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Study to Compare Lefamulin to Moxifloxacin for the Treatment of Adults With Pneumonia (LEAP2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02813694
Recruitment Status : Completed
First Posted : June 27, 2016
Results First Posted : October 23, 2019
Last Update Posted : October 23, 2019
Sponsor:
Information provided by (Responsible Party):
Nabriva Therapeutics AG

Tracking Information
First Submitted Date  ICMJE June 20, 2016
First Posted Date  ICMJE June 27, 2016
Results First Submitted Date  ICMJE August 28, 2019
Results First Posted Date  ICMJE October 23, 2019
Last Update Posted Date October 23, 2019
Actual Study Start Date  ICMJE August 2016
Actual Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 22, 2019)
Early Clinical Response (ECR) [ Time Frame: 96 hours +/- 24 hours after first dose of study drug ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: June 22, 2016)
Early Clinical Response: proportion of patients with improvement in symptoms over time [ Time Frame: 96 hours after first dose of study drug ]
Assessment of clinical symptoms of pneumonia
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 22, 2019)
Investigator's Assessment of Clinical Response (IACR) [ Time Frame: IACR was assessed at the Test-of-Cure Visit; 5 to 10 days after last dose of study drug ]
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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2016)
  • Early Clinical Response in the microbiological intent-to-treat population: proportion of patients with improvement in symptoms over time [ Time Frame: 96 hours after the first dose of study drug ]
    Assessment of clinical symptoms of pneumonia
  • Investigator's Assessment of Clinical Response in the modified intent-to-treat and clinically evaluable populations: proportion of patients deemed success based upon improvement in baseline signs and symptoms of disease [ Time Frame: 5 to 10 days after last dose of study drug ]
    Assessment of clinical response
  • Safety and tolerability: assessment of adverse events, laboratory parameters and vital signs [ Time Frame: From screening to 30 days post first dose ]
    Evaluation of adverse event throughout the study
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Compare Lefamulin to Moxifloxacin for the Treatment of Adults With Pneumonia
Official Title  ICMJE 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
Brief Summary This study evaluates the safety and efficacy of lefamulin, a pleuromutilin, for the treatment of adults with moderate community-acquired bacterial pneumonia
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Community Acquired Pneumonia
Intervention  ICMJE
  • Drug: lefamulin
    antibacterial agent
    Other Name: BC-3781
  • Drug: Moxifloxacin
    antibacterial agent
    Other Name: Avelox
Study Arms  ICMJE
  • Experimental: lefamulin
    oral lefamulin, 600mg
    Intervention: Drug: lefamulin
  • Active Comparator: Moxifloxacin
    oral moxifloxacin, 400mg
    Intervention: Drug: Moxifloxacin
Publications * Alexander E, Goldberg L, Das AF, Moran GJ, Sandrock C, Gasink LB, Spera P, Sweeney C, Paukner S, Wicha WW, Gelone SP, Schranz J. Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial. JAMA. 2019 Sep 27. doi: 10.1001/jama.2019.15468. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 22, 2016)
738
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2018
Actual Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Bulgaria,   Chile,   Georgia,   Hungary,   Korea, Republic of,   Latvia,   Mexico,   Peru,   Philippines,   Poland,   Romania,   Russian Federation,   Serbia,   South Africa,   Spain,   Taiwan,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02813694
Other Study ID Numbers  ICMJE NAB-BC-3781-3102
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nabriva Therapeutics AG
Study Sponsor  ICMJE Nabriva Therapeutics AG
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Leanne Gasink, MD Nabriva Therapeutics AG
PRS Account Nabriva Therapeutics AG
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP