PuraPly AM for Diabetic Foot Ulcers

(PREPARE Trial)

Overseen By Meghan Byrd

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Organogenesis

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

Disqualifiers: Infection, Osteomyelitis, Pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 12 weeks

170 Participants Needed

Trial Summary

What is the purpose of this trial?

This prospective, multi-center, randomized, controlled modified platform Trial compares Purified Native Type 1 Collagen Extracellular Matrix with Polyhexamethylene Biguanide Antimicrobial (PCMP) and Standard of Care versus Standard of Care Alone in subjects with chronic DFUs.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking immunosuppressants, cytotoxic chemotherapy, or hydroxyurea, as these may interfere with wound healing.

What data supports the effectiveness of the treatment PuraPly AM for Diabetic Foot Ulcers?

Research shows that using a collagen-rich hydrogel, similar to the components in PuraPly AM, can effectively inhibit bacterial growth and promote healing in chronic wounds. Additionally, studies on other collagen-based treatments have demonstrated improved healing rates in diabetic foot ulcers compared to standard care. ^{1 2 3 4 5}

Is PuraPly AM safe for use in humans?

The studies on PCMP, which is similar to PuraPly AM, focus on its effectiveness in treating various wounds, but they do not specifically mention any safety concerns, suggesting it is generally considered safe for use in humans. ^{6 7 8 9 10}

What makes the PuraPly AM treatment unique for diabetic foot ulcers?

PuraPly AM is unique because it combines a purified collagen matrix with an antimicrobial agent, polyhexamethylene biguanide, which helps to both support wound healing and prevent infection, unlike standard treatments that may not offer both benefits simultaneously. ^{1 5 11 12 13}

Research Team

Maribel Henao

Principal Investigator

Organogenesis

Eligibility Criteria

This trial is for people with chronic diabetic foot ulcers (DFUs) that haven't healed. Participants should be adults who can follow the study procedures and visit schedules. Those with infected wounds, allergies to collagen or antimicrobial agents used in the study, or other health conditions that could interfere with wound healing are not eligible.

Inclusion Criteria

My foot ulcer is mostly below my ankle.

My ulcer has been present for at least 4 weeks.

I have more than one ulcer, and they are at least 2 cm apart.

Exclusion Criteria

The potential subject is known to have a life expectancy of < 6 months

My ulcer exposes tendon or bone.

I am taking antibiotics for an infection in my ulcer or elsewhere.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomization

Participants are randomized into different treatment groups

1 week

Treatment

Participants receive weekly treatment with either PuraPly AM + SOC, PuraPly XT + SOC, or SOC alone

12 weeks

12 visits (in-person)

Healing Confirmation

A visit to confirm maintenance of complete wound closure for subjects that heal

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Purified Native Type 1 Collagen Extracellular Matrix with Polyhexamethylene Biguanide Antimicrobial (PCMP)

Trial Overview The trial is testing if adding a product called PuraPly AM (which contains purified collagen and an antimicrobial agent) to standard ulcer care helps heal foot ulcers better than just standard care alone. It's a controlled test where patients are randomly chosen to receive either the new treatment plus standard care or only standard care.

Participant Groups

Group I: Standard of Care Experimental Treatment 1 Intervention

Standard of Care (SOC)

Group II: PuraPly AM + SOC Active Control 2 Interventions

PuraPly Antimicrobial Wound Matrix along with standard of care

Group III: PuraPly XT + SOC Active Control 2 Interventions

PuraPly Antimicrobial XT Wound Matrix along with standard of care

Purified Native Type 1 Collagen Extracellular Matrix with Polyhexamethylene Biguanide Antimicrobial (PCMP) is already approved in United States for the following indications:

Approved in United States as PCMP for:

• Management of Nonhealing Diabetic Foot Ulcers

Who Is Running the Clinical Trial?

Organogenesis

Lead Sponsor

Trials

37

Recruited

4,400+

Serena Group

Collaborator

Trials

6

Recruited

790+

Serena Group

Collaborator

Trials

6

Recruited

790+

Findings from Research

In a clinical trial involving 226 patients with hard-to-heal diabetic foot ulcers, the use of fetal bovine acellular dermal matrix (FBADM) alongside standard care resulted in a significantly higher rate of complete wound closure compared to standard care alone (45.6% vs. 27.9%).

