Clinical Trials

Date: 2016-04-11

Type of information: Initiation of the trial

phase: 3

Announcement: initiation of the trial

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

Therapeutic area: Infectious diseases

Country: Argentina, Brazil, Bulgaria, Chile, Georgia, Hungary, Republic of Korea, Latvia, Mexico, Peru, Philippines, Poland, Romania, Russian Federation, Serbia, South Africa, Spain, Taiwan, Ukraine, 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. (NCT02813694)

Latest news:

• • On April 11, 2016, Nabriva Therapeutics announced the initiation of the second of two Phase 3 multinational pivotal trials evaluating the safety and efficacy of  lefamulin, for the treatment of adults with community-acquired bacterial pneumonia (CABP). The trial, Lefamulin Evaluation Against Pneumonia (LEAP) 2, will assess the efficacy and safety of oral lefamulin compared with oral moxifloxacin in subjects with moderate CABP. The Phase 3, multinational, randomized, double-blind, placebo-controlled, non-inferiority trial will assess safety and efficacy of oral lefamulin therapy compared to oral moxifloxacin for the treatment of adults with moderate CABP (PORT Risk Class II, III, or IV). The study is designed to enroll approximately 740 patients at approximately 150 centers in the United States, Europe, Asia and selected countries in the southern hemisphere. Patients will be randomized 1:1 to receive either 5 days of active lefamulin (600 mg BID) or 7 days of active moxifloxacin (400 mg QD). At least 50% of patients will have PORT scores III or IV.
• The study is designed to address both the FDA and European Medicines Agency (EMA) regulatory guidelines for the development of antibacterial agents to treat CABP. The FDA primary efficacy endpoint is the early clinical response (ECR). ECR is a programmatically derived endpoint, based on improvement of the patient’s baseline symptoms of CABP at 72 to 120 hours after the first dose of study drug. The EMA primary endpoint is the investigator assessment of clinical success rate (IACR) at test of cure (5-10 days after the last dose of study drug). IACR is based on the investigator’s assessment of a patient’s clinical course. Secondary objectives will evaluate these endpoints in other relevant study populations, microbiologic endpoints to assess pathogen eradication, 28-day mortality, and safety and tolerability.

   

Is general: Yes