Clinical Trial: Study to Assess the Effects of Intravenous Bendavia in Patients Undergoing Percutaneous Transluminal Angioplasty of the Renal Artery (PTRA)

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase 2a, Randomized, Placebo-controlled, Single Center Trial to Evaluate the Impact of Intravenous Bendavia™ (MTP-131) on Ischemia Reperfusion Injury in Atherosclerotic Renal Artery Stenosis

Brief Summary: The primary objective of this trial is to assess the effects of Bendavia on renal blood flow and renal function in atherosclerotic renal artery stenosis (ARAS), compared with placebo in patients with ARAS who receive one dose of study drug infused 30 minutes before and 3 hours after percutaneous transluminal angioplasty of the renal artery (PTRA).

Detailed Summary:
Sponsor: Stealth BioTherapeutics Inc.

Current Primary Outcome: Comparison between treatment groups in the change in the glomerular filtration rate (GFR), as measured by iothalamate clearance, from before percutaneous renal artery angioplasty (PTRA) to 8 weeks post-PTRA. [ Time Frame: Baseline (prior to PTRA) to 8 weeks post-PTRA ]

Comparison between treatment groups of the measurement of GFR calculated from measurements from the clinical chemistry laboratory obtained during iothalamate clearance testing the day prior to PTRA and 8 weeks post-PTRA.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mean change in renal volume (ml) as measured using Multi-Detector Computed Tomography (MDCT) from pre-PTRA to 8 weeks post-PTRA with and without Bendavia. [ Time Frame: Pre-PTRA and 8 weeks post-PTRA ]
    MDCT will be performed at pre-PTRA and 8 weeks post-PTRA for assessment of renal volume. Change in renal volume from baseline to post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in renal volume for each subject by cohort.
  • Mean change in regional perfusion (medulla) (ml/minute/ml of tissue) as measured using Multi-Detector Computed Tomography (MDCT) from pre-PTRA to 8 weeks post-PTRA with and without Bendavia. [ Time Frame: Pre-PTRA to 8 weeks post-PTRA ]
    MDCT will be performed at pre-PTRA and 8 weeks post-PTRA for assessment of regional perfusion (medulla). Change in regional perfusion (medulla) from baseline to post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in regional perfusion (medulla)for each subject by cohort.
  • Mean change in regional perfusion (cortex) (ml/minute/ml of tissue) as measured using Multi-Detector Computed Tomography (MDCT) from pre-PTRA to 8 weeks post-PTRA with and without Bendavia. [ Time Frame: Pre-PTRA to 8 weeks post-PTRA ]
    MDCT will be performed at pre-PTRA and 8 weeks post-PTRA for assessment of regional perfusion (cortex). Change in regional perfusion (cortex) from baseline to post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in regional perfuson (cortex) for each subject by cohort.
  • Mean change in glomerular flow rate (ml/minute) as measured using Multi-Detector Computed Tomography (MDCT) from pre-PTRA to 8 weeks post-PTRA with and without Bendavia. [ Time Frame: Pre-PTRA to 8 weeks post-PTRA ]
    MDCT will be performed at pre-PTRA and 8 weeks post-PTRA for assessment of glomerular flow rate. Change in glomerular flow rate from baseline to post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in glomerular flow rate for each subject by cohort.
  • Mean change in renal blood flow (ml/minute) as measured using Multi-Detector Computed Tomography (MDCT) from pre-PTRA to 8 weeks post-PTRA with and without Bendavia. [ Time Frame: Pre-PTRA to 8 weeks post-PTRA ]
    MDCT will be performed at pre-PTRA and 8 weeks post-PTRA for assessment of renal blood flow. Change in renal blood flow from baseline to post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in renal blood flow for each subject by cohort.
  • Mean change in renal oxygenation between pre-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA as measured by calculation of fractional hypoxia using blood oxygenation level-dependent magnetic resonance (BOLD-MR) imaging, with and without Bendavia. [ Time Frame: Pre-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA ]
    BOLD-MR will be performed at pre-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA for assessment of fractional hypoxia. Change in fractional hypoxia from baseline to both 27 hours and 8 week post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in fractional hypoxia for each subject at each time point by cohort.
  • Mean change in plasma 8-isoprostane (8-iso prostaglandin F2-alpha) levels (pg/ml) from pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA, with and without Bendavia. [ Time Frame: Pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA ]
    Assay of plasma for 8-isoprostane levels will be performed on samples at pre-PTRA, immediately post-PTRA and 8 weeks post-PTRA. Change in 8-isoprostane levels from baseline to both immediately and 8 week post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in 8-isoprostane for each subject at each time point by cohort.
  • Mean change in Monocyte Chemotactic Protein-1 (MCP-1) levels (pg/ml) from pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA, with and without Bendavia. [ Time Frame: Pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA ]
    Assay of plasma for MCP-1 levels will be performed on samples at pre-PTRA, immediately post-PTRA and 8 weeks post-PTRA. Change in MCP-1 levels from baseline to both immediately and 8 week post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in MCP-1 for each subject at each time point by cohort.
  • Mean change in Tumor Necrosis Factor-alpha (TNF-a) levels (pg/ml) from pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA, with and without Bendavia. [ Time Frame: Pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA ]
    Assay of plasma for TNF-a levels will be performed on samples at pre-PTRA, immediately post-PTRA and 8 weeks post-PTRA. Change in TNF-a levels from baseline to both immediately and 8 week post-PTRA will be calculated for each subject. M

