Assessment of Blood-Borne Autologous Angiogenic Cell Precursors Therapy in Patients With Critical Limb Ischemia

A Randomized Double Blind Placebo Controlled Clinical Study to Assess Blood-Borne Autologous Angiogenic Cell Precursors Therapy in Patients With Critical Limb Ischemia

A randomized, double-blind placebo controlled study to determine the safety and efficacy of Angiogenic Cell Precursors (ACPs) in relieving symptoms of Critical Limb Ischemia in patients treated with standard of care and with no surgical revascularization option. It is assumed that the ACP-treated group will have a lower amputation and death rate as compared to the placebo group. Other hemodynamic, imaging and clinical parameters will also be compared between the two groups. Quality of life assessments will also be performed.

Study Overview

• Status: Suspended
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Drug: Injections

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 (Anticipated): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1K3
      • Vancouver General Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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

Exclusion Criteria:

• Patient having an uncorrected Aorto-Iliac occlusive disease down to the origin of the Profunda-Femoris artery
• Patient who in the opinion of the investigator would require a major amputation within approximately 4 weeks after administration of study treatment.
• Critical Limb Ischemia presenting as severe large ischemic ulcers or dry gangrene proximal to the MTP (Metatarsophalangeal) joints heads or lower extremity wet gangrene
• Lower extremity non-treated active infection
• Hypercoagulable state
• Patient received blood transfusions during the previous 4 weeks
• Patient's condition precludes 2 consecutive attempts of ACPs manufacturing
• Patient unable to communicate
• Major non-vascular operation during the preceding 3 months
• Myocardial infarction or uncontrolled myocardial ischemia or persistent severe heart failure during the preceding 3 months
• Severe aortic stenosis
• Severe renal failure
• Severe hepatic failure
• Anemia
• Major stroke within the preceding 3 months.
• Diagnosis of malignancy within the preceding 3 years
• Concurrent chronic or acute infectious disease and uncontrolled infectious symptoms
• Severe concurrent disease
• Bleeding diathesis.
• Participation at the same time in another stem cell study
• Chronic immunomodulating or cytotoxic drug treatment
• Fever for 2 days prior to the time the patient is about to receive the study treatment
• Life expectancy of less than 6 months
• Patient unlikely to be available for follow-up
• No acute worsening of CLI (Critical Limb Ischemia)

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: Angiogenic Cell Precursors; Intra-muscular injections of Angiogenic Cell Precursors (ACPs) in the ischemic leg	Drug: Injections; Intra-muscular injections
Placebo Comparator: Cell culture medium; Intra-muscular injections of cell culture medium in the ischemic leg	Drug: Injections; Intra-muscular injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to major amputation / mortality	26 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the level of pain in the treated ischemic leg	26 weeks
Change from baseline in the quantity of analgesic drugs used by the patient	26 weeks
Change from baseline in ABI (Ankle Brachial Index)	26 weeks
Change from baseline in TBI (Toe Brachial Index)	26 weeks
Change from baseline in quality of life	26 weeks
Change from baseline in ulcer size	26 weeks
Total hospitalization time of ACP-treated patients compared to controls	26 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of intramuscular injection of ACPs	Vital signs; Physical examination; Clinical laboratory values; Electrocardiograms; Adverse events	26 weeks

Collaborators and Investigators

• Sponsor: Hemostemix
• Investigators: Study Director: Ravi Jain, PhD, Hemostemix Inc.

Publications and helpful links

Helpful Links

• Hemostemix web site

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: May 14, 2014
• First Submitted That Met QC Criteria: May 15, 2014
• First Posted (Estimate): May 16, 2014

Study Record Updates

• Last Update Posted (Actual): May 2, 2019
• Last Update Submitted That Met QC Criteria: April 30, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Autologous; Cell therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: HS 12-01