A Feasibility Trial to Investigate the Safety and Between-group Effect Size of Stimulan-VG and Standard of Care (SoC) in Participants With Diabetic Foot Osteomyelitis of the Forefoot.

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the safety and between-group effect size of Stimulan-VG compared to SoC treatment in patients with diabetic foot osteomyelitis (DFO) of the forefoot.

Detailed Description
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This trial is an open-label, multi-center, randomized, controlled feasibility trial. All participants will undergo surgical debridement and receive either Stimulan-VG and an abbreviated course of systemic antibiotic therapy (3 days ±2 days) or a full course (4-6 weeks) of systemic antibiotic therapy. The total duration of study is Approximately 55 weeks.

Official Title
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A Multi-center, Randomized, Controlled Feasibility Trial of Stimulan-VG and Debridement With an Abbreviated Course of Systemic Antibiotics to Debridement and a Full Course of Systemic Antibiotics for the Treatment of Diabetic Foot Osteomyelitis of the Forefoot

Conditions
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Diabetic Foot Osteomyelitis

Intervention / Treatment
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* Drug: Stimulan-VG
* Drug: Systemic Antibiotics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be ≥18 years of age inclusive, at the time of signing the informed consent. Participant has a current diagnosis and is being treated for diabetes mellitus, type 1 or type 2 Participant who requires surgical debridement, but not to the extent that it requires amputation of the toe, metatarsal or ray Participant who has confirmed presence of diabetic foot osteomyelitis (DFO) of the forefoot as evidenced by at least 3 out of 5 of the following: Positive PTB (probe-to-bone) test Presence of draining sinus presumed to be from underlying bone Plain X-ray highly suggestive of or most compatible with osteomyelitis Ulcer present for greater than 30 days Substantially elevated serum marker for inflammation Participant is male or female A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance in from enrollment up to Week 52. Exclusion Criteria: Diabetic foot ulcer on the tip of toes or in any location other than the forefoot (proximal to the metatarsal neck) Acute amputation site (< 30 days post-operatively) Ulcers present for more than 12 months duration Significant peripheral arterial disease: Ankle brachial index ≤ 0.7 mm Hg OR toe pressure ≤ 40 mm Hg OR transcutaneous oximetry ≤ 40 mm Hg Any significant immunocompromising disease Evidence of systemic infection/sepsis associated with osteomyelitis of the forefoot Malignancy that might affect trial interpretation of outcomes or the participant's ability to complete the trial Any other type of infection that would require ongoing systemic antibiotic therapy during trial enrollment History of muscular disorders, such as myasthenia gravis or parkinsonism Any conditions with known hypercalcemia (> 10.3 mg/dl) or posing a significant risk for developing hypercalcemia Antibiotics to manage acute diabetic foot ulcer (DFU) infection within 24 hours prior to screening Antibiotic therapy exceeding 10 days duration within two weeks prior to the washout period Immunologically suppressed or has received systemic administration of corticosteroids at a dose of >10 mg prednisone (or corticosteroid equivalent) for more than 14 consecutive days within the 90 days prior to informed consent Participant has a positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has clinical signs and symptoms consistent with SARS-CoV-2 infection, or positive SARS-CoV-2 test result, had severe course of COVID-19 (extracorporeal membrane oxygenation [ECMO], mechanically ventilated). Current or recent history (within the last 2 years) of active substance abuse Allergy to any component of the investigational product, such as calcium sulfate, glycopeptide antibiotics (vancomycin), or aminoglycoside antibiotics (gentamicin) Ulcers larger than 3.5 cm in diameter Hemoglobin A1c (HbA1c) > 12% DFI defined as severe (grade 4) by the Infectious Diseases Society of America (IDSA) /International Working Group on the Diabetic Foot criteria. Moderate to severe reduction in renal function, defined as estimated glomerular filtration rate (eGFR) of < 44.0 ml/min/1.73 m2 and creatinine ≥ 3.0 mg/dL

