a Prospective, Multicenter, Randomized Controlled Trial, With a Non-randomized Sentinel Cohort, Evaluating the Efficacy of Bioxheal, a Single-layer Placental-derived Biologic in Nonhealing Diabetic Foot Ulcers

NCT07852338 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: AB BIOH-26-001 Protocol v4.0IND 32533
• Study Type: interventional
• Target: 253
• Locations: 1 country
• Sites: 1

Brief Summary

BIOxHEAL is an investigational biologic made from donated human amniotic membrane, placed directly on the wound to help it heal. Adults with type 1 or type 2 diabetes who have a foot ulcer that has not healed with standard wound care may be able to join. Participants are assigned by chance to one of two groups: BIOxHEAL plus standard wound care, or standard wound care alone. Both groups visit the clinic once a week for up to 12 weeks, or until the ulcer has fully closed. The main question is whether more ulcers close completely by Week 12 when BIOxHEAL is added to standard care

Conditions

Diabetic Foot Ulcer; Biologic; Amniotic Membrane Placental Allograft

Keywords

Diabetic Foot Ulcer; Chronic Wound Wound Healing

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint - Proportion of Target Ulcers with Complete Closure at Week 12

  The percentage of target ulcers achieving wound healing in 12 weeks. Complete wound healing will be determined by the Investigator and confirmed by blinded, independent evaluators with expertise in wound care

  Baseline to Week 12

Secondary Outcomes (4)

• Proportion of Participants With Complete Closure of the Target Ulcer at Week 8

  Baseline Week 8.

• Mean Percent Change in Target Ulcer Surface Area From Baseline to Week 12

  Baseline to Week 12

• Mean Change in Wound-QoL-17 Global Score From Baseline to Week 12

  Baseline to week 12

• Participants With Major or Minor Lower Extremity Amputation

  Baseline through end of follow-up (approximately Week 24)

Study Arms (3)

Sentinel Cohort: BIOxHEAL + SOC

EXPERIMENTAL

All sentinel cohort participants will receive BIOxHEAL plus SOC. who receive at least one treatment of the biologic plus SOC and complete the treatment period of 12 weeks.

Biological: All sentinel cohort participants will receive biologic plus SOC. who receive at least one treatment of the biologic plus SOC and complete the treatment period of 12 weeks.

Randomized: SOC Alone

ACTIVE COMPARATOR

To determine the efficacy of SOC alone in achieving wound healing of nonhealing diabetic foot ulcers over 12 weeks.

Other: Standard wound care for diabetic foot ulcers

Randomized: BIOxHEAL + SOC

EXPERIMENTAL

Participants in the randomized phase are assigned by randomization (2:1) to BIOxHEAL plus SOC or SOC alone. once weekly for up to 12 weeks or until complete ulcer closure

Biological: Participants in the randomized phase are assigned by randomization (2:1) to BIOxHEAL plus SOC or SOC alone. once weekly for up to 12 weeks or until complete ulcer closure

Interventions

All sentinel cohort participants will receive biologic plus SOC. who receive at least one treatment of the biologic plus SOC and complete the treatment period of 12 weeks. BIOLOGICAL

BIOxHEAL is a sterile, single-use biologic derived from human amniotic membrane. It retains the native extracellular matrix structure and naturally occurring biologically active factors of the tissue. It is applied topically to the target ulcer once weekly, together with standard of care, for up to 12 weeks or until complete closure. At each visit, the investigator selects the presentation size that covers the entire ulcer surface without unnecessary excess. Each unit is individually packaged for single-patient, one-time use.

Sentinel Cohort: BIOxHEAL + SOC

Standard wound care for diabetic foot ulcers OTHER

Standard wound care for diabetic foot ulcers: sharp debridement as clinically indicated; wound cleansing with normal saline; moist wound environment using protocol-specified dressings; offloading of plantar ulcers with a device approved by the Medical Monitor; optimization of glycemic control with the participant's providers; nutritional assessment and counseling; and smoking-cessation counseling for current smokers.

