Bacteriophage Therapy TP-102 in Patients With Diabetic Foot Infection (REVERSE2)

A Phase 2 CT to Evaluate the Safety and Efficacy of Topical Administration of Bacteriophage Therapy TP-102 in Patients With DFI

TP-102 is a novel bacteriophage cocktail comprised of 5 (five) lytic bacteriophages against Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii. TP-102 is being developed for topical treatment of patients with wound infections including chronic ulcers; applied every other day (three times weekly (TIW)).

Study Overview

• Status: Recruiting
• Conditions: Diabetic Foot Infection
• Intervention / Treatment: Biological: TP-102; Other: Placebo

Detailed Description

This is a Phase 2b, double-blinded, randomised, placebo-controlled multicenter study to determine the safety and efficacy of TP-102, in patients with diabetic foot infection.

Eighty (80) patients with an infected diabetic foot ulcer and with at least one target bacterial strain (Pseudomonas aeruginosa, Staphylococcus aureus or Acinetobacter baumannii) susceptible to TP-102.

Patients will be randomised to receive TP-102 or placebo, in a 1:1 ratio. Patients will be treated with 1 (one) mL of IP/ Placebo solution applied topically per cm3 of target ulcer. Patients will be treated with a total of 12 treatments in 28 days (+3 days) with at least one day of interval in between the days of treatment (no consecutive days of treatment are allowed) and a maximum of 3 (three) days without treatment.

The titre of each bacteriophage in TP-102 is 1x109 (>1x108 and < 1x1010) plaque forming units per milliliter (PFU/mL).

Assessments for efficacy and safety will include concomitant medications and AEs, local tolerability, clinical laboratory tests, vital signs, physical examination, wound biopsy/swab to determine the presence, speciation and TP-102 sensitivity of bacteria and target ulcer assessment.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sofia Corte Real; Phone Number: +351215943993; Email: scortereal@technophage.pt
• Study Contact Backup: Name: Margarida Barreto; Email: mbarreto@technophage.pt

Study Locations

• India
  • Chennai, India, 600013
    • Recruiting
    • MV Hospital for Diabetes Pvt. Ltd
    • Contact: G Senthil
  • Kanpur, India
    • Recruiting
    • GSVM Medical College
    • Contact: Sanjay Kala
  • Nagpur, India, 440012
    • Recruiting
    • Crescent Hospital & Heart Centre
    • Contact: Mohammad Qureshi
  • Nashik, India, 422002
    • Recruiting
    • Shree Siddhi Vinayak Hospital
    • Contact: Sachin Arsule
  • Vadodara, India, 390012
    • Recruiting
    • Jupiter Hospital & Research Center
    • Contact: Vikas Matai
  • Vadodara, India, 390020
    • Recruiting
    • Parikh Multispeciality Healthcare Pvt. Ltd
    • Contact: Parikh Niranjan
  • Vadodara, India, 390021
    • Recruiting
    • Aman Hospital & Research Centre
    • Contact: Aman Khanna
  • Vijayawada, India, 520002
    • Recruiting
    • Yalamanchi Hospitals & Research Centers Pvt. Ltd
    • Contact: Yalamanchi Rao
• United States
  • California
    • Los Angeles, California, United States, 90073
      • Not yet recruiting
      • VA Greater LA Healthcare System
      • Contact: Aksone Nouvoung, DPM
    • Vista, California, United States, 92081
      • Not yet recruiting
      • ILD Research Center
      • Contact: Dean Vayser, MD
  • Florida
    • Miami, Florida, United States, 33155
      • Withdrawn
      • Keralty Hospital Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged ≥18 years old;
• Established diagnosis of Diabetes Mellitus (type I or II);
• Glycosylated hemoglobin (HbA1c) value < 12.0%;
• Designated foot infection meets the following criteria:
• Present for at least 3 weeks;
• Below-ankle, full-thickness, cutaneous ulcer;
• Wound area (after debridement, if applicable) 1 to 20.0 cm2;
• PEDIS infection grade 2 or 3;
• PEDIS perfusion grade 1 or 2;
• PEDIS depth grade 1 or 2 (grade 3 at the discretion of the investigator e.g. if they have received appropriate surgical treatment to remove infected bones).
• Diabetic foot infection with at least one target bacterial strain (Pseudomonas aeruginosa, Staphylococcus aureus or Acinetobacter baumannii), susceptible to the TP-102 bacteriophage cocktail, as assessed from wound cultures;
• Patients of suitable physical and mental health as determined by the Investigator on the basis of medical history and general physical examination;
• Patients of childbearing potential must have a negative serum pregnancy test at screening;
• ICF signed voluntarily before any study-related procedure is performed, indicating that the patient understands the purpose of, and procedures required in the study and is willing to participate in the study.

