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.

Overview

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.

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.

Eligibility

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