A Physician-Initiated Phase II Clinical Trial of RE-01 (Ex Vivo Cultured Peripheral Blood Mononuclear Cells) for Therapeutic Angiogenesis in Non-Healing Lower Extremity Ulcers (PHOENIX-RE Trial)
A Physician-Initiated Phase II Clinical Trial of RE-01 (Ex Vivo Cultured Peripheral Blood Mononuclear Cells) for Therapeutic Angiogenesis in Non-Healing Lower Extremity Ulcers (PHOENIX-RE Trial)
Matsubara Shinobu
Juntendo University Hospital
3-1-3 Hongo, Bunkyo-ku, Tokyo
+81-3-3813-3111
s.matsubara.fs@juntendo.ac.jp
Matsubara Shinobu
Juntendo University Hospital
3-1-3 Hongo, Bunkyo-ku, Tokyo
+81-3-3813-3111
s.matsubara.fs@juntendo.ac.jp
Recruiting
June. 01, 2026
10
Interventional
randomized controlled trial
open(masking not used)
no treatment control/standard of care control
parallel assignment
treatment purpose
1) Age of 18-85 years
2) WIfI wound grade 1-2, size 0.5 cm^2<=,<=10 cm^2
If there are ulcers on both limbs, the limb with the largest ulcer will be treated.
3) Patients diagnosed with Buerger's disease or collagen diseases [including systemic sclerosis, systemic lupus erythematosus(SLE), dermatomyositis, rheumatoid arthritis, malignant rheumatoid arthritis, and various types of vasculitis (such as polyarteritis nodosa, microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, lupus vasculitis, rheumatoid vasculitis, Takayasu arteritis, and sarcoid vasculitis, etc.)], and additionally diagnosed with ischemic ulcers caused by microvascular disorders, including vasculitis.
4) Patients whose primary condition (the disease causing lower limb ischemia) is well-controlled.
5) Patients in whom, despite 4 weeks of standard therapy for refractory ischemic lower extremity ulcers at the time of consent acquisition, the reduction rate of the largest ulcer area remains less than 50% compared to before treatment initiation, and closure by relatively simple procedures (such as suturing, skin grafting, or local flaps) is judged unlikely even if standard therapy is continued.
6) Patients who cannot undergo revascularization surgery, or the maximum ulcer area reduction rate is less than 50% at 4 weeks after revascularization surgery.
7) Patients who have not smoked within 3 months before consent acquisition and agree to refrain from smoking during the trial period.
8) Provided written consent
9) Comply with the protocol requirements
1) Ischemic ulcer or the ulcers due to Buerger's disease or collagen disease in the other limb, which is non healing or is predicted to have a major amputation
2) Infected ulcer (WIfI infection grade 2<=), or uncontrollable infected ulcer with WIfI infection grade 1
3) Ischemic ulcer with WIfI ischemia grade 3<=
(However, if physiological tests of lower limb function cannot be performed due to pain, patients in whom a pulse sound is detected in the dorsalis pedis artery and posterior tibial artery by Doppler examination are eligible.)
4) Heel ulcer
5) Patients who are expected to require major amputation (at or above ankle disarticulation) during the clinical trial period due to progressive ulcers, gangrene, or sepsis.
6) Patients who underwent minor amputation (at or above the metatarsophalangeal joint disarticulation and below the Lisfranc joint disarticulation) on the target limb during the screening period.
7) Patients who have not passed at least four weeks since bypass surgery, angioplasty, or other surgical treatments on the target limb at the time of obtaining consent.
8) Patients with resting pain, ulcers, or gangrene associated with lower limb ischemia caused by factors other than Buerger's disease or collagen diseases (such as spinal canal stenosis, osteoarthritis of the knee, lumbar spondylosis, arteriosclerosis obliterans, etc.).
9) Ischemic ulcer due to peripheral arterial disease, which is diagnosed with MRI, angiography or CT scan during screening.
10) Patients whose test culture of RE-01 cells during the screening period is expected to yield less than a total dose of 2*10^7cells per 200 mL of blood collected, or whose cell composition is predicted not to meet the release criteria.
11) Patients who are predicted to be unable to endure at least five months of standard therapy from baseline.
12) HbA1c >= 8.0%
13) Severe systemic infection (CRP>5mg/dL)
14) Hemoglobin level of less than 8g/dL
15) Patients who are unable to stand even with a prosthesis due to prior major amputation on the contralateral limb.
16) Patients with severe cardiac dysfunction (NYHA class 3 or 4, or left ventricular ejection fraction less than 35% on echocardiography at screening).
17) Patients receiving drugs with angiogenesis inhibitory effects for the treatment of active diabetic proliferative retinopathy, etc.
18) Patients with malignant tumors or within 5 years after curing malignancy (within 10 years for breast cancer).
(However, patients with adequately treated non-melanoma skin cancer or cervical carcinoma in situ may participate in the trial.)
19) Patients with hematological diseases such as hematologic malignancies, myeloproliferative disorders, or myelodysplastic syndromes.
20) Patients with a history of hypersensitivity to the biological raw materials (human serum albumin, fetal bovine serum) used in the investigational product (RE-01).
21) Pregnant or lactating women, women who may become pregnant and tested positive on a pregnancy test at screening, or men or women unwilling to use contraception during the clinical trial period.
22) Patients who test positive for HIV, active HBV, HCV, HTLV, or syphilis during screening examinations.
23) Patients who have previously received the investigational product (RE-01) or its predecessor (MNC-QQ cells).
24) Patients who are considered to have a life expectancy of less than one year due to comorbidities, etc.
25) Patients with comorbidities such as dementia that are deemed likely to significantly affect the evaluation of the efficacy and safety of the investigational product.
26) Patients who participated in another clinical trial within 90 days prior to obtaining consent (patients who did not receive investigational drugs may participate).
27) Other patients deemed inappropriate for this trial by the principal investigator or other responsible physicians.
18age old over
85age old under
Both
non-healing lower extremity ulcers
While continuing existing standard therapy for refractory ischemic lower extremity ulcers, RE-01 cells will be administered at a total of 8 to 60 sites (with a total dose of 0.26 to 2*10^7 cells), three times at 4-week intervals.
Proportion of Subjects Who Responded by 5 Months After Baseline
(1)The proportion of subjects who responded effectively within 5 months from baseline
(2)Number of days from baseline to complete wound healing
(3)Duration from baseline to major amputation, revascularization, or death
(4)Duration from baseline to major amputation
(5)Duration from baseline to major amputation or death
(6)Status of amputation procedures
(7)Changes in scores based on the Wound, Ischemia, and Foot Infection (WIfI) classification from baseline to each evaluation point
(8)Duration from baseline to surgical procedures for stump formation, flap creation, or skin graft closure
(9)Change in lower limb physiological function test results from baseline to each evaluation point
(10)Change in lower limb ischemic resting pain from baseline to each evaluation point using the visual analogue scale (VAS) and numerical rating scales (NRS)
(11)Amount of analgesic use for alleviating resting pain in the target limb ulcer from baseline to each evaluation point
(12)Change and reduction rate of ulcer size from baseline to each evaluation point
(13)Change in ulcer depth from baseline to each evaluation point
(14)Change in the number of ulcers from baseline to each evaluation point
(15)Duration from baseline to the earliest occurrence of a new ulcer
(16)Change in DESIGN-R 2020 score from baseline to each evaluation point
(17)Change in vascular quality of life questionnaire (VascuQOL) score from baseline to each evaluation point
(18)Change in EuroQol 5 Dimensions 5-Level (EQ-5D-5L) score from baseline to each evaluation point
(19)Success rate of investigational product manufacturing