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stimulan-VG<br>Participants will receive Stimulan-VG on Day 1 following surgical debridement. Systemic antibiotics for 3 days ± 2 days following the debridement surgery. | Drug: Stimulan-VG<br>* Participants will receive Stimulan-VG via implantation during debridement surgery on Day 1.<br>Drug: Systemic Antibiotics<br>* Participants will receive Antibiotics per site-specific requirements via oral or intravenous route during Pre and post operatively.<br>|
| Active Comparator: Standard of Care<br>Participants will receive Systemic antibiotics for 4-6 weeks following the debridement surgery. | Drug: Systemic Antibiotics<br>* Participants will receive Antibiotics per site-specific requirements via oral or intravenous route during Pre and post operatively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with confirmed absence of clinical signs of osteomyelitis at the index site | Confirmed absence of clinical signs of osteomyelitis at the index site will be assessed via Probe to Bone Test (PTB) absence of draining sinus presumed to be from underlying bone and Plain X-ray at Week 24. | Week 24 | 
| Number of participants with confirmed absence of clinical signs of surgical site infection at the index site | Confirmed absence of clinical signs of surgical site infection at the index site will be assessed via PTB, absence of draining sinus presumed to be from underlying bone and Plain X-ray at Week 24. | Week 24 | 
| Number of participants with no clinical need for further antibiotic therapy for infection at the index site | Need for further antibiotic therapy for infection at the index site will be assessed at Week 24. | Week 24 | 
| Number of participants with no clinical need for further additional surgical procedure or debridement to treat infection at the index site | Need for further additional surgical procedure or debridement to treat infection at the index site will be assessed at Week 24. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ulcer healing per the University of Texas (UT) Staging System for Diabetic Foot Ulcers | The Investigator will assess the ulcer for healing using the UT Staging System for Diabetic Foot Ulcers which grades DFUs by grade (0, I, II, III) and stage (A, B, C, D), depending on the presence or absence of infection and ischemia. The grades are referred to as follows: grade 0 (pre-or post-ulcerative site that has healed), grade 1 (superficial ulcer not involving tendon, capsule, or bone), and grade 2 (ulcer penetrating to tendon or capsule), and grade 3 (ulcer penetrating bone or joint). The patient will be scored based on Grade score and stage score together. Grade 0, stage A considered being low severity, and Grade 3, stage D considered to be more severe. | Week 12 | 
| Number of participants with occurrence of reinfection at the index site | Number of participants with the occurrence of reinfection at the index site will be assessed via PTB, absence of draining sinus presumed to be from underlying bone and Plain X-ray at Week 52. | Week 52 | 
| Number of participants with no clinical need for further antibiotic therapy for infection at the index site | Need for further antibiotic therapy for infection at the index site will be assessed at Week 52. | Week 52 | 
| Number of participants with no clinical need for further additional surgical procedure or debridement to treat infection at the index site | Need for further additional surgical procedure or debridement to treat infection at the index site will be assessed at Week 52. | Week 52 | 
| Relative change from baseline in Cardiff Wound Impact Schedule (CWIS) quality of life assessment | The CWIS is designed and validated to specifically assess the quality of life (QoL) of subjects with chronic wounds (leg ulcers and diabetic foot ulcers (DFU)). This questionnaire contains 47 items divided into four scales: demographic and clinical characteristics (3 items), global health-related quality of life (HRQoL) (1 item), satisfaction with HRQoL (1 item) and impact of the wound on lifestyle. This last scale includes 3 domains: social life (14 items in total, 7 related to stress and 7 to experience), wellbeing (7 items), and physical symptoms and everyday living (24 items in total, 12 related to stress and 12 to experience). All three domains are scored on a 5-point scale, from not at all to always. Thus, the total score includes the patient's perception of the experience and the associated stress. The final score ranges from 0 (poorer QoL) to 100 points (higher QoL) where a high score indicates a positive rating | Week 24 | 
| Number of participants with adverse events | The number of participants with adverse events will be assessed. | Week 52 | 
| Number of participants discontinuing therapy prematurely due to a treatment related event | The number of participants discontinuing therapy prematurely due to a treatment-related event will be assessed during the course of the trial and recorded on the participants electronic case report form (eCRF). | Week 52 | 
| Number of hospitalizations/re-hospitalizations as a result of treatment for osteomyelitis or ulceration at the index site | The number of hospitalizations/re-hospitalizations as a result of treatment for osteomyelitis will be assessed during the course of the trial and recorded on the participants eCRF. | Week 52 | 
| Number of participants undergoing amputation at the index site | The number of participants undergoing amputation at the index site will be assessed during the course of the trial and recorded on the participants eCRF. | Week 52 | 
| Number of systemic antibiotic free days since trial surgery | The total number of days from Day 1 to week 24 without the use of antibiotics. | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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feasibility, between-group effect size, surgical debridement, systemic antibiotic