Cellular, Acellular, and Matrix-like Products for Diabetic Foot and Venous Leg Ulcers

Overseen By Madison Dunn

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Tiger Biosciences, LLC.

Must not be taking: Immunosuppressants, Chemotherapy, Biologics, others

Disqualifiers: Infection, Osteomyelitis, Pregnancy, Dialysis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

340 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines new treatments for individuals with diabetic foot ulcers and venous leg ulcers that have not healed with standard care. Researchers are testing two products, ACApatch™ and caregraFT™, made from human placental tissue, to determine if they improve wound healing. Participants will receive either one of these treatments alongside standard care or standard care alone. Suitable candidates for the trial include those with diabetes who have a foot ulcer that has not healed for at least four weeks. As a Phase 4 trial, this research aims to understand how these FDA-approved treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressants, certain chemotherapy drugs, or high doses of corticosteroids, you may not be eligible to participate.

What is the safety track record for ACApatch™ and caregraFT™?

In a previous study, ACApatch™, a treatment made from human placental tissue, was applied to patients with venous leg ulcers. The study showed it was generally safe, with most patients not experiencing serious side effects. Another report suggests that while some patients using similar skin treatments might have minor side effects like redness or irritation, serious problems are rare.

For caregraFT™, also made from human placental tissue, research has shown it is generally safe for treating diabetic foot ulcers. Although there is a small risk of infection, most patients tolerate it well.

Both ACApatch™ and caregraFT™ are used for conditions similar to those in the trial. Since this trial is in a later phase, earlier studies have likely already tested these treatments for safety, supporting their safety profile. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study's treatments?

Researchers are excited about ACApatch™ and caregraFT™ because they both utilize human amniotic membrane tissue allografts derived from human placental tissue. Unlike the standard of care for diabetic foot and venous leg ulcers, which typically involves cleaning, debridement, moisture balance, and offloading, these treatments introduce a regenerative approach. The amniotic membrane is rich in growth factors and cytokines, which can promote faster healing and tissue regeneration. This innovative use of placental tissue could offer a more effective solution, potentially reducing healing time and improving patient outcomes compared to traditional methods.

What evidence suggests that this trial's treatments could be effective for diabetic foot and venous leg ulcers?

This trial examines ACApatch™ for its potential to aid wound healing when combined with standard treatment for diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs). Early results suggest it can enhance healing in cases where regular treatment alone was insufficient. Another product under investigation, caregraFT™, also derived from human placental tissue, has been studied for its effectiveness in treating DFUs and VLUs. A review of studies has found that products like caregraFT™ can lead to better healing compared to standard treatments alone. Both ACApatch™ and caregraFT™ remain under study in this trial, but current evidence supports their potential to improve healing in these challenging ulcers. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

Adults over 21 with nonhealing diabetic foot ulcers (DFU) or venous leg ulcers (VLU) that have persisted for 4-52 weeks. DFUs must be on the foot and grade Wagner 1 or 2, VLUs should show less than a 40% size reduction in the last month. Participants need adequate blood flow to the limb and can't be pregnant, have severe diabetes complications, infections at ulcer sites, recent participation in other trials, or conditions affecting wound healing.

Inclusion Criteria

My ulcers are more than 2 cm apart after cleaning.

I am 21 years old or older.

My foot ulcer is classified as mild or moderate.

Exclusion Criteria

My foot ulcer is not caused by diabetes.

(DFU) Subjects with glycated hemoglobin (HbA1c) greater than or equal to 12%

My wound is infected or was recently infected.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either CAMPs plus SOC or SOC alone for the management of nonhealing diabetic foot and venous leg ulcers

12 weeks

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ACApatch™
• caregraFT™

Trial Overview The trial is testing ACApatch™ and caregraFT™ alongside standard treatments against standard treatment alone for chronic ulcers. It's a multicenter study where participants are randomly assigned to receive either one of these products plus usual care or just the usual care to see which approach helps heal ulcers better.

How Is the Trial Designed?

Group I: VLU CAMP 2 + SOC = caregraFT™ + SOC Experimental Treatment 1 Intervention

caregraFT™ is a human amniotic membrane tissue allografts derived from human placental tissue.