Exclusion Criteria:

• Infected study ulcer less than 2 cm away from other ulcers, in the case of multiple ulcers;
• Patient receiving hyperbaric oxygen therapy (HBOT), negative pressure wound therapy (NPWT), bioengineering skin (BES) substitutes and/or growth factors;
• Patient which, in the opinion of the investigator, may not comply with study related procedures;
• Presence of active malignant or benign tumors of any kind, (with exception to nonmelanoma skin cancer as per investigator's discretion);
• Being pregnant or breastfeeding;
• Currently participating in another clinical trial or having participated in a previous clinical trial with receipt of an investigational product within 30 days of the first administration of IP;
• A condition that, in the opinion of the Investigator, could compromise the well-being of the patient or course of the study, or prevent the patient from meeting or performing any study requirements;
• Participants with hypersensitivity to any component of investigational products.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TP-102; Patients will be randomly assigned in a 1:1 ratio to one of two treatment arms at Day 1. The wound standard of care (SoC) procedures shall be in accordance to each sites normal DFI routine.	Biological: TP-102; Patients randomised to TP-102 will receive 1 (one) mL of IP solution, applied topically per cm3 of target ulcer. The titre of each bacteriophage in TP-102 is 1x109 PFU/mL (>1x108 PFU/mL and <1x1010 PFU/mL). All patients randomised to TP-102 will receive the same concentration per mL. TP-102 will be applied to the target ulcer using a syringe without a needle. The volume of TP-102 to be administered will be determined from the wound volume assessment at the previous visit through an automated wound measurement system (Silhouette), except on the first day of treatment where the amount applied will be determined based on the wound volume determined at that time using the automated wound measurement system (Silhouette).
Placebo Comparator: Placebo; Patients will be randomly assigned in a 1:1 ratio to one of two treatment arms at Day 1. The wound standard of care (SoC) procedures shall be in accordance to each sites normal DFI routine.	Other: Placebo; Patients randomised to placebo, the volume calculated to be administered will be determined from the wound volume assessment at the previous visit through an automated wound measurement system (Silhouette), except on the first day of treatment where the amount applied will be determined based on the wound volume determined at that time using the automated wound measurement system (Silhouette).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. Number and percentage of treatment emergent adverse events (TEAEs)	See above	From baseline to EOT, aproximately 12 weeks
2. Mean DFUWI score (total AUC) for TP-102 versus Placebo	See above	From baseline to EOT, , aproximately 12 weeks
3. Percentage of patients that achieve a 50% reduction in wound surface area by week 4		Week 4

Secondary Outcome Measures

Outcome Measure	Time Frame
1. Change in mean CRP/ESR/PCT/WCC value for TP-102 versus Placebo	From baseline to EOT, , aproximately 12 weeks
2. Percentage of patients with a value over clinical diagnostic cut-off for DFI for CRP/ESR/PCT/WCC	Baseline to EOT, , aproximately 12 weeks
3. Percentage eradication of TP-102 susceptible strains for TP-102 versus Placebo at EOT;	EOT, , aproximately 12 weeks
4. Percentage of patients with target strain not-susceptible to TP-102 for TP-102 versus Placebo at EOT;	EOT, , aproximately 12 weeks

Collaborators and Investigators

• Sponsor: Technophage, SA
• Collaborators: VectorB2B
• Investigators: Principal Investigator: Jose David Suarez, Keralty Hospital, Miami; Principal Investigator: Aksone Nouvong, VA Greater Los Angeles Health Care; Principal Investigator: Sachin Arsule, Shree Siddhi Vinayal Hospital; Principal Investigator: Yalamanchi Rao, Yalamanchi Hospitals & Research Centers Pvt. Ltd; Principal Investigator: Senthil Kumar, MV Hospital for Diabetes Pvt. Ltd; Principal Investigator: Aman Khanna, Aman Hospital & Research Centre; Principal Investigator: Mohammad Qureshi, Crescent Hospital & Heart Centre; Principal Investigator: Parikh Niranjan, Parikh Multispeciality Healthcare Pvt. Ltd; Principal Investigator: Sanjay Kala, GSVM Medical College; Principal Investigator: Vikas Matai, Jupiter Hospital & Research Centre

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2023
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: June 15, 2023
• First Submitted That Met QC Criteria: July 6, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Ulcer; Diabetic Foot; Infections
• Other Study ID Numbers: TP-102_102

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