Phase 1 Study of VELGRAFT, a Living Cellular Construct, in the Management of Chronic Diabetic Foot Ulcers Which Have Attained Granulation Tissue

Phase 1RecruitingNCT07498218

Ayu, Inc.24 enrolled

Overview

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

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. In this study, a DLT will be defined as the occurrence of any of the following within 7 days from study drug administration using National Cancer Institute Common Terminology Criteria for adverse Events (NCI CTCAE) version 5.0 criteria, whether related or not to the study treatment. Dose limiting toxicities: * Grade 3 or higher hypersensitivity reactions * Grade 3 or higher rash * Grade 2 or higher skin infection * Any death, except for any death that has been determined by the investigator as unrelated (clearly not related) to the investigational treatment. In Part B of the study, 12 or more patients will be randomized 1:1 between the VELGRAFT treatment arm and control arm. The number of VELGRAFT treatments will be one less application than the maximum tolerated application identified in Part A. For example, if the maximum tolerated application is four (4) applications (one application per week, for 4 consecutive weeks), then the VELGRAFT treatment arm in Part B will include three (3) applications. However, if the maximum tolerated application is one (1) application, then the VELGRAFT treatment arm in Part B will be one (1) application.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 18 years 2. Patient has current diagnosis of type 1 or type 2 diabetes mellitus 3. Patient's ulcer has been present for greater than 4 weeks and less than 24 weeks at the screening visit 4. Patient's foot ulcer located below malleoli and is between 1-20 cm2 in size on day 1 5. 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 6. 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 7. 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 8. Able and willing to wear an off-loading device or orthopedic shoe Exclusion Criteria: 1. Gangrene is present on any part of the affected foot 2. Ulcer is of non-diabetic pathophysiology 3. Patient's ulcer is over a Charcot deformity 4. Ulcer total surface area \> 20 cm2 5. Osteomyelitis, cellulitis, or other evidence of infection 6. Patient is currently being treated, or received treatment within one month prior, with chemotherapeutic agents, immunosuppressive agents, radiation therapy, or corticosteroids 7. 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. 8. 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 9. Patients presenting with an ulcer probing to the bone (UT Grade IIIA-D). 10. Patients with Wagner Grades 2-6 ulcers. 11. Patient has had a previous lower extremity amputation. 12. Received allograft, autograft, xenograft, or cellular therapy within 30 days of screening 13. Female patients who are nursing, pregnant, or planning on becoming pregnant during the study period. 14. Patient is unwilling or unable to comply with the postoperative visits necessary for data collection. 15. Patients with known hypersensitivity to the components of the product or shipping medium.

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

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.

Time frame: From Enrollment to End of Follow-Up at 169 days

Secondary Outcomes

Efficacy of VELGRAFT

To assess the efficacy of VELGRAFT for healing DFUs compared to standard of care therapy. This will be assessed by the difference between the two treatment arms in the proportion of participants with complete wound closure at week 12 and 14. Complete wound closure is defined as complete skin re-epithelialization without drainage or dressing requirements, confirmed at two consecutive study visits, Week 12 and 14. Wounds will be measured by Imito Wound Measurement Software.

Time frame: From Enrollment to weeks 14

Wound Closure Rate

To Evaluate wound closure rate over the course of the trial. This will be measured by the proportion of participants with complete wound closure by 24 weeks.

Time frame: From Enrollment to 24 weeks

Ulcer Recurrence Rate

To measure ulcer recurrence rate over the course of the trial

Time frame: Enrollment through study completion at an average of 169 days.

Assess Re-epithelialization

to Assess Re-epithelialization over the course of the Trial

Time frame: From Enrollment through study completion, an average of 169 days

Assess scar by scar scales

To Assess scar by scar scales via the Patient and Observer Scar Assessment Scale. The Patient and Observer Scar Assessment scale is a 5-point scale. The lowest score is '1', which corresponds to the situation of normal skin (i.e. normal pigmentation, no itching). Score 5 equals the largest difference from normal skin (i.e. the worst imaginable scar or sensation).

Time frame: Enrollment through study completion, an average of 169 days

Assess Quality of Life

To Assess patient reported outcomes for quality of life via patient reported outcomes. Patient reported outcomes include the Wound Pain Visual Analogue Scale and the pruritus Visual Analogue Scale which share a common unit of measurement. The Wound Pain Visual Analogue Scale is a 10-cm (100-mm) straight line, anchored by "no pain" (0) and "worst imaginable pain" (10 or 100 mm), used to objectively measure subjective pain intensity. Patients mark the line to indicate pain levels, with higher scores indicating higher severity and a need for intervention. The Pruritus Visual Analog Scale (VAS) is a validated, subjective 10-cm (100-mm) linear tool used to measure itch intensity, ranging from "no pruritus" (0) to "worst imaginable itch" (10 cm). Patients or owners mark the line to indicate severity, which is then measured to quantify intensity, often categorized as Mild, Moderate, or Severe.

Time frame: From Enrollment through study completion, an average of 169 days.

Assess Quality of Life

To Assess patient reported outcomes for quality of life via patient reported outcomes. Patient reported outcomes include the SF-36 questionnaire, a widely used, self-reported, 36-question survey that measures physical and mental health-related quality of life over the past four weeks. Covering eight health domains, it evaluates functioning, well-being, and limitations, providing scores that, when higher, indicate better health.

Time frame: From screening through study completion, an average of 169 days.

Phase 1 Study of VELGRAFT, a Living Cellular Construct, in the Management of Chronic Diabetic Foot Ulcers Which Have Attained Granulation Tissue

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts