A Prospective, Multi-center, Randomized, Double-blind, Controlled, Phase 1 Study of VELGRAFT, a Living Cellular Construct, in the Management of Chronic Diabetic Foot Ulcers Which Have Attained Granulation Tissue
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
The objective of this study is to evaluate the safety and efficacy of VELGRAFT in patients with chronic diabetic foot ulcers, which have attained granulation tissue. VELGRAFT will be studied in conjunction with pest practices for diabetic foot ulcers. The Primary goal is to assess the safety of VELGRAFT to treat diabetic foot ulcers as compared to standard of care therapy. Secondary goals include the assessment of efficacy of VELGRAFT for healing diabetic foot ulcers compared to standard of care therapy
详细描述
This phase I study is a prospective, randomized, double-blind, active controlled study in up to 24 patients. The study will be conducted in 2 parts: Part A will include 12 patients in a dose escalation scheme to identify the maximum tolerated application of VELGRAFT (up to 4 cohorts, with 3 patients in each cohort), and Part B will include 12 or more patients randomized 1:1 between the VELGRAFT (with the number of applications based on Part A) and control arms. If dose escalation stops prior to Cohort 4 in Part A, meaning less than 12 patients are enrolled in Part A, then the number of patients in Part B will be increased accordingly. For example, if dose escalation stops after Cohort 3 for Part A (i.e., 9 subjects enrolled in Part A), then Part B will include 14 patients (as an even number of patients is needed for 1:1 randomization), for a total of 23 patients in the Phase I study. For all patients, the treatment phase is a 12-week period, in which VELGRAFT or a standard moist dressing will be applied weekly to the DFU. After the treatment phase, there is a final follow-up at 24 weeks. Subject participation is expected to last up to 183 days.
In Part A, eligible patients will enter into the dose escalation scheme, which will include 4 cohorts. Patients in Cohort 1 will receive a total of one application of VELGRAFT, in Cohort 2 will receive a total of two applications of VELGRAFT, in Cohort 3 will receive a total of three applications of VELGRAFT, and in Cohort 4 will receive a total of 4 applications of VELGRAFT.
Three subjects in each cohort will be treated with VELGRAFT based on the escalation scheme as defined below. All the subjects enrolled in a cohort will be monitored continuously for adverse events. The subjects in each cohort will be enrolled in a staggered manner, with a staggering interval of 14 days between subjects to allow for adequate capture of any safety signals.
Decisions to escalate to the next cohort will follow the steps as defined below. Escalations will occur sequentially and after safety is established in the preceding cohort. Enrollment into subsequent cohorts will proceed only after the current cohort has completed 7 days of study treatment and there have been no DLTs or other safety signals observed in the treated patients.
The maximum tolerated application will be the cohort at which no more than one subject experiences a DLT. If 1 subject enrolled in a cohort of 3 experiences a DLT, escalation will be stopped and this level will be considered the maximum tolerated application. If 2 subjects enrolled in a cohort of 3 experience a DLT, the maximum tolerated application will have been exceeded, and the next lower level will be considered the maximum tolerated application. Once the maximum tolerated application is reached, escalation will be stopped. If the maximum tolerated application is not reached even with the highest number of applications, Part A of the study will be stopped and there will be no further escalation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, 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
- •Age ≥ 18 years
- •Patient has current diagnosis of type 1 or type 2 diabetes mellitus
- •Patient's ulcer has been present for greater than 4 weeks and less than 24 weeks at the screening visit
- •Patient's foot ulcer located below malleoli and is between 1-20 cm2 in size on day 1
- •Patient has adequate circulation to the affected extremity, as demonstrated by one of the following within the past 60 days:
- •i. Dorsum transcutaneous oxygen test (TcPO2) with results ≥ 30mmHg, OR ii. ABIs (Ankle brachial index) with results of ≥0.7 and ≤1.2, OR iii. Doppler arterial waveforms, which are triphasic or biphasic at the ankle of affected leg
- •For female patients of childbearing potential, commitment to using a medically accepted means of birth control (i.e., oral, transdermal, or implanted contraceptives, intrauterine device, diaphragm, condom, abstinence, or surgical sterility) throughout study period and tests negative on a pregnancy test
- •Ulcer extends into the dermis or subcutaneous tissue without evidence of exposed muscle, tendon, bone, or joint capsule (Grade 1 by Wagner's scale or Grade A-I by University of Texas Staging System), that has not shown signs of healing despite standard treatment
- •Able and willing to wear an off-loading device or orthopedic shoe
排除标准
- •Gangrene is present on any part of the affected foot
- •Ulcer is of non-diabetic pathophysiology
- •Patient's ulcer is over a Charcot deformity
- •Ulcer total surface area > 20 cm2
- •Osteomyelitis, cellulitis, or other evidence of infection
- •Patient is currently being treated, or received treatment within one month prior, with chemotherapeutic agents, immunosuppressive agents, radiation therapy, or corticosteroids
- •Patient has AIDS, HIV, or cardiac (ejection fraction less than 50% on 2D-ECHO; t-wave inversion on ECG), endocrine (hypothyroidism), disease, or present symptoms/complaints suggestive of gastrointestinal, neurological, or immune disease, that in the opinion of the Investigator, would make the patient an inappropriate candidate for this wound healing study.
