Effects of Intravenous Bendavia™ on Reperfusion Injury in Patients Undergoing Angioplasty of the Renal Artery

NCT01755858 | Terminated Phase 1 Results

• 1 other identifier: SPIRI-225
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This was a Phase 2a prospective, single center, randomized, double-blind, placebo-controlled study designed to assess the efficacy, pharmacokinetics, safety and tolerability of IV elamipretide for reduction of reperfusion injury in subjects with Atherosclerotic Renal Artery Stenosis (ARAS), who are undergoing percutaneous transluminal angioplasty of the renal artery (PTRA).

Conditions

Renal Artery Obstruction; Hypertension, Renovascular; Ischemia Reperfusion Injury

Keywords

elamipretide

Outcome Measures

Primary Outcomes (1)

• Change in Mean Glomerular Filtration Rate (GFR), as Measured by Iothalamate Clearance, at Baseline (Pre-percutaneous Renal Artery Angioplasty and 8 Weeks Post-PTRA.

  Change in mean glomerular filtration rate (GFR), as measured by iothalamate clearance, from baseline (pre-percutaneous renal artery angioplasty, or pre-PTRA) and 8 weeks post-PTRA..

  Baseline (pre-PTRA) and 8 weeks post-PTRA

Secondary Outcomes (8)

• Change in Mean Glomerular Flow Rate as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA.

  Baseline (pre-PTRA) and 8 weeks post-PTRA

• Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA

  Baseline (pre-PTRA) and 8 weeks post-PTRA

• Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA

  Baseline (pre-PTRA) and 8 weeks post-PTRA

• Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA.

  Baseline (Pre-PTRA) and 8 (+4) weeks post-PTRA

• Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA

  Baseline (Pre-PTRA) , 27 hours post-PTRA and 8 weeks post-PTRA

Study Arms (2)

Bendavia

EXPERIMENTAL

Bendavia, intravenous infusion, 0.05 mg/kg/hr for a maximum duration of 4 hours.

Drug: Bendavia

Placebo

PLACEBO COMPARATOR

Placebo (no active drug), intravenous infusion, for a maximum duration of 4 hours.

Drug: Placebo

Interventions

Bendavia DRUG

Also known as: MTP-131, Elamipretide

Bendavia

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥40 and ≤80 years old.
• Patients with hypertension (systolic blood pressure \[BP\] \>155 mm Hg) and/or requiring 2 or more antihypertensive medications: no restrictions will be placed on antihypertensive agents, although loop diuretics will be temporarily changed to diluting site agents (eg, hydrochlorothiazide, indapamide, metolazone) prior to each blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) study performed during the trial, unless, in the judgment of the Investigator, the change represents a hazard to the patient. 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Saad A, Herrmann SMS, Eirin A, Ferguson CM, Glockner JF, Bjarnason H, McKusick MA, Misra S, Lerman LO, Textor SC. Phase 2a Clinical Trial of Mitochondrial Protection (Elamipretide) During Stent Revascularization in Patients With Atherosclerotic Renal Artery Stenosis. Circ Cardiovasc Interv. 2017 Sep;10(9):e005487. doi: 10.1161/CIRCINTERVENTIONS.117.005487.

  PMID: 28916603 DERIVED

MeSH Terms

Conditions

Renal Artery Obstruction; Hypertension, Renovascular; Reperfusion Injury

Interventions

arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Hypertension, Renal; Hypertension; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Jim Carr, Pharm.D. Chief Clinical Development Officer
• Organization: Stealth BioTherapeutics, Inc

jim.carr@stealthbt.com

1-617-600-6888

Study Officials

• Stephen C Textor, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Richard Straube, MD

  Stealth BioTherapeutics Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2012
• First Posted: December 24, 2012
• Study Start: December 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: May 1, 2016
• Last Updated: August 11, 2020
• Results First Posted: August 11, 2020

Record last verified: 2020-08

Locations

US (1)