Double-blind, randomized, controlled trial of EIM-001 for in patients with Fontaine classification IIb lower extremity atherosclerosis obliterans

JRCT ID: jRCT2051220177

Registered date:28/02/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: atherosclerosis obliterans
• Date of first enrollment: 01/03/2023
• Target sample size: 40
• Study type: Interventional
• Intervention(s): The mixture is injected intramuscularly in 40 sites in the perineum (EIM-001 dose is 200 micro-g/body) or saline added atelocollagen at a dose of 0.12 mL per site. The doses should be administered twice with a 2-week interval (20 doses per site).

Outcome(s)

• Primary Outcome: Change from baseline in 6-minute walk distance at 24 weeks

Secondary Outcome

Change in pain-free walking distance with 6-minute walk (change from baseline after 12 and 24 weeks of treatment)
Change from baseline in ankle-brachial index (ABI) and ankle blood pressure (AP) at each assessment time point
Percentage change/improvement in Fontaine classification
Number and percentage of minor and major amputations occurring by 24 weeks (limb being evaluated) and time to amputation
Number and percentage of new ulcers that occurred up to 24 weeks (limb being evaluated) and time to new ulcer development
Number and percentage of revascularization procedures (endovascular and surgical bypass procedures) that occurred up to 24 weeks and the time until the revascularization procedure was reconstructed (limb being evaluated)
Change from baseline in maximum lower leg circumference at 24 weeks

Safety endpoints
Presence, severity, association, and outcome of adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients who meet all of the following selection criteria
1)Patients who are at least 18 years of age at the time consent is obtained
2)For women, patients who meet one of the following criteria and are not of childbearing potential
More than 12 months have passed since the last menstrual period without another medical reason and the patient is considered menopausal
Undergoing permanent sterilization such as bilateral oophorectomy, bilateral tubal ligation, etc.
3)Patients diagnosed with arteriosclerosis obliterans of the lower extremities and belonging to Fontaine classification degree IIb at the time of enrollment
4)Patients capable of exercise loading
5)Patients with stenotic or occlusive lesions below the shallow femoral artery, popliteal artery, or below the knee artery in the limb being evaluated on angiography, CTA or MRA, or echo within 3 months prior to obtaining consent (including distal stenosis or occlusion after endovascular treatment or revascularization of a proximal vessel)
6)Patients with no ulceration in the lower extremities at the time of consent and an ABI of 0.90 or less at screening (S1) or patients with intermittent claudication symptoms in the borderline range of 0.91~1.39
7)Patients with difficult indication for revascularization or patients who have undergone endovascular treatment or surgical bypass surgery at least one month prior to obtaining consent but who have had inadequate effect and who have intermittent claudication at the time of obtaining consent.
8)Patients who have received standard guideline-based drug therapy for at least 4 weeks prior to obtaining consent or patients who have received drug therapy for at least 4 weeks in the past but have not shown improvement in Fontaine classification
9)Patients for whom written consent has been obtained from the individual

Exclude criteria

Patients who meet any one of the following exclusion criteria will not be included.
1)Patients with claudication or rest pain due to factors other than arteriosclerosis obliterans of the lower extremities (spinal canal stenosis, joint disease, autoimmune vasculitis, etc.)
2)Patients with severe cardiac dysfunction (LVEF below 40%) or heart failure (NYHA class II degree or higher)
3)Patients with lethal arrhythmias (unless symptoms are stabilized by pacemaker and ICD implantation or drug therapy)
4)Patients who meet any of the following laboratory criteria
AST or ALT is 2.5 times or more than the upper limit of the facility standard
Total bilirubin greater than 2.5 times the upper limit of the facility standard
5)Patients with active malignant neoplasms at the time consent is obtained
6)Patients whose affected limb with the shortest distance of pain onset changed to the contralateral limb during the screening period
7)Patients unable to perform assessments due to cognitive impairment
8)Poorly controlled diabetic patients (HbA1c equal to or more than 10.0%)
9)Patients with severe anemia (Hb below 8g/dl) at screening (S1 and S2)
10)Patients with a history of hypersensitivity or adverse reactions to trafermin (genetical recombination) products or patients with contraindications to fibrast spray
11)Patients with positive atelocollagen intradermal test or patients with contraindications for Coaken atelocollagen implants
12)Pregnant women, lactating women, and women of childbearing potential (intention)
13)Patients with a history of alcohol or drug dependence within the past year
14)Patients who are participating in another clinical trial/clinical study within 90 days prior to obtaining consent or who plan to participate in another clinical trial while participating in this clinical trial/clinical study (excluding observational studies)
15)Patients who have received cell therapy or regenerative medicine treatment within 6 months prior to obtaining consent
16)Other patients deemed inappropriate by the investigator or subinvestigator

Related Information

• Primary Sponsor: Takao Kato
• Source(s) of Monetary Support: Learning Health Society Institute,FEF Pharmaceutical Co., Ltd