- •Patient with any of the below physiological parameters:
- •i. BP systolic >140 or <90 mmHg or diastolic >90 or <60mmHg ii. Pulse <60 or >100bpm iii. Respiratory Rate <9 and >20 bpm iv. Pulse Oximetry <94% in room air v. Temp >100.4 degrees Fahrenheit vi. ALT and AST >2 times the upper limit of normal (ULN) vii. Abnormal bilirubin unless subject has Gilbert's viii. eGFR <60 mL/min/1.73 m2 by CKD-EPI ix. Platelet Count <100,000 x. HbA1c: ≥8.5% xi. Hemoglobin: ≤10g/dL
- •Patients presenting with an ulcer probing to the bone (UT Grade IIIA-D).
- •Patients with Wagner Grades 2-6 ulcers.
- •Patient has had a previous lower extremity amputation.
- •Received allograft, autograft, xenograft, or cellular therapy within 30 days of screening
- •Female patients who are nursing, pregnant, or planning on becoming pregnant during the study period.
- •Patient is unwilling or unable to comply with the postoperative visits necessary for data collection.
- •Patients with known hypersensitivity to the components of the product or shipping medium.
研究组 & 干预措施
Investigational Product
Subject receives applications of VELGRAFT
干预措施: an allogenic cell-based product, containing living human bone marrow-derived mesenchymal stem cells (MSCs) and MSCs differentiated into adipocytes on a porous chitosan-gelatin matrix (Drug)
Control Group
Subject receives Standard of Care treatment
干预措施: Standard of Care of Diabetic Foot Ulcers (Other)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: From Enrollment to End of Follow-Up at 169 days
To assess the safety of VELGRAFT to treat DFUs as compared to standard of care therapy through the difference between the VELGRAFT IP and the control groups for all treated patients in the proportion of patients reporting adverse events during the active study period. The investigator will assess the relationship between study therapy and the occurence of each AE/SAE and will use clinical judgment to determine if there is a reasonable possibility that the IP was responsible for the AE/SAE being reported. Determination of relatedness to the IP will be defined according to one of the following categories: * Definite - The AE/SAE is clearly related to the IP * Probable - The AE/SAE is likely related to the IP * Possible - The AE/SAE may be related to the IP * Unlikely - The AE/SAE is doubtfully related to the IP * Unrelated - The AE/SAE is clearly NOT related to the IP AE/SAE's will be assessed by CTCAE Version 5.0 and safety data of the study will be evaluated by an independent DSMB.
次要结局
- Assess Quality of Life(From Enrollment through study completion, an average of 169 days.)
- Efficacy of VELGRAFT(From Enrollment to weeks 14)
- Wound Closure Rate(From Enrollment to 24 weeks)
- Ulcer Recurrence Rate(Enrollment through study completion at an average of 169 days.)
- Assess Re-epithelialization(From Enrollment through study completion, an average of 169 days)
- Assess scar by scar scales(Enrollment through study completion, an average of 169 days)
- Assess Quality of Life(From screening through study completion, an average of 169 days.)