ICS-001-1

JRCT ID: jRCT2052230115

Registered date:21/10/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: CLTI (ASO or Buerger's disease) with refractory ulcers or ischemic resting pain to existing therapy
• Date of first enrollment: 20/10/2023
• Target sample size: 6
• Study type: Interventional
• Intervention(s): ICS-001 with autologous peripheral blood mononuclear cells collected by apheresis under the administraion of G-CSF (filgrastim, Gran) and plerixafol (Mozobil) is implanted in lower limb ischemia

Outcome(s)

• Primary Outcome: Incidence of adverse events determined to be causally related to protocol treatments defined in this study protocol (Filgrastim (Gran), Plerixafor (Mozovir), apheresis, anesthesia, ICS-001-autologous peripheral blood mononuclear cell-transplantation procedure, peripheral blood mononuclear cells, ICS-001)

Secondary Outcome

Efficacy
(1) WIfI classification (Wound, Ischemia, Foot Infection) grade and Clinical stage
(2) Rutherford classification
(3) Percentage reduction in area of target ulcer* (only for patients with ulcers in the screening phase).
*The area of each ulcer is measured during the screening period, and the ulcer with the largest area in each limb is the target ulcer for evaluation of ulcer area in that limb (target ulcer).
(4) Number of new ulcers that appeared during the observation period
(5) Ankle brachial index (ABI)
(6) Toe brachial pressure index (TBI)
(7) Skin perfusion pressure (SPP)
(8) Transcutaneous partial oxygen pressure (TcPO2)
(9) Absolute claudication distance (ACD)
(10) Initial claudication distance (ICD)
(11) Numerical Rating Scale (NRS)
(12) Analgesic Quantification Algorithm (AQA)
(13) Lower limb major amputation avoidance rate
(14) Avoidance rate of lower limb amputation (major and unplanned minor amputation)
(15) Overall survival
Safety
(1) Adverse events other than primary endpoint
(2) Vital signs
(3) Laboratory values
(4) Adverse events of ICS-001

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

Patients who meet all of the following criteria are eligible:
(1) Patients with arteriosclerosis obliterans (ASO) or Buerger's disease
(2) Patients with confirmed occlusion or stenosis by angiography, MRA, or CTA of the lower extremities within 6 months prior to obtaining consent
(3) Patients with Ischemia grade 2 or higher in WIfI classification
(4) Patients with refractory ulcers of Wound grade 1 in WIfI classification or Wound grade 0 with ischemic rest pain, that are not suitable for revascularization (endovascular treatment or bypass surgery) or that do not heal for more than 4 weeks despite revascularization.
(5) Non-smoker or patients who have stopped smoking for at least 1 month, and are able to quit smoking throughout the study period (only for Buerger's disease patients)
(6) Patients who are more than 20 years old and less than 85 years old at the time of consent, and whose written consent has been obtained

Exclude criteria

Patients who meet any of the following criteria should be excluded:
(1) Patients scheduled for major amputation
(2) Patients with Wound grade 2 or higher in WIfI classification
(3) Patients with Ischema grade 1 or lower in WIfI classification
(4) Patients with Foot infection grade 2 or higher in WIfI classification
(5) Patients who underwent revascularization, sympathectomy/sympathetic ganglion block, cell therapy/gene therapy, or minor amputation for the purpose of CLTI treatment in the lower extremities to which ICS-001 will be implanted within 4 weeks prior to obtaining consent
(6) Patients with poorly controlled ischemic heart disease or heart failure
(7) Patients with poorly controlled diabetes mellitus
(8) Patients with severe hepatic dysfunction
(9) Patients with severe chronic kidney disease (eGFR under 30 mL/min/1.73 m2) (not applicable to hemodialysis patients)
(10) Patients undergoing peritoneal dialysis or post renal transplantation
(11) Patients with a history of serious hypersensitivity or adverse reactions to Filgrastim (Gran), Plerixafol (Mozobil), or Apheresis
(12) Patients with concomitant or pre-existing interstitial pneumonia
(13) Patients with leukemia, myeloproliferative disorders, or myelodysplastic syndrome
(14) Patients who have undergone percutaneous coronary intervention within 2 months prior to obtaining consent
(15) Patients complicated with malignant tumors
(16) Patients with untreated proliferative diabetic retinopathy (modified Davis classification: proliferative retinopathy)
(17) Patients with infectious diseases associated with a fever of 38 degrees or higher
(18) Patients with hypoalbuminemia (albumin level less than 3.0 g/dL)
(19) Patients with low BMI (under 18)
(20) Patients with claudication, pain at rest, skin ulcer, or gangrene due to other factors not caused by the primary disease
(21) Patients with psychiatric disorders that are difficult to control
(22) Patients with clinically problematic splenomegaly
(23) Patients who are participating in other clinical trials or who have not completed a previous clinical trial more than 3 months after the completion of the previous trial
(24) Pregnant women, lactating women, female patients who may be pregnant or planning to become pregnant by the end of the study period, or male patients whose partners wish to become pregnant
(25) Patients who are unlikely to survive beyond 12 months after the date of consent
(26) Other patients who are judged by the investigator or subinvestigator to be inappropriate as subjects for this clinical trial.

Related Information

• Primary Sponsor: Kenichi Yamahara
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development