FBADM treatment was found to be safe, with no serious adverse events related to the product, and it often achieved wound closure faster, with a median time of 43 days compared to 57 days for standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fetal bovine acellular dermal matrix for the closure of diabetic foot ulcers: a prospective randomised controlled trial. Lantis, JC., Snyder, R., Reyzelman, AM., et al.[2022]

A novel collagen-rich hydrogel derived from human extracellular matrix can effectively deliver antibiotics to chronic wounds, providing sustained release for up to 24 hours while promoting healing and neovascularization.

The hydrogel successfully inhibited bacterial growth and disrupted biofilm formation without causing cytotoxicity to mammalian cells, making it a promising treatment option for chronic wounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Antibiotic Elution in a Collagen-Rich Hydrogel Successfully Inhibits Bacterial Growth and Biofilm Formation In Vitro. Min, JG., Sanchez Rangel, UJ., Franklin, A., et al.[2021]

In a study of 105 diabetic patients with foot ulcers, the use of a collagen bilayer matrix (Integra) showed promise for limb salvage, particularly in patients at low risk for amputation, where only 17% progressed to amputation.

However, in patients identified as high risk for amputation, the collagen matrix did not significantly improve limb salvage rates, with 54% still progressing to amputation, indicating that underlying conditions like poor blood supply and infection heavily influence outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional limb salvage in the diabetic patient: the use of a collagen bilayer matrix and risk factors for amputation. Iorio, ML., Goldstein, J., Adams, M., et al.[2022]

In a study involving 11 patients with chronic diabetic foot ulcers, 82% achieved complete wound closure within 2 to 8 weeks after a single application of the novel decellularized dermal matrix (DDM).

The DDM treatment resulted in significant wound area reduction, with a mean reduction of 87% at 4 weeks, and no adverse events were reported, indicating its safety and potential effectiveness compared to standard care which typically takes 8 to 12 weeks for healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Feasibility and Safety Study of a Novel Human Decellularized Dermal Matrix to Accelerate Healing of Neuropathic Diabetic Foot Ulcers in People With Type 1 and Type 2 Diabetes. Costa, IG., Glazebrook, M., Lu, S., et al.[2022]

In a randomized controlled trial involving 40 participants, the resorbable glass microfiber matrix (BBGFM) significantly improved healing rates of diabetic foot ulcers (DFUs) at 12 weeks, with 70% of wounds healed compared to only 25% in the standard of care group.

The BBGFM group also showed a greater reduction in wound area (79% vs. 37%) and improved neuropathic scores, indicating better overall outcomes without any adverse events related to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multi-centre, single-blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers. Armstrong, DG., Orgill, DP., Galiano, RD., et al.[2022]

In a study of 307 patients with various types of cutaneous wounds, the treatment using purified native type I collagen matrix plus polyhexamethylene biguanide (PCMP) achieved a 73% wound closure rate by week 32.

PCMP treatment resulted in significant reductions in wound area, depth, and volume, with over 80% of wounds showing more than 60% improvement, indicating its effectiveness across different wound types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type I collagen matrix plus polyhexamethylene biguanide antimicrobial for the treatment of cutaneous wounds. Bain, MA., Koullias, GJ., Morse, K., et al.[2021]

In a study of 41 adults with chronic nonhealing wounds, treatment with a native type I collagen matrix combined with the antimicrobial polyhexamethylene biguanide (PCMP) led to a 73% reduction in wound area after 12 weeks, indicating significant efficacy in promoting healing.

Out of the participants, 37% achieved complete wound closure within an average of 6.7 weeks, suggesting that PCMP can be an effective option for managing complex wounds that have not responded to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Native Type I Collagen Matrix Plus Polyhexamethylene Biguanide for Chronic Wound Treatment. Oropallo, AR.[2022]

The RESPOND study, which followed 45 patients with pressure injuries (PIs) for up to 32 weeks, found that the native type I collagen matrix with antimicrobial properties (PCMP) led to complete wound closure in 62% of patients by week 32, demonstrating its effectiveness in managing chronic wounds.

Additionally, 78% of patients experienced a significant reduction in wound area, and 82% showed a substantial decrease in wound volume, indicating that PCMP is a beneficial treatment option for chronic deep wounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of type I collagen matrix plus polyhexamethylene biguanide antimicrobial for the treatment of pressure injuries. Menack, MJ., Thibodeaux, KT., Trabanco, C., et al.[2023]

In a study involving 63 adults with chronic wounds, the use of a porcine collagen matrix embedded with an antimicrobial agent (PCMP) resulted in a significant 68.3% complete wound closure rate, with an average closure time of 5.0 weeks.

