A Clinical Study to Compare the effectiveness and safety of Lefamulin (BC 3781) Versus Moxifloxacin (With or Without added Linezolid) in Adults With Community-Acquired Bacterial Pneumonia

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2014-005169-63-NL
• Date of registration: 12/10/2015
• Prospective Registration: Yes
• Primary sponsor: Nabriva Therapeutics AG
• Public title: A Clinical Study to Compare the effectiveness and safety of Lefamulin (BC 3781) Versus Moxifloxacin (With or Without added Linezolid) in Adults With Community-Acquired Bacterial Pneumonia
• Scientific 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 - LEAP
• Date of first enrolment: 12/01/2016
• Target sample size: 738
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005169-63
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Bosnia and Herzegovina, Brazil, Bulgaria, Georgia, Hungary, Latvia, Lithuania, Netherlands, Peru, Philippines, Poland, Romania, Russian Federation, Serbia, South Africa, Thailand, Ukraine, United States

Contacts

• Name: Claudia Lell
• Affiliation: Nabriva Therapeutics AG

• Name: Claudia Lell
• Affiliation: Nabriva Therapeutics AG

Key inclusion & exclusion 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 or less 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 24 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.
8. If female, meets the following criteria:
• Surgically sterile or =2 years postmenopausal, or if of childbearing potential (including being <2 years postmenopausal), has a negative pregnancy test, and if participating in sexual activity that may lead to pregnancy, agrees to use an effective dual method of contraception (e.g., condom plus diaphragm, condom plus spermicide, intrauterine device plus spermicide, oral contraceptive plus condom) during the study and for =28 days after the last dose of study drug. If a male partner has been surgically sterile for =1 year, a single contraception method may be used.
• Agrees not to breastfeed during the study and through =28 days after the last dose of study drug.
9. If male, meets the following criteria:
• If not surgically sterile and if participating in sexual activity that may lead to pregnancy, agrees to use an effective dual method of contraception (e.g., condom plus diaphragm, condom plus spermicide, intrauterine device plus spermicide, oral contraceptive plus condom) during the study and through =28 days after the last dose of study drug. If surgically sterile for =1 year, a single contraception method may be used.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 738
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 738

Exclusion criteria:
Each subject must NOT:
1. Have received more than a single dose of a short-acting oral or IV antibacterial for CABP =24 hrs before randomization
• EXCEPTION: Subjects who have received >48 hrs of prior systemic antibacterial therapy for current episode of CABP with unequivocal clinical evidence of treatment failure and isolation of an organism from blood or respiratory tract that is resistant to the prior systemic antibacterial therapy unless the resistance is to fluoroquinolones and, in the case of MRSA, oxazolidinones.
2. Require concomitant systemic antibacterial therapy potentially effective against CABP pathogens.
3. Have been hospitalized for =2 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.
4. Have confirmed or suspected CABP caused by a pathogen known to be resistant to any of the study drugs 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Community-Acquired Bacterial Pneumonia
MedDRA version: 18.1 Level: LLT Classification code 10004051 Term: Bacterial pneumonia, unspecified System Organ Class: 100000004862

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: lefamulin
Product Code: BC -3781
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: lefamulin
CAS Number: 1061337-516
Current Sponsor code: BC-3781
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Trade Name: AVELOX (moxifloxacin) hydrochloride Injection, solution for IV use
Product Name: AVELOX (moxifloxacin) hydrochloride Injection, solution for IV use
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: MOXIFLOXACIN
CAS Number: 186826-86-8
Other descriptive name: AVELOX
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Product Name: lefamulin
Product Code: BC -3781
Pharmaceutical Form: Coated tablet
INN or Proposed INN: lefamulin
CAS Number: 1061337-516
Current Sponsor code: BC-3781
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Trade Name: Avelox 400 mg film-coated tablets
Product Name: Avelox 400 mg film-coated tablets
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: MOXIFLOXACIN
CAS Number: 186826-86-8
Other descriptive name: AVELOX
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Zyvox 600 mg Film-Coated Tablets
Product Name: Zyvox 600 mg Film-Coated Tablets
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: linezolid
CAS Number: 165800-03-3
Other descriptive name: Zyvoxid/Zyvoid/Zyvox
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of

Primary Outcome(s)

Secondary Objective: • Evaluate the Early Clinical Response in the Microbiological Intent to Treat (microITT) Analysis Set.
• Evaluate the Early Clinical Response PLUS improvement in vital signs in the ITT Analysis Set.
• Evaluate the Investigator’s Assessment of Clinical Response at TOC in the microITT and Microbiologically Evaluable at TOC (ME-TOC) Analysis Sets.
• Evaluate the By-Pathogen Microbiologic Response at TOC in the microITT and ME-TOC Analysis Sets.
• Evaluate the safety and tolerability of lefamulin versus comparator in the Safety Analysis Set.
• Evaluate 28 day all-cause mortality in the ITT Analysis Set.

Primary end point(s): • Proportion of Responders for ECR at 96 ± 24 hours following the first dose of study drug in the ITT Analysis Set (FDA)
• Proportion of subjects with an IACR of Success at TOC in the mITT and CE-TOC Analysis Sets (Primary for EMA and secondary for FDA)

Main Objective: • Demonstrate the non-inferiority (NI) of lefamulin versus comparator with respect to the Early Clinical Response (96 ± 24 hours after the first dose of study drug) in the Intent to Treat (ITT) Analysis Set (FDA endpoint).
• Demonstrate the NI of lefamulin versus comparator with respect to the Investigator’s Assessment of Clinical Response at Test of Cure (TOC) (i.e., 5-10 days after the last dose of study drug) in the modified-ITT (mITT) and Clinically Evaluable at TOC (CE-TOC) Analysis Sets (EMA endpoint).

Timepoint(s) of evaluation of this end point: 96 ± 24 hours following the first dose of study drug
5-10 days post last dose - test of cure

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 5-10 days post last dose - test of cure

Secondary end point(s): Efficacy will be assessed by ECR, IACR and by Microbiological Response.

Secondary ID(s)

NAB-BC-3781-3101

Source(s) of Monetary Support

Nabriva Therapeutics AG