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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Stealth Peptides Inc.
Sponsor:
Information provided by (Responsible Party):
Stealth Peptides Inc.
ClinicalTrials.gov Identifier:
NCT01755858
First received: December 19, 2012
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

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).


Condition Intervention Phase
Renal Artery Obstruction
Hypertension, Renovascular
Ischemia Reperfusion Injury
Drug: Bendavia
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
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 in Patients Undergoing Percutaneous Transluminal Angioplasty of the Renal Artery (PTRA)

Resource links provided by NLM:


Further study details as provided by Stealth Peptides Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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. Mean change from baseline is defined as the mean of the change in TNF-a for each subject at each time point by cohort.

  • Mean change in Interferon-Gamma (IFN-gamma) 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 ] [ Designated as safety issue: No ]
    Assay of plasma for IFN-gamma levels will be performed on samples at pre-PTRA, immediately post-PTRA and 8 weeks post-PTRA. Change in IFN-gamma 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 IFN-gamma for each subject at each time point by cohort.

  • Mean change in Interleukin-10 (IL-10) 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 ] [ Designated as safety issue: No ]
    Assay of plasma for IL-10 levels will be performed on samples at pre-PTRA, immediately post-PTRA and 8 weeks post-PTRA. Change in IL-10 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 IL-10 for each subject at each time point by cohort.

  • Mean change in Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels (pg/ml) from pre-PTRA to immediately post-PTRA, 3, 9, 15, 21, and 27 hours post-PTRA and then 8 weeks post-PTRA, with and without Bendavia. [ Time Frame: Pre-PTRA to immediately post-PTRA, 3, 9, 15, 21, and 27 hours post-PTRA and then 8 weeks post-PTRA ] [ Designated as safety issue: No ]
    Assay of plasma for NGAL levels will be performed on samples at pre-PTRA, immediately post-PTRA, 3, 9, 15, 21 and 27 hours post-PTRA and 8 weeks post-PTRA. Change in NGAL levels from baseline to all post-PTRA time points will be calculated for each subject. Mean change from baseline is defined as the mean of the change in NGAL for each subject at each time point by cohort.

  • Mean change in High Sensitivity C-Reactive Protein (hs-CRP) levels (mg/L) from pre-PTRA to immediately post-PTRA and 15 hours, 27 hours and 8 weeks post-PTRA, with and without Bendavia. [ Time Frame: Pre-PTRA to immediately post-PTRA and 15 hours, 27 hours and 8 weeks post-PTRA ] [ Designated as safety issue: No ]
    Assay of serum for hs-CRP levels will be performed on samples at pre-PTRA, immediately post-PTRA, 15 and 27 hours post-PTRA and 8 weeks post-PTRA. Change in hs-CRP levels from baseline to all post-PTRA time points will be calculated for each subject. Mean change from baseline is defined as the mean of the change in hs-CRP for each subject at each time point by cohort.

  • Mean change in partial pressure of blood oxygen (PO2) values (mmHg) 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 ] [ Designated as safety issue: No ]
    Assay of whole blood for PO2 levels will be performed on samples at pre-PTRA, immediately post-PTRA and 8 weeks post-PTRA. Change in PO2 levels from baseline to post-PTRA time points will be calculated for each subject. Mean change from baseline is defined as the mean of the change in PO2 values for each subject at each time point by cohort.

  • Mean change in Plasma Renin Activity (PRA) levels (ng/ml/hr) 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 ] [ Designated as safety issue: No ]
    Assay of plasma for PRA levels will be performed on samples at pre-PTRA, immediately post-PTRA and 8 weeks post-PTRA. Change in PRA 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 PRA for each subject at each time point by cohort.

  • Mean Change in Systolic Blood Pressure (SBP) values (mmHg) from pre-PTRA, immediately post-PTRA, 27 hours and 8 weeks post-PTRA, with and without Bendavia. [ Time Frame: Pre-PTRA, immediately post-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA ] [ Designated as safety issue: No ]
    Measurement of blood pressure by automated sphygmomanometry for SBP values will be performed at pre-PTRA, immediately post-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA. Changes in SBP values from baseline to post-PTRA time points will be calculated for each subject. Mean change from baseline is defined as the mean of the change in SBP for each subject at each time point by cohort.