PCMP was effective across various wound types, including venous ulcers and surgical wounds, suggesting it can be a valuable addition to standard wound care practices for both chronic and acute wounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Native Type I Collagen with Polyhexamethylene Biguanide Antimicrobial on Wounds: Interim Registry Results. Bain, MA., Thibodeaux, KT., Speyrer, MS., et al.[2023]

In a study of 307 patients with nonhealing wounds, including 67 with venous leg ulcers (VLUs), the use of a collagen matrix with an antimicrobial showed promising results, with wound closure rates increasing from 33% at week 8 to 73% by week 32.

The median time to achieve wound closure for VLUs was 22 weeks, and a significant majority of patients experienced substantial reductions in wound size, with 78% achieving over 60% reduction in area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Noninterventional Study of Type I Collagen Matrix Plus Polyhexamethylene Biguanide Antimicrobial for the Treatment of Venous Leg Ulcers: A Secondary Analysis. Koullias, GJ., Bain, MA., Thibodeaux, K., et al.[2022]

In a study of 34 patients with chronic ulcers, the use of porcine urinary bladder matrix (UBM) led to full healing in all cases, with an average healing time of 9.8 weeks after application.

The study highlights that UBM is effective for treating diabetic and venous ulcers when combined with proper management of risk factors and appropriate dressing techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Porcine urinary bladder matrix: a retrospective study and establishment of protocol. Lecheminant, J., Field, C.[2012]

A new type of hollow fiber membrane made from collagenase-degradable polyurethane ureas (PUUs) has been developed to deliver regenerative factors directly to wounds, promoting healing while allowing for controlled degradation after use.

The optimal formulation, PUU-CL25EG75-peptide, demonstrated effective mechanical strength and the ability to release proteins over 7 days, with complete degradation occurring within 3 days when exposed to collagenase, making it a promising option for wound care applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Collagenase-labile polyurethane urea synthesis and processing into hollow fiber membranes. Fu, HL., Hong, Y., Little, SR., et al.[2014]

In a study involving 61 patients with hard-to-heal diabetic foot ulcers, a chitosan/collagen composite hydrogel dressing significantly reduced ulcer size by an average of 54.5% after four weeks, compared to 38.8% with standard saline-moistened gauze.

The collagen matrix dressing also led to a higher complete healing rate at 20 weeks, with 60% of patients healed compared to only 35.5% in the control group, indicating its potential effectiveness in promoting wound healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of a collagen matrix dressing on a neuropathic diabetic foot ulcer: a randomised control trial. Djavid, GE., Tabaie, SM., Tajali, SB., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Fetal bovine acellular dermal matrix for the closure of diabetic foot ulcers: a prospective randomised controlled trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Topical Antibiotic Elution in a Collagen-Rich Hydrogel Successfully Inhibits Bacterial Growth and Biofilm Formation In Vitro. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Functional limb salvage in the diabetic patient: the use of a collagen bilayer matrix and risk factors for amputation. [2022]

4. Canada pubmed.ncbi.nlm.nih.gov

A Feasibility and Safety Study of a Novel Human Decellularized Dermal Matrix to Accelerate Healing of Neuropathic Diabetic Foot Ulcers in People With Type 1 and Type 2 Diabetes. [2022]

5. England pubmed.ncbi.nlm.nih.gov

A multi-centre, single-blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Type I collagen matrix plus polyhexamethylene biguanide antimicrobial for the treatment of cutaneous wounds. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Use of Native Type I Collagen Matrix Plus Polyhexamethylene Biguanide for Chronic Wound Treatment. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of type I collagen matrix plus polyhexamethylene biguanide antimicrobial for the treatment of pressure injuries. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Effect of Native Type I Collagen with Polyhexamethylene Biguanide Antimicrobial on Wounds: Interim Registry Results. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

A Prospective Noninterventional Study of Type I Collagen Matrix Plus Polyhexamethylene Biguanide Antimicrobial for the Treatment of Venous Leg Ulcers: A Secondary Analysis. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Porcine urinary bladder matrix: a retrospective study and establishment of protocol. [2012]

12. United States pubmed.ncbi.nlm.nih.gov

Collagenase-labile polyurethane urea synthesis and processing into hollow fiber membranes. [2014]

13. England pubmed.ncbi.nlm.nih.gov

Application of a collagen matrix dressing on a neuropathic diabetic foot ulcer: a randomised control trial. [2022]