ACPs in Severe PAD/CLI by Direct Intramuscular Injection

Peripheral Arterial Disease Clinical Trial

Official title:

A Study of Blood-Borne Autologous Angiogenic Cells Precursors Therapy in Patients With Critical Limb Ischemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00523731
• Other study ID #: TV-003
• Secondary ID: ACPs-CLI
• Status: Completed
• Phase: Phase 1
• First received: August 30, 2007
• Last updated: August 30, 2007
• Start date: January 2006
• Est. completion date: March 2007

Study information

• Verified date: February 2007
• Source: TheraVitae Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Study title: A Study of Blood-Borne Autologous Angiogenic Cell Precursors Therapy in Patients with Critical Limb Ischemia ( ACPs-CLI )

Principle Investigator: Assoc.Prof. Pramook Mutirangura,M.D. Head of Division of Vascular Surgery , Department of Surgery, Faculty of Medicine Siriraj Hospital , Mahidol University, BKK,Thailand

Study objective : To determine the safety and efficacy of intramuscular injection of blood-borne autologous ACPs in relieving symptoms of critical limb ischemia of patients treated with maximal medical therapy and don't have intravascular or operative revascularization option.

Study Design : A pilot study , a single center, a non-randomized, open-label trial.

Total expected no. of patients : 6 main selection criteria : A. Subjects will have one or more clinical indications diagnostic of CLI such as: distal extremity pain at rest that requires the subject to use analgesics for >2 weeks; or peripheral ischemic ulcer(s); or areas of gangrene ; or non-healing ischemic ulcers AND

B. Subjects will have one or more of the following hemodynamic indicators of severe peripheral arterial occlusive disease:

I. Ankle brachial index < 0.45 II. Toe brachial index < 0.35 III. TcPO2 / TcO2 of < 40 mmHg. C. The subject is a poor candidate for standard revascularization treatment for peripheral arterial disease, based on inadequate bypass conduit, or unfavorable anatomy D. Age 18 to 80 years

Investigational Product : At D-8 250 ml of blood drawn from the patients for production of autologous EPCs or ACPs (VescellTM). On D0 ,at least 1.5 million ACPs with viability >75 % suspended in 30 ml sterile cell culture medium will be injected 1.5 cm deep and 1.5 apart by a 23 -gauge needle into the gastrocnemius muscle of the leg chosen (ischemic leg) for treatment. For injection planning a grid of 10X10 cm will be prepared and in each point 1 ml of ACPs suspension will be injected.

The study consists of 4 periods: Screening ( D-14 to-9& D-8,Treatment(D0),Acute Safety follow-up (D1&D2),Chronic follow-up (D30 & D90)period ,total follow-up of each case is 3 months.

Evaluation criteria :

Safety : no.& duration of adverse event & serious adverse event Efficacy :Attenuate CLI patients symptoms (Rest pain,Pain-free walking distance,Ulcer size &Gangrene dimension and intensity)

Description:

Six patients with Critical Limb Ischemia (CLI) or severe Peripheral Arterial Disease(PAD) will be enrolled, screened, treated with an injection of Blood-Borne Autologous Angiogenic Cell Precursors(ACPs) in to gastrocnemius of the ischemic leg by intramuscular under regional anesthesia. Following injection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subjects will have one or more clinical indications diagnostic of CLI such as: distal extremity pain at rest that requires the subject to use analgesics for >2 weeks; or peripheral ischemic ulcer(s); or areas of gangrene ; or non-healing ischemic ulcers AND

• Subjects will have one or more of the following hemodynamic indicators of severe peripheral arterial occlusive disease:

• Ankle brachial index < 0.45

• Toe brachial index < 0.35

• TcPO2 / TcO2 of < 40 mmHg.

• The subject is a poor candidate for standard revascularization treatment options for peripheral arterial disease, based on inadequate bypass conduit, or unfavorable anatomy

• Age 18 to 80 years

• Male or non-pregnant, non-lactating female

• Informed consent obtained and consent form signed

Exclusion Criteria:

• Patient having on angiography a meaningful supra popliteal occlusion that may relate to symptoms of CLI.

• Subjects, who in the opinion of the investigator, have a vascular disease prognosis that indicates they would require a major amputation (at or above the ankle) within 4 weeks of start of treatment

• Patient who received blood transfusions during the previous 4 weeks (to exclude the potential of non-autologous ACPs in the harvested blood).

• Inability to communicate (that may interfere with the clinical evaluation of the patient)

• Major operation during the preceding 3 months

• Myocardial infarction or brain infarction or uncontrolled myocardial ischemia or persistent severe heart failure (EF< 25 %) during the preceding 3 months

• Significant valvular disease or after valve replacement during the preceding 3 months

• After heart transplantation

• Severe cardiomyopathy (EF < 25 %)

• Renal failure (creatinine > 2 mg/dl )

• Hepatic failure

• Anemia (lower than 11mg/dl.hemoglobin for female and lower than 12 mg/dl for male)

• Abnormal coagulation tests [platelets, PT (INR), PTT]

• Stroke within the preceding 3 years

• Malignancy within the preceding 3 years

• Concurrent chronic or acute infectious disease

• Severe concurrent medical disease (e.g., septicemia, HIV-1,2/HBV/HCV infections, poorly controlled insulin-dependent diabetes mellitus ; HBA1c >8 % and proliferative retinopathy , systemic lupus erythematosus, multiple sclerosis, amyotrophic lateral sclerosis)

• Chronic immunomodulating or cytotoxic drugs treatment

• Patients who have rectal temp. above 38.40C for 2 consecutive days

• Patient unlikely to be available for follow-up

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Limb Ischemia
• Ischemia
• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Procedure:
• Angiogenic Cell Precursors (ACPs) or Vescell TM

Locations

Country	Name	City	State
Israel	Dr. Valentin Fulga	Tel viv	P.O.B.4049,Ness Ziona

Sponsors (1)

Lead Sponsor	Collaborator
TheraVitae Ltd.

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety		3 months
Primary	Evaluate the safety of ACPs intramuscular injection		3 months
Primary	Efficacy		3 months
Primary	Attenuate CLI patients symptoms as		3 months
Primary	Rest pain		3 months
Primary	Pain-free walking distance		3 months
Primary	Ulcer size		3 months
Primary	Gangrene dimension and intensity		3 months
Primary	Obtain evidence for improvement of tissue perfusion due to ACPs injection		3 months
Secondary	Reduction of CLI patients hospitalization time.		3 months
Secondary	Decrease CLI patient amputation rate.		3 months