Bacteriophage Therapy in Patients With Diabetic Foot Osteomyelitis

Study Overview
=================
Brief Summary
-----------------
This is a phase IIa randomized trial designed to evaluate bacteriophage therapy in patients with diabetic foot osteomyelitis.

Detailed Description
-----------------
This study will evaluate the safety and efficacy of bacteriophage therapy in patients with diabetic foot osteomyelitis (DFO). Enrolled patients will have osteomyelitis infections due to Staph aureus. This study will include eligible patients who have undergone or are planning to undergo surgical debridement of DFO.

Official Title
-----------------
Phase 2b Randomized, Parallel, Double-blind, Placebo-Controlled, Repeat Dose, Multi-Site Study for Safety, Tolerability, and Efficacy of Personalized Phage Treatment and SoC for Subjects With Diabetic Foot Osteomyelitis Due to S. Aureus

Conditions
-----------------
Osteomyelitis, Diabetic Foot Osteomyelitis

Intervention / Treatment
-----------------
* Biological: Phage Therapy
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female ≥18 to <85 years of age. Ongoing diagnosis of diabetes. Have undergone or are scheduled to undergo surgical debridement for DFO as part of SoC, with the associated bone culture positive for S. aureus Availability of at least 1 matching phage for S. aureus cultured from the bone culture Receiving SoC treatment for DFO, including antibiotics after debridement and before randomization Meet defined study ulcer requirements as defined in the protocol Adequate circulation to the affected extremity demonstrated within 3 months prior to randomization and no revascularization procedure anticipated History of compliance with prior appointments and treatments in the investigator's opinion and willingness to receive and comply with SOC antimicrobial and clinical treatments for the study ulcer, including offloading Exclusion Criteria: Healing of the ulcer by more than 30% between screening and randomization. Treated with hyperbaric oxygen or cellular/tissue products with 30 days of screening Suspicion of neoplasm associated with the study ulcer or any non-study diabetic ulcer independent of biopsy result. Presence of any cellulitis not localized to the study ulcer. Indwelling hardware at the site of the DFO. Body weight <50 kg. Presence of above ankle ulcer, with >50% above medial malleolus Hemoglobin < 7g/dL Abnormal liver function tests History of underlying liver disease at screening or within last 3 months Positive test for HIV-1 and /or HIV-2 Any other clinically significant or severe disease that in the judgment of the investigator makes the patient unfit for the study or likely to withdraw prematurely from the study, or that could jeopardize the safety of the patient or confound the results of the study. Known allergy to phage products. Pregnant and/or breastfeeding. Immunocompromised at screening in the judgment of the investigator. Taking any systemic or topical antibacterial antibiotic within 2 weeks prior to the start of study treatment, for a condition other than Diabetic Foot Infection and DFO. Taking any antiviral medication within 2 weeks prior to the start of study treatment and up through the last administration of study treatment. Taking and/or receiving any therapies for the study ulcer that are not considered to be SOC. More than 30 days has elapsed between screening and randomization (start of treatment) Participating in another clinical trial within 4 weeks prior to screening. Inability to obtain or provide informed consent or adhere to the protocol in the judgment of the investigator. Once approximately 30% of subjects are enrolled with DFO involving digits, additional subjects will be excluded.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2:1, phage: placebo
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Phage Therapy<br>Bacteriophage therapy will be personalized for each patient dependent on phage susceptibility testing | Biological: Phage Therapy<br>* Bacteriophage therapy will be personalized for each patient dependent on phage susceptibility testing<br>|
| Placebo Comparator: Group 2: Placebo<br>Placebo (normal saline) will be administered using the same schedule and techniques as for Group 1 (phage therapy). | Other: Placebo<br>* Placebo (normal saline)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent area reduction of study ulcer through Week 13 | Percent area reduction of the study ulcer surface area from baseline through Week 13 | Baseline through Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete healing of the study ulcer | Time to complete healing of the ulcer at any time point during the study | Baseline through Week 13 | 
| Time to 85% reduction of C-reactive protein (CRP) | Time to 85% reduction of CRP at any time point during the study | Baseline through Week 13 | 
| Microbiological eradication of the target pathogen | Percentage of patients with microbiological eradication of the target pathogen at each time point during the study. | baseline through Week 13 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes, Osteomyelitis, Foot Infection, Phage Treatment, Bacteriophage, Phage, Bone Infection