  • Mean Change in Diastolic Blood Pressure (DBP) values (mmHg) from pre-PTRA, immediately post-PTRA, 27 hours and 8 weeks post-PTRA, with and without Bendavia. [ Time Frame: Pre-PTRA, immediately post-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA ] [ Designated as safety issue: No ]
    Measurement of blood pressure by automated sphygmomanometry for DBP values will be performed at pre-PTRA, immediately post-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA. Changes in DBP values from baseline to post-PTRA time points will be calculated for each subject. Mean change from baseline is defined as the mean of the change in DBP for each subject at each time point by cohort.

  • Number of adverse events observed with and without Bendavia [ Time Frame: Pre-PTRA through to End of Study Visit (8 weeks post-PTRA) ] [ Designated as safety issue: Yes ]
    Adverse events will be tabulated by treatment group. No statistical analysis will be performed.

  • Mean change in serum sodium levels (mmol/l) from pre-study drug administration (and pre-PTRA), and then at 3, 9, 15, 21, and 27 hours post-PTRA, with and without Bendavia. [ Time Frame: Pre-study drug administration (and pre-PTRA), and then at 3, 9, 15, 21, and 27 hours post-PTRA ] [ Designated as safety issue: Yes ]
    Assay of serum sodium levels will be performed on samples from pre-study drug administration (and pre-PTRA), then at 3, 9, 15, 21, and 27 hours post-PTRA. Change in serum sodium levels from baseline to post-PTRA time points will be calculated for each subject. Mean change from baseline is defined as the mean of the change in serum sodium for each subject at each time point by cohort.

  • Mean change in urine sodium levels (mmol/l) from pre-study drug administration (and pre-PTRA), and then at 3, 9, 15, 21, and 27 hours post-PTRA, with and without Bendavia. [ Time Frame: Pre-study drug administration (and pre-PTRA), and then at 3, 9, 15, 21, and 27 hours post-PTRA ] [ Designated as safety issue: Yes ]
    Assay of urine sodium levels will be performed on samples from pre-study drug administration (and pre-PTRA), then at 3, 9, 15, 21, and 27 hours post-PTRA. Change in urine sodium levels from baseline to post-PTRA time points will be calculated for each subject. Mean change from baseline is defined as the mean of the change in urine sodium for each subject at each time point by cohort.

  • Mean change in serum osmolality levels (mOsm/kg) from pre-study drug administration (and pre-PTRA), and then at 3, 9, 15, 21, and 27 hours post-PTRA, with and without Bendavia. [ Time Frame: Pre-study drug administration (and pre-PTRA), and then at 3, 9, 15, 21, and 27 hours post-PTRA ] [ Designated as safety issue: Yes ]
    Assay of serum osmolality levels will be performed on samples from pre-study drug administration (and pre-PTRA), then at 3, 9, 15, 21, and 27 hours post-PTRA. Change in serum osmolality levels from baseline to post-PTRA time points will be calculated for each subject. Mean change from baseline is defined as the mean of the change in serum osmolality for each subject at each time point by cohort.

  • Mean change in urine osmolality levels (mOsm/kg) from pre-study drug administration (and pre-PTRA), and then at 3, 9, 15, 21, and 27 hours post-PTRA, with and without Bendavia. [ Time Frame: Pre-study drug administration (and pre-PTRA), and then at 3, 9, 15, 21, and 27 hours post-PTRA ] [ Designated as safety issue: Yes ]
    Assay of urine osmolality levels will be performed on samples from pre-study drug administration (and pre-PTRA), then at 3, 9, 15, 21, and 27 hours post-PTRA. Change in urine osmolality levels from baseline to post-PTRA time points will be calculated for each subject. Mean change from baseline is defined as the mean of the change in urine osmolality for each subject at each time point by cohort.

  • Mean change in plasma Arginine Vasopressin (AVP) levels (pg/ml) from pre-study drug administration (and pre-PTRA), and then at 3, 9, 15, 21, and 27 hours post-PTRA , with and without Bendavia. [ Time Frame: Pre-study drug administration (and pre-PTRA), and then at 3, 9, 15, 21, and 27 hours post-PTRA ] [ Designated as safety issue: Yes ]
    Assay of plasma AVP levels will be performed on samples from pre-study drug administration (and pre-PTRA), then at 3, 9, 15, 21, and 27 hours post-PTRA. Change in AVP levels from baseline to post-PTRA time points will be calculated for each subject. Mean change from baseline is defined as the mean of the change in AVP for each subject at each time point by cohort.

