A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose Range Finding Study to Evaluate the Efficacy and Safety of Intramuscular Injection of Human Placenta-Derived Cells (PDA-002) in Subjects With Diabetic Foot Ulcer With and Without Peripheral Arterial Disease.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 159
- 试验地点
- 100
- 主要终点
- Complete wound closure of the index ulcer
研究概览
简要总结
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study evaluating the efficacy and safety of intramuscular administration of human placenta-derived cells (PDA-002) in subjects with diabetic foot ulcers (DFU), including subjects with and without peripheral arterial disease (PAD). Subjects were randomized to receive one of three dose levels of PDA-002 or placebo. Randomization was stratified by PAD status. The study evaluated wound healing and safety outcomes over the follow-up period.
详细描述
This Phase 2 study was designed to evaluate the efficacy and safety of PDA-002, a human placenta-derived cell therapy, administered via intramuscular injection in subjects with diabetic foot ulcers (DFU). The study included subjects with and without peripheral arterial disease (PAD), reflecting a broader DFU population.
Subjects were randomized in a parallel-group design to receive PDA-002 at one of three dose levels (3 × 10^6, 10 × 10^6, or 30 × 10^6 cells) or matching placebo, administered on Study Days 1 and 8. Randomization was stratified by PAD status.
The primary objective was to assess efficacy in terms of wound healing outcomes, with secondary objectives evaluating vascular parameters such as ankle-brachial index (ABI), toe-brachial index (TBI), and transcutaneous oxygen pressure (TcPO2), as well as overall safety.
The study was terminated early due to a business decision; however, subjects were followed according to protocol-defined follow-up schedules.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females, at least 18 years of age or older at the time of signing the informed consent document.
- •Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
- •Able to adhere to the study visit schedule and other protocol requirements.
- •Diabetes mellitus Type 1 or Type
- •Diabetic foot ulcer with severity of Grade 1 (full thickness only) or Grade 2 on the Wagner Grading Scale (Appendix A) of greater than one month duration which has not adequately responded to conventional ulcer therapy with a size of at least of 1cm2 except if present on the toe. The maximum lesion size range in the index ulcer is ≤ 10cm
- •The measurement of the index ulcer is to be evaluated and measured after debridement (if necessary) at the Screening Visit. If located on the plantar aspect of the foot, the index ulcer must be able to be adequately offloaded in the assessment of the investigator.
- •No planned revascularization or amputation over the next 3 months after Screening visit, in the opinion of the Investigator.
- •Screening should not begin until at least 14 days after a failed reperfusion intervention and at least 30 days after a successful reperfusion intervention.
- •Subjects should be receiving appropriate medical therapy for hypertension and diabetes any other chronic medical conditions for which they require ongoing care.
- •A female of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test prior to treatment with study therapy. In addition, sexually active FCBP must agree to use 2 of the following adequate forms of contraception methods simultaneously such as: oral, injectable, or implantable hormonal contraception; tubal ligation; IUD; barrier contraceptive with spermicide or vasectomized partner for the duration of the study and the Follow-up Period.
- •Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP for the duration of the study and the Follow-up Period.
排除标准
- •Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- •Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he or she were to participate in the study.
- •Any condition that confounds the ability to interpret data from the study.
- •Pregnant or lactating females.
- •Subjects with a body mass index > 45 kg/m2 at Screening.
- •AST (SGOT) or ALT (SGPT) > 2.5 x the upper limit of normal (ULN) at Screening.
- •Patient on renal dialysis for abnormal kidney function.
- •An ABI < 0.4 and or TBI < 0.3 in the leg with the index ulcer.
- •Bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease) at Screening.
- •Untreated chronic infection or treatment of any infection with systemic antibiotics, including the ulcer site, must be free of antibiotics within 1 week prior to dosing with IP.
- •Active osteomyelitis, infection, or cellulites at or adjacent to the index ulcer. Patients with a history of being treated for an osteomyelitis without a surgical resection.
- •Index ulcer that has decreased or increased in size by ≥ 30% during the Screening/Run-In/ Pre-Treatment Period.
- •Active Charcot Neuroarthropathy in the foot with the index ulcer
- •Pain at rest due to limb ischemia.
- •Uncontrolled hypertension (defined as diastolic blood pressure > 100 mmHg or systolic blood pressure > 180 mmHg during Screening at 2 independent measurements taken while subject is sitting and resting for at least 5 minutes).