Group II: VLU CAMP 1 + SOC = ACApatch™ + SOC Experimental Treatment 1 Intervention

ACApatch™ is a human amniotic membrane tissue allografts derived from human placental tissue.

Group III: DFU CAMP 2 + SOC = caregraFT™ + SOC Experimental Treatment 1 Intervention

caregraFT™ is a human amniotic membrane tissue allografts derived from human placental tissue.

Group IV: DFU CAMP 1 + SOC = ACApatch™ + SOC Experimental Treatment 1 Intervention

ACApatch™ is a human amniotic membrane tissue allografts derived from human placental tissue.

Group V: DFU Standard of Care Active Control 1 Intervention

Standard of care will be cleaning, debridement, ulcer moisture balance, and offloading.

Group VI: VLU Standard of Care Active Control 1 Intervention

Standard of care will be cleaning, debridement, and ulcer moisture balance.

Who Is Running the Clinical Trial?

Tiger Biosciences, LLC.

Lead Sponsor

Trials

8

Recruited

8,000+

SerenaGroup, Inc.

Collaborator

Trials

32

Recruited

3,900+

Published Research Related to This Trial

A literature review of three clinical trials involving 154 patients showed that the human acellular dermal wound matrix (HADWM) significantly reduced the mean healing time of diabetic foot ulcers (DFUs) by 1.7 weeks compared to standard moist wound care.

Patients treated with HADWM had nearly four times the chance of healing their ulcers compared to those receiving standard care, indicating that HADWM could be a more effective option for difficult-to-heal wounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human acellular dermal wound matrix for treatment of DFU: literature review and analysis. Reyzelman, AM., Bazarov, I.[2022]

The E-Matrix, a novel injectable scaffolding matrix derived from porcine collagen, shows promise in accelerating wound healing for diabetic foot ulcers, mimicking fetal tissue repair mechanisms.

In a pilot study involving six patients, the E-Matrix led to an impressive average wound size reduction of 72% within just 2 weeks after injection, indicating its potential efficacy in treating chronic nonhealing wounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial report of the use of an injectable porcine collagen-derived matrix to stimulate healing of diabetic foot wounds in humans. Marston, WA., Usala, A., Hill, RS., et al.[2016]

In a study involving 73 patients with diabetic foot ulcers, treatment with OASIS Wound Matrix resulted in a higher healing rate (49%) compared to Regranex Gel (28%) after 12 weeks, suggesting its potential effectiveness.

While the difference in healing rates was not statistically significant (P = .055), the results indicate that OASIS Wound Matrix is at least as effective as Regranex for treating full-thickness diabetic foot ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trial comparing OASIS Wound Matrix to Regranex Gel for diabetic ulcers. Niezgoda, JA., Van Gils, CC., Frykberg, RG., et al.[2022]

In a 16-week study involving 168 patients, the human acellular dermal matrix DermACELL showed a significantly higher healing rate for diabetic foot ulcers compared to conventional care (67.9% vs 48.1%).

DermACELL also demonstrated a greater average reduction in wound area compared to both conventional care and another acellular dermal matrix, Graftjacket, indicating its potential as an effective treatment option for these ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Healing Rates in a Multicenter Assessment of a Sterile, Room Temperature, Acellular Dermal Matrix Versus Conventional Care Wound Management and an Active Comparator in the Treatment of Full-Thickness Diabetic Foot Ulcers. Walters, J., Cazzell, S., Pham, H., et al.[2020]

The novel autologous homologous skin construct (AHSC) was tested in an open-label study with 11 patients suffering from diabetic foot ulcers (DFUs), showing that all ulcers successfully accepted the graft with no adverse events reported.

Ten out of the eleven DFUs closed completely within 8 weeks, with a median closure time of 25 days and an impressive 83% reduction in wound area at 4 weeks, indicating that AHSC could be an effective single-application treatment for DFUs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete wound closure following a single topical application of a novel autologous homologous skin construct: first evaluation in an open-label, single-arm feasibility study in diabetic foot ulcers. Armstrong, DG., Orgill, DP., Galiano, R., et al.[2022]

CACIPLIQ, a novel heparan sulfate mimetic, was applied locally to 12 patients with type 2 diabetes suffering from chronic foot and lower extremity ulcers, leading to complete healing in all cases after an average of 4.92 months.

