Double-blind, randomized, controlled trial of EIM-001 for in patients with Fontaine classification 3 and 4 lower extremity atherosclerosis obliterans

JRCT ID: jRCT2051230091

Registered date:25/08/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: atherosclerosis obliterans
• Date of first enrollment: 01/10/2023
• 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: Improvement to Fontaine Classification II or lower after 24 weeks

Secondary Outcome

1)Change from baseline in Fontaine classification at each time point up to 48 weeks, percent improvement or worsening
2)Change in WIfI classification grade for ulcer, ischemia, and infection at each time point up to 48 weeks
3)Change from baseline in TcPO2 at each assessment time point up to 48 weeks
4)Change from baseline at each assessment time point of the average value of the NRS for the week immediately preceding each time point up to 48 weeks
5)Change from baseline in ulcer size at each assessment time point up to 48 weeks and percentage improvement,
6)Percentage of ulcer resolution at each time point up to 48 weeks
7)Change from baseline at each assessment point in the pain management medication elimination ladder through 48 weeks
8)Percentage improvement of at least one level of the pain management medication elimination ladder at each time point up to 48 weeks
9)Percentage of patients no longer needing pain medications at 24 and 48 weeks
10)Amount of change from baseline in ankle brachial index (ABI) and ankle blood pressure (AP) at each assessment time point up to 48 weeks and percentage of improvement (equal to or more than 1 level in ischemia grade of WIfI classification)
11)Number and percentage of minor and major amputations from initial intervention to 48 weeks (limbs evaluated and not evaluated) and time to amputation
12)Number and percentage of new ulcers (evaluated and non-evaluated limbs) from the initial intervention to 48 weeks, and time to new ulcer development
13)Number and percentage of revascularization procedures (endovascular or surgical bypass) from initial intervention to 48 weeks and time to revascularization procedure (evaluated/non-evaluated limb)

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 will be considered
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 III or IV at the time of enrollment
However, the non-evaluated limb must be free of pain or ulceration at rest.
4)Patients with a TcPO2 of less than 60 mmHg at at least one site on the skin immediately above the dorsal pedal artery of the limb to be evaluated at screening (S1 and S2) and at the endocarp and, if an ulcer is present, at least one site approximately 5 cm near the ulcer
5)Patients with WIfI Wound classification Grade 0-1 at screening (S2)
6)Patients with no local infection requiring treatment (oral or injectable) associated with an ulcer of the limb being evaluated at screening (S2)
7)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, MRA, or echo within 3 months prior to obtaining consent (including distal stenosis or occlusion after endovascular treatment or revascularization of a proximal vessel)
8)Patients with difficult indications for revascularization or patients who have undergone endovascular or surgical bypass surgery at least one month prior to obtaining consent with inadequate efficacy
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 a history of major amputation of the lower extremity (amputation at a higher site, not including the ankle joint)
2)Patients with severe cardiac dysfunction (LVEF less than 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 at screening (S2)
AST or ALT is 2.5 times or more than the upper limit of the facility standard value.
Total bilirubin is 2.5 times higher than the upper limit of the facility standard.
5)Patients with active malignant neoplasms at the time consent is obtained
6)Patients unable to perform assessments due to cognitive impairment
7)Poorly controlled diabetic patients (HbA1C equal to or more than 10.0%)
8)Patients with severe anemia (Hb less than 8 g/dl) at screening (S2)
9)Patients with a history of hypersensitivity or adverse reactions to trafermin (genetical recombination) products or patients with contraindications to fibroblast spray
10)Patients with positive atelocollagen intradermal test or patients with contraindications for Coaken atelocollagen implants
11)Pregnant women, lactating women, and women of childbearing potential (intention)
12)Patients with a history of alcohol or drug dependence within the past year
13)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/clinical study while participating in this study (excluding observational studies)
14)Patients who have received cell therapy or regenerative medicine treatment within 6 months prior to obtaining consent
15)Other patients deemed inappropriate by the investigator or subinvestigator

Related Information

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