Ulcer

Worldwide, hundreds of millions of patients suffer from chronic non-healing wounds. In addition, most people will experience acute wounding at some point in their life. There is a need to develop agents to treat chronic and acute wounds. This need has intensified with the aging of the population, the rising incidence of diabetes and obesity, and the increasing number of patients undergoing treatment with medications that adversely affect wound healing. Through experiments performed on animals with 4-aminopyridine, (currently marketed by Acorda Healthcare, Inc. in slow-release form as AMPYRA®, and available in generic form proposed for use in this study), the investigators found striking effects on wounds in the standard rodent model used in the literature. In these experiments, animals with wounds held open with stents, healed faster with mass-adjusted human doses of 4-AP. All relevant markers of tissue regeneration were augmented with 4-AP treatment. These injuries are considered standard models, used for decades that correlate to those encountered in the human patients. The investigators found that: 1. 4-AP administration over just 21 days led to a large augmentation of wound healing at time points as early as three days post injury. 2. 4-AP treatment was associated with no adverse events in animals at the doses used consistent with our previous applications. 3. Numerous measures of wound healing at the cellular level showed quantifiable improvement with treatment at the tissue level. 4-AP is used in some of the most fragile of neurologically-ailing patients and is currently a mainline treatment in the setting of multiple sclerosis. Multiple sclerosis patients suffer a demyelinating disorder that causes the stripping of the myelin sheath from around neurons in the peripheral and central nervous system. The myelin covering allows for normal conduction of impulses and, without such covering, impulses are small, impaired, impeded, and ineffective. The recognition that crush injuries to nerves do not simply sever the axonal fibers but also demyelinate some population of nerve cells has led to the idea to study the treatment of peripheral nerve traumatic injuries in humans using 4-AP and this continues to be the subject of some of the investigator's other translational work There is extant literature demonstrating the positive effects of electrical stimulation in wound healing. Electrical stimulation of wounds has been shown to be effective in accelerating wound repair for diabetic foot ulcers and other chronic skin ulcers. Direct electrical stimulation of the skin is labor intensive, while 4-AP is more easily administered as an oral therapy. Thus, the recognition that re-innervation may improve healing in the wound bed - and that 4-AP has a differential, clinically relevant effect on nerves and wounds naturally leads to this application.

This investigation is designed as a prospective, open, multi-center, interventional, non-comparative investigation with the aim to follow chronic wound progression for 6 weeks according to local standard of care. Wound progress is a summary endpoint of the total effect of treatment using the non-bordered foam dressing as the absorbent dressing and includes the changes in an objectively measured wound area and subjectively evaluated wound condition. The only included indication is Venous Leg Ulcers (VLU). A total of n=20 participants will be recruited at up to 6 centers within the US and Canada. There will be a total of seven (7) visits to the investigation site for participants during the treatment period: baseline, followed by weekly visits up to six (6) weeks post baseline. During visits, evaluations will be performed to assess wound progression and status, wound dressing properties, as well as Subject pain, comfort, and quality of life. Safety will be assessed at all visits. One target wound per participant will be included in this investigation.

This investigation is designed as a prospective, open, multi-center, interventional, non-comparative investigation with the aim to follow exuding chronic wound progression for 6 weeks according to local standard of care. Wound progress is a summary endpoint of the total effect of treatment using Mepilex Up as the absorbent dressing and includes the changes in an objectively measured wound area and subjectively evaluated wound condition. Two indications will be included: Venous Leg Ulcers (VLU) and Diabetic Foot Ulcers (DFU). A total of n=68 participants, approximately 34 per indication, will be recruited at up to 8 centers in the US. There will be a total of seven (7) visits to the investigation site for participants during the treatment period: baseline, followed by weekly visits up to six (6) weeks post baseline. During visits, evaluations will be performed to assess wound progression and status, wound dressing properties, as well as Subject pain, comfort, and quality of life. Safety will be assessed at all visits. One target wound per participant will be included in this investigation.