The treatment was well tolerated, indicating both safety and promising efficacy for managing difficult-to-heal ulcers in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a New Heparan Sulfate Mimetic Dressing in the Healing of Foot and Lower Extremity Ulcerations in Type 2 Diabetes: A Case Series. Papanas, N., Demetzos, C., Pippa, N., et al.[2017]

In a study of 12 patients with diabetic foot ulcers that did not heal with standard care, 83% achieved complete healing after 12 weeks of treatment with human reticular acellular dermal matrices (HR-ADMs).

The average time to complete wound closure was just 21 days, highlighting the efficacy of HR-ADMs in treating difficult-to-heal ulcers, with a cost of approximately $800 per patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Reticular Acellular Dermal Matrix in the Healing of Chronic Diabetic Foot Ulcerations that Failed Standard Conservative Treatment: A Retrospective Crossover Study. Zelen, CM., Orgill, DP., Serena, TE., et al.[2017]

A meta-analysis of 9 randomized clinical trials with 897 patients found that acellular matrix (AM) therapy significantly improved the complete healing rate of diabetic foot ulcers (DFUs) compared to standard therapy, with higher rates at both 12 weeks (73% vs. 42%) and 16 weeks (56% vs. 36%).

AM therapy not only led to faster healing times but also resulted in fewer adverse events, indicating a favorable safety profile for patients with full-thickness, noninfected, and nonischemic DFUs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Acellular Matrix Therapy for Diabetic Foot Ulcers: A Meta-Analysis of Randomized Clinical Trials. Huang, W., Chen, Y., Wang, N., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06826339

Evaluating Several Cellular, Acellular, and Matrix-like ... To determine the between-arm difference in the proportion of subjects achieving complete closure of nonhealing diabetic foot ulcers and venous leg ulcers with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07223281

Study Details | NCT07223281 | Real-World Effectiveness of ... Secondary outcomes are time-to-healing, early wound improvement (≥50% reduction in wound area by 4 weeks), wound-related complications, and ...

3. univerahealthcare.com univerahealthcare.com/documents/d/global/uni-prv-bioengineered-tissue-products-for-wound-treatment-and-surgical-interventions

Bioengineered Tissue Products for Wound Treatment and ... The database included 1458 diabetic ulcers treated for the first time in 2014 with Apligraf (n=994) or. EpiFix (n=464). After study inclusion ...

4. researchgate.net researchgate.net/publication/397218367_Evaluation_of_amnion_chorion_amnion_placental_allograft_in_the_management_of_nonhealing_diabetic_foot_ulcers_and_venous_leg_ulcers_a_preliminary_case_series_of_the_TIGERCAMP_clinical_trial

a preliminary case series of the TIGERCAMP clinical trial Objective: Previous studies demonstrated that costs paid on behalf of Medicare recipients for diabetic foot ulcers and venous leg ulcers treated ...

5. internationaljournaloftissuerepair.com internationaljournaloftissuerepair.com/index.php/ijtr/article/view/51

a preliminary case series of the TIGERCAMP clinical trial Conclusion: Preliminary findings indicate ACApatch™ may aid SOC in advancing wound clo-sure rates in chronic DFUs and VLUs unresponsive to SOC ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9586828/

A Multicenter, Randomized, Controlled, Clinical Trial ... A multicenter, randomized, controlled, clinical trial evaluating dehydrated human amniotic membrane in the treatment of venous leg ulcers.

7. cms.gov cms.gov/medicare-coverage-database/view/article.aspx?articleid=59824

Response to Comments: Skin Substitute Grafts/Cellular ... Implementation of this LCD will not restrict use of these products for conditions other than diabetic foot ulcers and venous leg ulcers. Services outside the ...

8. molinahealthcare.com molinahealthcare.com/-/media/Molina/PublicWebsite/PDF/Providers/il/Molina-Clinical-Policies/Skin-Substitutes_R.pdf

Molina Clinical Policy Skin Substitutes Policy No. 357 The three most common uses for skin substitutes are for the treatment of venous leg ulcers, diabetic foot ulcers, and burns. Skin substitutes ( ...