ACP-01 in Patients With Critical Limb Ischemia

A Randomized Double Blind Placebo Controlled Clinical Study to Assess Blood-Derived Autologous Angiogenic Cell Precursor Therapy in Patients With Critical Limb Ischemia (ACP-CLI)

The primary objective of this study is to determine the efficacy and safety of intramuscular injection of ACP-01, comprised of blood-derived autologous ACPs, in subjects with critical limb ischemia who are receiving standard of care therapy and have no endovascular or surgical revascularization options.

Study Overview

• Status: Completed
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Biological: ACP-01; Biological: Placebo

Detailed Description

This prospective, randomized, double-blind, placebo controlled study will assess the efficacy and safety of autologous ACPs administered intramuscularly into the lower extremity of subjects with CLI who lack surgical or endovascular revascularization options.

A total of approximately 95 subjects will be randomized to treatment with ACP-01 or placebo using a 2:1 randomization scheme, respectively, stratified by site.

The study will continue until all subjects treated experience the study event (either de novo gangrene, doubling of wound size, major amputation, or death) or are event-free for at least 26 weeks. Subjects treated will be followed for no longer than 52 weeks.

One futility analysis for potentially stopping study enrollment will be performed.

Subjects treated at each investigative site will provide written informed consent prior to the conduct of any study-related procedures. Thereafter, they will be screened and those meeting the inclusion/exclusion criteria will be enrolled into the trial and undergo all the study procedures including intramuscular injection of the investigational medicinal product (IMP = ACP-01 or placebo). The IMP will be administered in addition to any conventional treatment the subject is receiving.

The control group will receive placebo injections into the lower extremity to ensure blinding of the assessors and the subjects.

The placebo will consist of the same medium used in the ACP product suspension.

The study consists of four periods: Screening period, Treatment period, Acute safety follow-up and Long term follow-up periods. The total duration of study participation, including follow-up, is at least 26 weeks. Subjects will be followed for up to 52 weeks and at least until the last subject has completed his/her 26 week visit.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1K3
      • Vancouver General Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis CTSC Clinical Research Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Rocky Mountain Regional VA Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33126
      • Clinovation Research, LLC
    • Winter Haven, Florida, United States, 33880
      • Clinical Research of Central Florida
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • New Hampshire
    • Lebanon, New Hampshire, United States
      • Dartmouth-Hitchcock Medical Center
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • Moses H. Cone Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hosptial
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist DeBakey Heart & Vascular Center
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc. (CTT)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject is diagnosed with critical limb ischemia.
• Subject has hemodynamic indicators of severe peripheral arterial occlusive disease.
• Subject is not a candidate for standard revascularization treatment options for peripheral arterial disease.
• Subject must be on standard of care medical therapy for peripheral vascular disease.
• Male or female age 18 and above.
• Non-pregnant, non-lactating female.
• Subject is able to understand and provide voluntary signed informed consent.

Exclusion Criteria:

• Uncorrected aorto-iliac occlusive disease.
• Subjects who, in the opinion of the investigator, have a vascular disease prognosis that indicates they would require a major amputation in a time frame shortly after administration of the IMP (investigational drug or placebo).
• Advanced Critical Limb Ischemia (CLI) presenting as severe ischemic or dry gangrene.
• Lower extremity non-treated active infection.
• Hypercoagulable state.
• Subject received a blood transfusion during the previous 4 weeks (to exclude the potential of non-autologous ACPs in the harvested blood).
• Inability to communicate that may interfere with clinical evaluation.
• Recent major non-vascular operation.
• Myocardial infarction or uncontrolled myocardial ischemia or persistent severe heart failure.
• Severe aortic stenosis.
• Renal failure.
• Hepatic failure.
• Anemia.
• Major stroke.
• Diagnosis of malignancy.
• Concurrent chronic or acute infectious disease and uncontrolled infectious symptoms.
• Severe concurrent disease (other than Peripheral Vascular Disease (PAD)).
• Bleeding diathesis.
• Participation at the same time in another investigational product or device study.
• Chronic cytotoxic drug treatment.
• Life expectancy of less than 6 months.
• Subject unlikely to be available for follow-up.
• Acute worsening of CLI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ACP-01; Injection into lower extremity	Biological: ACP-01; Injection into lower extremity
Placebo Comparator: Placebo; Injection into lower extremity	Biological: Placebo; Injection into lower extremity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound Size, Amputation or Survival	Number of subject with doubling of wound size, major amputation or death	Baseline vs. 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Level	Change in pain score according to the Visual Analog Scale (VAS) for Pain. The visual VAS is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between the two ends of the scale-"no pain" on the left end (0 cm) of the scale and the "worst pain" on the right end of the scale (10 cm). Measurements from the starting point (left end) of the scale to the subjects' marks are recorded in centimeters and are interpreted as their pain. The values ar used to track pain progression for a subject and to compare pain between subjects.	Baseline vs. 1 year
Ulcer Size	Change in ulcer size	Baseline vs. 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Dose and Quantity of Analgesic Drugs Used by the Subject		1 - 52 wks
Reduction in Total Hospitalization Time of Subjects Treated With ACP-01 Compared to Subjects Treated With Placebo		1 - 52 wks
Change From Baseline in Quality of Life	Change in quality of life according to the Vascular Quality of Life Questionnaire.	1 - 52 wks
Change From Baseline in Ankle Pressure		1 - 52 wks
Change From Baseline in Toe Pressure		1 - 52 wks

Collaborators and Investigators

• Sponsor: Hemostemix

Publications and helpful links

Helpful Links

• Hemostemix Inc. website

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: September 14, 2015
• First Submitted That Met QC Criteria: September 14, 2015
• First Posted (Estimated): September 16, 2015

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 22, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Stem cells; Peripheral arterial disease; Autologous; Amputation; Vascular disease; Regenerative medicine
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease Attributes; Atherosclerosis; Peripheral Vascular Diseases; Chronic Disease; Peripheral Arterial Disease; Ischemia; Chronic Limb-Threatening Ischemia
• Other Study ID Numbers: HS 12-01.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No