Randomized: SOC Alone

Participants in the randomized phase are assigned by randomization (2:1) to BIOxHEAL plus SOC or SOC alone. once weekly for up to 12 weeks or until complete ulcer closure BIOLOGICAL

Standard wound care for diabetic foot ulcers: sharp debridement

Randomized: BIOxHEAL + SOC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Diagnosis of type 1 or type 2 diabetes mellitus
• At randomization, a target ulcer with a surface area of 1.0 cm² to 25.0 cm², measured after debridement
• Target ulcer present for at least 4 weeks and no more than 52 weeks of standard of care before the first screening visit
• Target ulcer located on the foot, with at least 50% of the ulcer below the malleolus
• Target ulcer is Wagner grade 1, extending at least through the dermis or subcutaneous tissue
• Adequate blood flow to the affected limb, confirmed within 3 months of the first screening visit by any one of the following:
• Ankle-brachial index (ABI) of 0.7 to 1.3
• Toe-brachial index (TBI) of 0.6 or higher \* Transcutaneous oxygen measurement (TcPO2) of 40 mmHg or higher
• Arterial Doppler ultrasound showing biphasic dorsalis pedis and posterior tibial flow at the ankle of the affected limb
• If two or more ulcers are present, they are at least 2 cm apart (the largest eligible ulcer is the target ulcer)
• Agrees to use the prescribed offloading method for the whole study
• Agrees to attend the weekly study visits
• Willing and able to take part in the informed consent process

You may not qualify if:

• Life expectancy of less than 6 months
• Target ulcer not caused by diabetes
• Infected target ulcer, or cellulitis of the surrounding skin
• Osteomyelitis of the target ulcer, based on clinical assessment supported by at least one of the following:
• Imaging consistent with osteomyelitis (e.g., X-ray, MRI or nuclear medicine study)
• Positive bone culture
• Abnormal inflammatory markers (e.g., ESR, CRP) with clinical signs highly suggestive of osteomyelitis, in the Investigator's judgment
• Infection of the target ulcer or elsewhere that requires systemic antibiotics
• Current use of immunosuppressants (including systemic corticosteroids above 10 mg prednisone per day or equivalent) or cytotoxic chemotherapy
• Topical steroids applied to the ulcer within 1 month before the first screening visit
• Previous partial amputation of the affected foot, if the resulting deformity prevents proper offloading of the target ulcer
• HbA1c of 12% or higher within 3 months before the first screening visit
• Target ulcer area decreased by more than 20% in the 2 weeks before the first screening visit
• Target ulcer area decreases by 25% or more during the screening period on standard of care (from the first screening visit to the randomization visit)
• Acute Charcot foot, or inactive Charcot foot that prevents proper offloading of the target ulcer

Sponsors & Collaborators

• Applied Biologics, LLC: lead

Study Sites (1)

NOMS Ankle and Foot Care Center

Boardman, Ohio, 44512, United States

RECRUITING

Related Links

• Applied Biologics is a fully-integrated life sciences company providing research, product development, manufacturing and distribution of medical technologies. Since 2010, we've been dedicated to providing doctors innovative biologic solutions to deliver

MeSH Terms

Conditions

Diabetic Foot

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Officials

• Charles Zelen, DPM

  Professional Education & Research Institute (PERI)

  STUDY DIRECTOR

Central Study Contacts

susan A weins, RN

CONTACT

2505142586; susan.weins@appliedbiologics.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-label. Participants, care providers and investigators know the assigned treatment. Complete wound closure is confirmed by blinded, independent wound evaluators with expertise in wound care
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 3, multicenter, prospective, open-label, randomized controlled study at up to 30 U.S. centers. A non-randomized sentinel cohort (5 completed participants required, up to 10 enrolled) first receives BIOxHEAL plus standard of care (SOC) to assess early safety. After Data and Safety Monitoring Board (DSMB) review and FDA approval, 243 participants are randomized 2:1 to BIOxHEAL plus SOC or SOC alone, stratified by baseline ulcer area and ulcer duration. Treatment is given weekly for up to 12 weeks or until complete ulcer closure, which is confirmed 2 weeks later, followed by 3 months of follow-up.

Study Record Dates

• First Submitted: September 25, 2026
• First Posted: October 1, 2026
• Study Start (Estimated): October 8, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: October 1, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)