Cell Therapy in Critical Limb Ischemia

NCT03994666 | Unknown Phase 2

• 1 other identifier: PO19059
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Study drug and dosage form : Umbilical cord-derived mesenchymal stem cells (HB-MSC1) Dose and route of administration : 60 × 106 cells or 120 x 106 cells to be injected as 30 individual intramuscular injections, once at V0 within 48 hours to 2 weeks maximum after the revascularization procedure. Comparator, dose and route of administration : Placebo, injected as 30 individual intramuscular injections, once at V2 within 48 hours to 2 weeks maximum after the revascularization procedure. Study centers : 3 centers in France Study objectives : Primary: Evaluation of the feasibility and systemic and local tolerance of an implantation, via intramuscular route, of allogenic HB-MSC1, associated with a revascularization procedure, in patients suffering from critical limb ischemia (CLI). Secondary: Preliminary evaluation of efficacy and dose effect relationship of the MSC implantation in hemodynamic, anatomical and functional terms. Exploratory: Constitution of a serum bank of the patients included in the study for inflammation and auto immunity biomarkers analysis Study design : This will be a multicenter Phase IIa study, consisting in a first, open-label, ascending dose feasibility and safety stage followed by a randomized placebo-controlled feasibility, safety and preliminary efficacy stage.

Conditions

Critical Limb Ischemia

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment - emergent adverse events

  The primary safety endpoint will be the occurrence of any high grade AEs (grade 2 and more), either serious or not, assessed as related to the cell implantation by the investigator, reported over the 360 days of the study period. AE Intensity Definition : Grade 1 : asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated ; Grade 2 : minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living ; Grade 3 : severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living ; Grade 4 : life-threatening consequences; urgent intervention indicated ; Grade 5 : death related to adverse event

  Day 1 to day 360

Secondary Outcomes (1)

• Transcutaneous oxygen pressure

  Day 360

Study Arms (3)

simple dose

EXPERIMENTAL

Biological: allogeneic umbilical cord-derived mesenchymal stem cells

double dose

EXPERIMENTAL

Biological: allogeneic umbilical cord-derived mesenchymal stem cells

placebo

PLACEBO COMPARATOR

Biological: Placebo (NaCl)

Interventions

allogeneic umbilical cord-derived mesenchymal stem cells BIOLOGICAL

Injection of mesenchymal stem cells

double dose; simple dose

Placebo (NaCl) BIOLOGICAL

Placebo injection

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient is suffering from critical limb ischemia due to atheromatous arteriopathy, and defined as existence of chronic pain at rest or trophic disorders, with a systolic pressure inferior to 50 mm Hg at the ankle or inferior to 30 mm Hg at the toe (respectively 70 and 50 mm Hg in case of trophic disorder), or a transcutaneous measure of oxygen pressure (TcPO2) at the back of the foot in decubitus inferior to 30 mm Hg, and is being subject to a revascularization procedure, associated or not to minimally invasive surgery.
• The patient (or his/her legal representative(s)) is capable to understand and comply with study requirements and to provide written informed consent prior to any study procedure for participation in the study and transmission of personal "anonymized" data, which signifies an agreement to enter the study and comply with the restrictions and requirements listed in the informed consent form (ICF).
• Male or female patients aged ≥18 years at the time of signing the ICF.
• A female patient is eligible to participate if she is of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal females defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) will be required to use one of the treatment methods that does not modify hemostasis parameters (eg chlormadinone acetate \[Lutéran\]) or must discontinue HRT to allow confirmation of post-menopausal status prior to being enrolled in the study.
• Diabetic patients with an eye fundus examination of less than 3 months excluding proliferative retinopathy
• Patient with a life expectancy \>12 months

You may not qualify if:

• Patients presenting a failure of the revascularization procedure, with technical failure defined as the inability to perform the intended procedure, i.e.
• in the case where femoropopliteal bypass was intended, inability to perform the bypass for any reason
• in the case where endovascular procedure was intended:
• inability to cross the arterial lesion with a guidewire and to catheterize the target vessel
• inability to cross the arterial lesion with any endovascular treatment device such as balloons or stents
• residual stenosis \> 50%
• Patient with non atheromatous arteriopathy The patient has, or has a history of, any significant disease or disorder that would increase the risk for the patient if they were enrolled in the study or would affect study procedures or outcomes.
• The patient is mentally or legally incapacitated.
• Patient protected by law.
• Patient who does not benefit from the national health insurance coverage.
• The patient has been involved in a previous trial with the investigational product.
• History of cancer excepting basocellular epithelioma during the past 5 years.
• Patient necessitating chronic hemodialysis or creatinine clearance inferior to 30 mL/min.
• History of stroke or myocardial infarction of less than 3 months.
• Hemostasis disorder with contra-indication of intramuscular injections.

Sponsors & Collaborators

• CHU de Reims: lead

Study Sites (1)

Damien JOLLY

Reims, France

Location

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Central Study Contacts

Ambroise DUPREY

CONTACT

03 26 78 46 60; aduprey@chu-reims.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: June 21, 2019
• Study Start: September 1, 2019
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: June 21, 2019

Record last verified: 2019-06

Locations

FR (1)