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

NCT ID: NCT01755858

Last Updated: 2020-08-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2016-05-31

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).

Detailed Description

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 ARAS, who are undergoing percutaneous transluminal angioplasty of the renal artery (PTRA).

The randomization (1:1 active:placebo) was stratified by a diagnosis of diabetes mellitus. Participants received either 0.05 mg/kg/h elamipretide or matching placebo, administered as an IV infusion at 60 mL/h infused 30 minutes before and continued 3 hours after PTRA of the renal artery. After completion of the PTRA and stenting, subjects were to receive standard treatment.

Conditions

Renal Artery Obstruction; Hypertension, Renovascular; Ischemia Reperfusion Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Bendavia

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

Group Type: EXPERIMENTAL

Bendavia

Intervention Type: DRUG

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Bendavia

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

MTP-131; Elamipretide

Eligibility Criteria

Inclusion Criteria

• ≥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

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stealth BioTherapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen C Textor, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Richard Straube, MD

Role: STUDY_DIRECTOR

Stealth BioTherapeutics Inc.

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 28916603 (View on PubMed)

Other Identifiers

SPIRI-225

Identifier Type: -

Identifier Source: org_study_id