At least 216 eligible adult patients with VLU (with a surface area between 2 cm2 and 25 cm2, and wound age between 4 weeks and 12 months), will be randomized. The patients will be treated with IMP (either EX-03 5% or placebo) in a double blinded manner. Total duration of the study is up to 27 weeks: 1. Screening period (2 visits, 7 days apart), 2. Daily Visits Period - Debridement with IMP (up to 8 daily site visits within up to 2 weeks), 3. Weekly Visits Period - wound management (up to 11 visits within up to 10 weeks) + optional wound closure confirmation (up to 2 weeks). Wound will be managed in a standardized manner. 4. Monthly Visits Period - Wound Closure Durability Period of 12 weeks starting after wound closure confirmation (3 visits within 12 weeks). per formed only for wound closed during weekly visits period.

This is an open-label follow up study to evaluate the safety for the subjects with ALLO-ASC-DFU treatment in phase 3 clinical trial (ALLO-ASC-DFU-302) for 24 months. ALLO-ASC-DFU is a hydrogel sheet containing allogenic adipose-derived mesenchymal stem cells. Adipose-derived stem cells have anti-inflammatory effect and release growth factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), which can enhance wound healing and regeneration of new tissue, finally may provide a new option in treating a Diabetic Foot Ulcer.

Hard to heal Chronic wounds affect a significant percentage of patients over their lifetime. For example, diabetic foot ulcers (DFU) are a major health complication that affect up to 15% of individuals with diabetes mellitus over their lifetime. The treatment of hard to heal chronic wounds is extremely challenging as ulcers such as DFUs and Venous Leg Ulcers (VLUs) may not respond to standard of care (SC) treatment and frequently become infected. Advanced wound products like CAMPs have become an important strategy in the treatment of hard-to-heal chronic wounds by trapping and binding the patients' own cells to rebuild the dermis layer of the skin to aid in healing. The study will evaluate the clinical utility of Multiple CAMPs in the closure of hard to heal diabetic foot ulcers and venous leg ulcers in subjects in comparison to Standard of Care treatment.

This study is a multi-center, prospective, controlled clinical study consisting of 100 subjects from up to 30 providers. The subjects receive XPURT and SOC. The target ulcers are evaluated weekly by the investigator. The subject is treated once a week, to receive weekly applications of XPURT + SOC for up to 20 weeks or until the study ulcer has completely closed (i.e. 100% closure as assessed by the investigator and confirmed 2 weeks later at the closure confirmation visit (CCV). One additional visit per week is optional for both arms, for the purpose of changing only (1) the secondary dressing in the XPURT arm or (2) change the standard of care dressing in the control arm.

This study follows a rescue design: patients in the SOC arm who fail to heal during the CAMPX Prospective Multicenter Randomized Controlled Clinical Trial will enter the Rescue trial and receive the study product. Patients enrolled in this trial must still meet medical necessity criteria for cellular, acellular, matrix-like, products (CAMPs) recently published by the Medicare Administrative Contractor's (MAC) in their local coverage determinations (LCD).

This study follows a rescue design: patients in the SOC arm who fail to heal during the BIOCAMP Prospective Modified Dual Platform Multicenter Randomized Controlled Clinical Trial will enter the Rescue trial and receive one of the study products. Patients enrolled in this trial must still meet medical necessity criteria for cellular, acellular, matrix-like, products (CAMPs) recently published by the Medicare Administrative Contractor's (MAC) in their local coverage determinations (LCD).

This clinical trial will assess the effectiveness of HealthTech Wound Care's medical intervention with the use of DermaBind TL™. HealthTech Wound Care will analyze data related to specific endpoints, such as, wound area preservation over time, rate of wound infection over time, rate of wound reoccurrence post-treatment through EOS, the average number of grafts used per subject and incidence of treatment-emergent adverse events. The goal is to determine whether the intervention produces the desired effects. HealthTech Wound Care will use each study subject's historical data in relation to existing treatments when summarizing data. This study is a prospective, multi-center, open-label, single arm clinical trial designed to collect patient outcome data on commercially available dressing/covering for the protection of DFUs or VLUs over a 12-week treatment period. Wound assessment will be conducted by a clinician, Principal Investigator/Sub-Investigator at each site. The study will include adult patients with chronic non-healing wounds that have failed to respond to standard or conservative treatments. These wounds may include diabetic foot ulcers and venous leg ulcers. The treatment period will be 12 weeks, during which DermaBind TL™ will be applied to the affected wound. The study will monitor outcomes related to , wound area protection, infection rates, through EOS, and adverse events. The study involves two phases: Screening and Treatment