    Original Secondary Outcome:

    • Mean change in renal volume (ml) as measured using Multi-Detector Computed Tomography (MDCT) from pre-PTRA to 8 weeks post-PTRA with and without Bendavia. [ Time Frame: Pre-PTRA and 8 weeks post-PTRA ]
      MDCT will be performed at pre-PTRA and 8 weeks post-PTRA for assessment of renal volume. Change in renal volume from baseline to post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in renal volume for each subject by cohort.
    • Mean change in regional perfusion (medulla) (ml/minute/ml of tissue) as measured using Multi-Detector Computed Tomography (MDCT) from pre-PTRA to 8 weeks post-PTRA with and without Bendavia. [ Time Frame: Pre-PTRA to 8 weeks post-PTRA ]
      MDCT will be performed at pre-PTRA and 8 weeks post-PTRA for assessment of regional perfusion (medulla). Change in regional perfusion (medulla) from baseline to post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in regional perfusion (medulla)for each subject by cohort.
    • Mean change in regional perfusion (cortex) (ml/minute/ml of tissue) as measured using Multi-Detector Computed Tomography (MDCT) from pre-PTRA to 8 weeks post-PTRA with and without Bendavia. [ Time Frame: Pre-PTRA to 8 weeks post-PTRA ]
      MDCT will be performed at pre-PTRA and 8 weeks post-PTRA for assessment of regional perfusion (cortex). Change in regional perfusion (cortex) from baseline to post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in regional perfuson (cortex) for each subject by cohort.
    • Mean change in glomerular flow rate (ml/minute) as measured using Multi-Detector Computed Tomography (MDCT) from pre-PTRA to 8 weeks post-PTRA with and without Bendavia. [ Time Frame: Pre-PTRA to 8 weeks post-PTRA ]
      MDCT will be performed at pre-PTRA and 8 weeks post-PTRA for assessment of glomerular flow rate. Change in glomerular flow rate from baseline to post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in glomerular flow rate for each subject by cohort.
    • Mean change in renal blood flow (ml/minute) as measured using Multi-Detector Computed Tomography (MDCT) from pre-PTRA to 8 weeks post-PTRA with and without Bendavia. [ Time Frame: Pre-PTRA to 8 weeks post-PTRA ]
      MDCT will be performed at pre-PTRA and 8 weeks post-PTRA for assessment of renal blood flow. Change in renal blood flow from baseline to post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in renal blood flow for each subject by cohort.
    • Mean change in renal oxygenation between pre-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA as measured by calculation of fractional hypoxia using blood oxygenation level-dependent magnetic resonance (BOLD-MR) imaging, with and without Bendavia. [ Time Frame: Pre-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA ]
      BOLD-MR will be performed at pre-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA for assessment of fractional hypoxia. Change in fractional hypoxia from baseline to both 27 hours and 8 week post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in fractional hypoxia for each subject at each time point by cohort.
    • Mean change in plasma 8-isoprostane (8-iso prostaglandin F2-alpha) levels (pg/ml) from pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA, with and without Bendavia. [ Time Frame: Pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA ]
      Assay of plasma for 8-isoprostane levels will be performed on samples at pre-PTRA, immediately post-PTRA and 8 weeks post-PTRA. Change in 8-isoprostane levels from baseline to both immediately and 8 week post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in 8-isoprostane for each subject at each time point by cohort.
    • Mean change in Monocyte Chemotactic Protein-1 (MCP-1) levels (pg/ml) from pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA, with and without Bendavia. [ Time Frame: Pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA ]
      Assay of plasma for MCP-1 levels will be performed on samples at pre-PTRA, immediately post-PTRA and 8 weeks post-PTRA. Change in MCP-1 levels from baseline to both immediately and 8 week post-PTRA will be calculated for each subject. Mean change from baseline is defined as the mean of the change in MCP-1 for each subject at each time point by cohort.
    • Mean change in Tumor Necrosis Factor-alpha (TNF-a) levels (pg/ml) from pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA, with and without Bendavia. [ Time Frame: Pre-PTRA and then immediately post-PTRA and 8 weeks post-PTRA ]
      Assay of plasma for TNF-a levels will be performed on samples at pre-PTRA, immediately post-PTRA and 8 weeks post-PTRA. Change in TNF-a levels from baseline to both immediately and 8 week post-PTRA will be calculated for each subject. M

      Information By: Stealth BioTherapeutics Inc.

      Dates:
      Date Received: December 19, 2012
      Date Started: December 2012
      Date Completion:
      Last Updated: June 3, 2016
      Last Verified: June 2016