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

• ClinicalTrials.gov Identifier: NCT05948592
• Recruitment Status: Recruiting
• First Posted: July 17, 2023
• Last Update Posted: April 11, 2024
• Sponsor: Technophage, SA
• Collaborator: VectorB2B
• Information provided by (Responsible Party): Technophage, SA

Tracking Information

• First Submitted Date: June 15, 2023
• First Posted Date: July 17, 2023
• Last Update Posted Date: April 11, 2024
• Actual Study Start Date: November 8, 2023
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 6, 2023)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 6, 2023)

• 1. Change in mean CRP/ESR/PCT/WCC value for TP-102 versus Placebo [ Time Frame: 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 [ Time Frame: Baseline to EOT, , aproximately 12 weeks ]
• 3. Percentage eradication of TP-102 susceptible strains for TP-102 versus Placebo at EOT; [ Time Frame: EOT, , aproximately 12 weeks ]
• 4. Percentage of patients with target strain not-susceptible to TP-102 for TP-102 versus Placebo at EOT; [ Time Frame: EOT, , aproximately 12 weeks ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Bacteriophage Therapy TP-102 in Patients With Diabetic Foot Infection
• Official Title: A Phase 2 CT to Evaluate the Safety and Efficacy of Topical Administration of Bacteriophage Therapy TP-102 in Patients With DFI
• Brief Summary: 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)).

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diabetic Foot Infection

Intervention

• 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).
• 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).

Study Arms

• 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.
  Intervention: Biological: TP-102
• 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.
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 6, 2023): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 31, 2024
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sofia Corte Real; +351215943993; scortereal@technophage.pt

Contact: Margarida Barreto; mbarreto@technophage.pt

• Listed Location Countries: India, United States

Administrative Information

• NCT Number: NCT05948592
• Other Study ID Numbers: TP-102_102
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Technophage, SA
• Original Responsible Party: Same as current
• Current Study Sponsor: Technophage, SA
• Original Study Sponsor: Same as current
• 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

• PRS Account: Technophage, SA
• Verification Date: April 2024