based on pre-defined criteria to complete treatment (a total of 7 days of therapy; for confirmed MRSA, a total of 10 days of therapy). The company is targeting the randomization of approximately 550 patients in this trial. LEAP 2 is a multi-center, randomized, controlled, double-blind trial comparing the safety and efficacy of 5 days of oral lefamulin to 7 days of oral moxifloxacin in patients with moderate CABP. The company is targeting the randomization of approximately 738 patients in this trial. (NCT02559310)

Latest news:

• • On April 11, 2017, Nabriva Therapeutics announced that it has completed enrollment in its first lefamulin evaluation against pneumonia (LEAP 1) Phase 3 clinical trial. LEAP 1, which is designed to assess the efficacy and safety of lefamulin (IV/oral) compared to moxifloxacin (IV/oral) in patients with moderate to severe community-acquired bacterial pneumonia (CABP), met its enrollment target of 550 patients. The company anticipates availability of top-line clinical data from LEAP 1 in the third quarter of 2017. Nabriva will continue to enroll its second pivotal Phase 3 clinical trial, LEAP 2, which is evaluating efficacy and safety of oral lefamulin for the treatment of patients with moderate CABP. Based on current projections, patient enrollment for LEAP 2 could be completed in the fourth quarter of 2017 and top-line data are anticipated in the first quarter of 2018.
• • On February 2, 2017, Nabriva Therapeutics announced that following a blinded interim analysis, an independent committee recommended no sample size adjustment for the lefamulin evaluation against pneumonia (LEAP) 1 Phase 3 clinical trial. This was a prospectively defined, blinded interim analysis to confirm the sample size and power assumptions that was planned to occur after the trial achieved 60% of its enrollment target. The company expects to complete LEAP 1 enrollment of approximately 550 patients with moderate to severe community-acquired bacterial pneumonia (CABP) in the second quarter of 2017 and announce topline LEAP 1 data by the end of the third quarter of 2017.

 

•   • On December 20, 2016, Nabriva Therapeutics announced that it has achieved 60% of its enrollment target in the lefamulin evaluation against pneumonia (LEAP) 1 trial. Based on current sample size estimates, the company expects to complete enrollment of 550 patients by the end of the second quarter of 2017.
• • On October 13, 2015, Nabriva Therapeutics announced that the company expects to begin enrolling patients in the first of two Phase 3 clinical studies of lefamulin for the treatment of community acquired bacterial pneumonia (CABP) in the fourth quarter of 2015.

Is general: Yes