Clinical trial NCT02551679: ACP-01 in Patients With Critical Limb Ischemia
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Critical Limb Ischemia
Keywords: Stem cells
Autologous
Vascular disease
Peripheral arterial disease
Regenerative medicine
Amputation
Lead sponsor: Hemostemix
Sponsor class: INDUSTRY
First posted: 2015-09-16
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Wound Size, Amputation or Survival
timeFrame: Baseline vs. 1 year
Secondary outcomes:
measure: Pain Level
timeFrame: Baseline vs. 1 year
measure: Ulcer Size
timeFrame: Baseline vs. 1 year
Other outcomes:
measure: Change From Baseline in the Dose and Quantity of Analgesic Drugs Used by the Subject
timeFrame: 1 - 52 wks
measure: Reduction in Total Hospitalization Time of Subjects Treated With ACP-01 Compared to Subjects Treated With Placebo
timeFrame: 1 - 52 wks
measure: Change From Baseline in Quality of Life
timeFrame: 1 - 52 wks
measure: Change From Baseline in Ankle Pressure
timeFrame: 1 - 52 wks
measure: Change From Baseline in Toe Pressure
timeFrame: 1 - 52 wks
Locations:
city: Sacramento
country: United States
facility: UC Davis CTSC Clinical Research Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Regional VA Medical Center
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Clinovation Research, LLC
state: Florida
city: Winter Haven
country: United States
facility: Clinical Research of Central Florida
state: Florida
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Greensboro
country: United States
facility: Moses H. Cone Memorial Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Temple University Hosptial
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Houston Methodist DeBakey Heart & Vascular Center
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc. (CTT)
state: Texas
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
References: