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A Study of the Safety and Efficacy of 514G3 in Subjects Hospitalized With Bacteremia Due to Staphylococcus Aureus

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: NCT02357966
Recruitment Status : Completed
First Posted : February 6, 2015
Last Update Posted : February 24, 2017
Sponsor:
Information provided by (Responsible Party):
XBiotech, Inc.

Tracking Information
First Submitted Date  ICMJE January 29, 2015
First Posted Date  ICMJE February 6, 2015
Last Update Posted Date February 24, 2017
Actual Study Start Date  ICMJE May 2015
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 22, 2017)
  • Phase I: Determination of the Maximum Tolerated Dose [ Time Frame: 14 Days ]
    The highest dose administered with no more than one dose limiting toxicity
  • Phase II: Safety and tolerability [ Time Frame: 28 days ]
    The incidence of adverse events, serious adverse events, and laboratory abnormalities will be compared between the 514G3 arm and the placebo arm.
Original Primary Outcome Measures  ICMJE
 (submitted: February 2, 2015)
  • Determination of the Maximum Tolerated Dose [ Time Frame: 14 Days ]
  • Time to sterile culture from date of randomization [ Time Frame: 28 days ]
    The time to sterile culture is the interval in days from the first dose of study drug until 2 consecutive days of negative blood cultures has occurred. The difference in this interval will be compared between patients randomized to placebo and those who received the highest dose of 514G3
Change History Complete list of historical versions of study NCT02357966 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2017)
  • Determination of the serum half-life of 514G3 [ Time Frame: 28 days ]
    Serum levels of 514G3 will be measured at protocol specified timepoints to determine the half-life, and to ensure clearance of the antibody during the follow up period after dosing.
  • Duration of Fever [ Time Frame: 28 days ]
  • Length of hospitalization [ Time Frame: 28 days ]
  • Time to sterile culture from date of randomization [ Time Frame: 28 Days ]
    The time to sterile culture is the interval in days from the first dose of study drug until 2 consecutive days of negative blood cultures has occurred. The difference in this interval will be compared between patients randomized to placebo and those who received the highest dose of 514G3
  • Incidence of Serious Adverse Events [ Time Frame: 28 days ]
    Differences in the incidence of SAEs between the 514G3 and placebo arms will be compared.
  • Opsonophagocytosis Assay [ Time Frame: 14 days ]
    Serum samples from patients will be assessed with an in vitro opsonophagocytosis assay which measures the ability of the serum to mediate uptake of staph aureus by white blood cells. Differences in the levels of activity will be compared between treatment and placebo
Original Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2015)
  • Determination of the serum half-life of 514G3 [ Time Frame: 28 days ]
    Serum levels of 514G3 will be measured at protocol specified timepoints to determine the half-life, and to ensure clearance of the antibody during the follow up period after dosing.
  • Duration of Fever [ Time Frame: 28 days ]
  • Length of hospitalization [ Time Frame: 28 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Safety and Efficacy of 514G3 in Subjects Hospitalized With Bacteremia Due to Staphylococcus Aureus
Official Title  ICMJE A Phase I-II Study of the Safety and Efficacy of a True Human Antibody, 514G3, in Subjects Hospitalized With Bacteremia Due to Staphylococcus Aureus
Brief Summary This study will evaluate the maximum safe dose of the true human monoclonal antibody, 514G3, in the treatment of patients with Staphylococcus Aureus bacteremia. Preliminary evidence of efficacy will be evaluated as well. Patients will receive 514G3 plus antibiotics or placebo plus antibiotics in approximately a 3 to 1 ratio.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Staphylococcus Aureus Bacteremia
Intervention  ICMJE
  • Biological: 514G3
    True Human Monoclonal Antibody
  • Drug: Placebo
    Buffered saline solution
  • Drug: Standard IV antibiotic therapy
    standard antibiotic therapy will be determined by the attending physician and will be guided by the results of cultures with sensitivities.
Study Arms  ICMJE
  • Experimental: 514G3
    Phase I of the study will include a single dose of 514G3 at three different dose levels. Phase II utilizes a single dose of 514G3 at the highest dose level. Standard antibiotic therapies will be used in both phases.
    Interventions:
    • Biological: 514G3
    • Drug: Standard IV antibiotic therapy
  • Placebo Comparator: Placebo
    Both Phase I and II will include a single dose of placebo in addition to standard antibiotic therapies.
    Interventions:
    • Drug: Placebo
    • Drug: Standard IV antibiotic therapy
Publications * Not Provided

*   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: February 2, 2015)
52
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2017
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. One or more blood cultures positive for staphylococcus aureus within 2 days of initiating treatment with 514G3.
  2. Temperature ≥ 38.0°C
  3. Age ≥18, male or female subjects.
  4. Adequate renal function, defined by serum creatinine ≤ 2 times the upper limit of normal (ULN).
  5. Adequate hepatic function
  6. Adequate bone marrow function
  7. For women of childbearing potential (WOCBP), a negative serum pregnancy test result at Screening.
  8. Signed and dated institutional review board (IRB)/ Ethics Committee (EC)-approved informed consent before any protocol-specific screening procedures are performed.
  9. Expected survival of at least 2 months.

Exclusion Criteria:

  1. Polymicrobial bacteremia.
  2. Known or suspected osteomyelitis or meningitis.
  3. Patients that are being mechanically ventilated as a result of a pulmonary infection at the time of screening. Mechanical ventilation for other reasons, such as trauma, is acceptable.
  4. Presence of any removable infection source (e.g., intravascular line, abscess, or prosthesis) that will not be removed or debrided within 3 days after randomization.
  5. Definite or possible left-sided endocarditis, by Modified Duke Criteria, based on screening echocardiogram. Subjects with suspected right-sided endocarditis are permitted.
  6. Need for emergent valve surgery at the time of screening, and/or the presence of decompensated heart failure or cardiogenic shock.
  7. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
  8. Infection with human immunodeficiency virus (HIV) and a CD4 count <200 cells/mm3.
  9. Subjects with history of hypersensitivity to compounds of similar chemical or biologic composition to 514G3 or any component of its formulations.
  10. Women who are pregnant or breastfeeding.
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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02357966
Other Study ID Numbers  ICMJE 2014-PT029
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party XBiotech, Inc.
Study Sponsor  ICMJE XBiotech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Mark Rupp, M.D. University of Nebraska
PRS Account XBiotech, Inc.
Verification Date February 2017

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