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. (BLADE-VG2)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetic Foot Osteomyelitis
• Intervention / Treatment: Drug: STIMULAN VG; Drug: Systemic Antibiotics

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Keira Watts, Clinical Project Manager; Phone Number: +44 (0) 1782 338 580; Email: clinicaltrials@biocomposites.com
• Study Contact Backup: Name: Nicole Villagomez, In-House CRA MCRA; Phone Number: (202) 552-5800; Email: blade-vg2@mcra.com

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85254
      • Recruiting
      • Perseverance Research Center, LLC
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Recruiting
      • NEA Baptist Clinic
  • Florida
    • Miami, Florida, United States, 33137
      • Recruiting
      • Biophase Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant must be ≥18 years of age inclusive, at the time of signing the informed consent.
2. Participant has a current diagnosis and is being treated for diabetes mellitus, type 1 or type 2

3. 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:

   1. Positive PTB (probe-to-bone) test
   2. Presence of draining sinus presumed to be from underlying bone
   3. Plain X-ray or MRI scan highly suggestive of or most compatible with osteomyelitis
   4. Ulcer present for greater than 30 days
   5. Substantially elevated serum marker for inflammation
4. Participant who requires surgical debridement OR Participant who requires amputation of a toe where osteomyelitis is considered to be not fully resected and extends into the metatarsal head.
5. Participant is male or female
6. 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.
7. Participant is capable of giving signed informed consent

Exclusion Criteria:

1. Osteomyelitis of the most distal aspect of the distal phalanx (toe tip)
2. Osteomyelitis in any location other than the forefoot
3. Amputation of the proximal or distal phalanx of the great toe where osteomyelitis is completely contained within the amputated segment
4. Acute amputation site (< 30 days post-operatively)
5. Ulcers present for more than 12 months duration
6. Significant peripheral arterial disease: Ankle brachial index ≤ 0.7 mm Hg OR toe pressure ≤ 40 mm Hg OR transcutaneous oximetry ≤ 40 mm Hg
7. Any significant immunocompromising disease
8. Evidence of systemic infection/sepsis associated with osteomyelitis of the forefoot
9. Malignancy that might affect trial interpretation of outcomes or the participant's ability to complete the trial
10. Any other type of infection that would require ongoing systemic antibiotic therapy during trial enrollment
11. History of muscular disorders, such as myasthenia gravis or parkinsonism
12. Any conditions with known hypercalcemia (> 10.3 mg/dl) or posing a significant risk for developing hypercalcemia (i.e. Hyperparathyroidism)
13. Immunologically suppressed or has received systemic administration of corticosteroids (does not include topical, inhaled or intranasal formulations) at a dose of >10 mg prednisone (or corticosteroid equivalent) for more than 14 consecutive days within the 90 days prior to informed consent
14. Concurrent involvement in a trial of another investigational product
15. Ulcers larger than 3.5 cm in diameter
16. Contra-indication for having a MRI scan
17. Inability to have a MRI scan
18. DFI defined as severe (grade 4) by the Infectious Diseases Society of America (IDSA) /International Working Group on the Diabetic Foot criteria.
19. Hemoglobin A1c (HbA1c) > 12%
20. 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
21. Current or recent history (within last 2 years) of active substance abuse (e.g. recreational drugs, narcotics, or alcohol) that, in the judgment of the investigator, may compromise the ability of the trial participant to adhere to the trial conduct and procedures
22. Previous history of adverse incidents or allergy to any component of the investigational product, such as calcium sulfate, glycopeptide antibiotics (vancomycin), or aminoglycoside antibiotics (gentamicin)
23. The investigator believes trial participation may compromise safety of the participant or the results of the trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care; Participants will receive Systemic antibiotics for 4-6 weeks following the debridement surgery.	Drug: Systemic Antibiotics; Participants will receive Antibiotics per site-specific requirements.
Experimental: STIMULAN VG; 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; Participants will receive STIMULAN VG via implantation during debridement surgery on Day 1.; Drug: Systemic Antibiotics; Participants will receive Antibiotics per site-specific requirements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Number of participants with confirmed absence of clinical signs of osteomyelitis or surgical infection at the index site	Confirmed absence of clinical signs of osteomyelitis or surgical site infection at the index site will be evidenced by Negative Probe to Bone Test (PTB), absence of draining sinus presumed to be from underlying bone and MRI scan 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 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 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 MRI at Week 52.	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 52

Collaborators and Investigators

• Sponsor: Biocomposites Ltd
• Collaborators: MCRA

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2023
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: September 12, 2022
• First Submitted That Met QC Criteria: September 12, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: feasibility; systemic antibiotic; between-group effect size; surgical debridement
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Infections; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Infectious; Foot Ulcer; Diabetic Foot; Osteomyelitis; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: 254915

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No