  • Mean difference in Bendavia Area Under the Curve(0-infinity) (AUC) when Bendavia is administered in patients undergoing PTRA and healthy volunteers (historical data will be used to provide AUC for Bendavia in healthy volunteers). [ Time Frame: Pre-drug administration (and Pre-PTRA) through 27 hours post-PTRA ] [ Designated as safety issue: No ]

Estimated Enrollment: 28
Study Start Date: December 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendavia
Bendavia, intravenous infusion, 0.05 mg/kg/hr for a maximum duration of 4 hours.
Drug: Bendavia
Other Name: MTP-131
Placebo Comparator: Placebo
Placebo (no active drug), intravenous infusion, for a maximum duration of 4 hours.
Drug: Placebo

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥40 and ≤80 years old.
  • Patients with hypertension (Systolic Blood Pressure >155 mm Hg) and/or requirement for two or more antihypertensive medications: no restrictions on antihypertensive agents, although loop diuretics will be changed to diluting site agents (e.g. hydrochlorothiazide, indapamide, metolazone) for two weeks prior to study. ARAS patients will be identified based upon radiologic and clinical criteria suggestive of renovascular hypertension and/or hemodynamically significant renovascular disease >60% lumen occlusion (determined by quantitative computed tomography angiography or Doppler ultrasound velocity >200 cm/sec).
  • Have an estimated glomerular filtration rate of ≥15 ml/min/1.73 m2 calculated using the Modification of Diet in Renal Disease (MDRD) formula.
  • Have no contraindications to angiography such as severe contrast allergy.
  • Have no contraindications to non-contrast magnetic resonance evaluations such as a pacemaker or magnetically active metal fragments.
  • Able to comply with protocol.
  • Women of childbearing age must:
  • Have a negative pregnancy serum human chorionic gonadotropin test prior to receiving study drug.
  • Agree to use two forms of contraception for 3 months following receipt of the study drug.
  • Men who are sexually active and able to father a child, must agree to use one of the birth control methods listed below for the entire study and for at least 2 months after receiving the study drug:
  • Barrier methods (such as a condom or diaphragm) used with a spermicide.
  • Hormonal methods used by his partner, such as birth control pills, patches, injections, vaginal ring, or implants.
  • Intrauterine device (IUD) used by his partner.
  • Abstinence (no sex).
  • Competent and able to provide written informed consent

Exclusion Criteria:

  • Advanced chronic kidney disease defined as either Stage 5 or end-stage renal disease requiring dialysis.
  • Have other clinically significant abnormalities or laboratory results that would, in the opinion of the investigators, compromise the safety of the patient including evidence of diabetic ketoacidosis, paraproteinemia, or triglycerides above 600 mg/dL.
  • Clinically significant medical conditions within the six months before administration of Bendavia (e.g., cancer, stroke, myocardial infarction, active angina, congestive heart failure) that would, in the opinion of the investigators, compromise the safety of the patient.
  • Have received an investigational drug within thirty (30) days of baseline.
  • Have a serum sodium <135 mmol/L on the day of, and prior to, the PTRA.
  • Are pregnant or breast feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01755858

Contacts
Contact: Elizabeth A Mead, BSc +16172442800 liz.mead@stealthpeptides.com

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Stealth Peptides Inc.
Investigators
Principal Investigator: Stephen C Textor, MD Mayo Clinic
Study Director: Richard Straube, MD Stealth Peptides Inc.
  More Information

No publications provided

Responsible Party: Stealth Peptides Inc.
ClinicalTrials.gov Identifier: NCT01755858     History of Changes
Other Study ID Numbers: SPIRI-225
Study First Received: December 19, 2012
Last Updated: March 31, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension
Hypertension, Renovascular
Ischemia
Renal Artery Obstruction
Reperfusion Injury
Arterial Occlusive Diseases
Wounds and Injuries
Vascular Diseases
Cardiovascular Diseases
Hypertension, Renal
Kidney Diseases
Urologic Diseases
Pathologic Processes
Postoperative Complications

ClinicalTrials.gov processed this record on August 28, 2014