- •Poorly controlled diabetes mellitus (hemoglobin A1c > 12% or a screening serum glucose of ≥ 300mg/dl).
- •Untreated proliferative retinopathy.
- •History of malignant ventricular arrhythmia, CCS Class III-IV angina pectoris, myocardial infarction/ percutaneous coronary intervention (PCI) / coronary artery bypass graft (CABG) in the preceding 6 months prior to signing the informed consent form (ICF), pending coronary revascularization in the following 3 months, transient ischemic attack/cerebrovascular accident in the preceding 6 months, prior to signing the ICF, and/or New York Heart Association [NYHA] Stage III or IV congestive heart failure.
- •Abnormal ECG: new right bundle branch block (BBB) ≥ 120 msec in the preceding 3 months prior to signing the ICF.
- •Uncontrolled hypercoagulation syndrome.
- •Life expectancy less than at 2 years at the time of signing the ICF due to concomitant illnesses.
- •In the opinion of the Investigator, the subject is unsuitable for cellular therapy.
- •History of malignancy within 5 years prior to signing the ICF except basal cell or squamous cell carcinoma of the skin or remote history of cancer now considered cured or positive Pap smear with subsequent negative follow-up.
- •History of hypersensitivity to any of the components of the product formulation (including bovine or porcine products, dextran 40, and dimethyl sulfoxide [DMSO]).
- •Subject has received an investigational agent -an agent or device not approved by the US Food and Drug Administration (FDA) for marketed use in any indication- within 90 days (or 5 half-lives, whichever is longer) prior to treatment with study therapy or planned participation in another therapeutic study prior to the completion of this study.
- •Subject has received previous investigational gene or cell therapy.
研究组 & 干预措施
PDA-002 10 x 10^6 cells
Subjects randomized to receive PDA-002 at a dose of 10 × 10^6 cells administered intramuscularly on Study Days 1 and 8. Randomization was stratified by peripheral arterial disease (PAD) status (subjects with PAD and subjects without PAD).
干预措施: PDA-002 (Biological)
PDA-002 3 x 10^6 cells
Subjects randomized to receive PDA-002 at a dose of 3 × 10^6 cells administered intramuscularly on Study Days 1 and 8. Randomization was stratified by peripheral arterial disease (PAD) status (subjects with PAD and subjects without PAD).
干预措施: PDA-002 (Biological)
PDA-002 30 x 10^6 cells
Subjects randomized to receive PDA-002 at a dose of 30 × 10^6 cells administered intramuscularly on Study Days 1 and 8. Randomization was stratified by peripheral arterial disease (PAD) status (subjects with PAD and subjects without PAD).
干预措施: PDA-002 (Biological)
Placebo
Subjects randomized to receive matching placebo administered intramuscularly on Study Days 1 and 8. Randomization was stratified by peripheral arterial disease (PAD) status.
干预措施: Placebo (Other)
结局指标
主要结局
Complete wound closure of the index ulcer
时间窗: Up to 4 months
Complete wound closure is defined as closure of the index ulcer and retaining wound closure for the subsequent 4 weeks
Safety (adverse events [type, frequency, and severity of AEs, and relationship of AEs to study drug], laboratory abnormalities, and hospitalizations
时间窗: Up to 24 months
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study.
次要结局
- Time to ulcer closure(Up to 6 months)
- Ankle Brachial Index (ABI ) and Toe-Brachial Index (TBI)(Up to 6 months)
- 50% Closure of Index Ulcer(Up to 24 months)
- Transcutaneous oxygen(Up to 6 months)
- Time to amputation, ulcer opening closing, gangrene and infection(Up to 24 months)
- Wagner Grading Scale(Up to 24 months)
- Rutherford Criteria(Up to 6 months)
- 36-item Short Form Health Survey (SF-36)(Up to 6 months)
- Diabetic Foot Ulcer Scale Short Form (DFS-SF) index ulcer(Up to 6 months)
- Patient Global Impression of Change in Neuropathy (PGICN)(Up to 24 months)
- European Quality of Life: EuroQOL-5D- health utility index assessment (EQ-5D)(Up to 6 months)
- Number of all ulcers(Up to 24 months)
- Leg rest pain score(Up to 24 months)