Bacteriophage Therapy TP-102 in Patients With Diabetic Foot Infection

Diabetic Foot Infection Clinical Trial

— REVERSE2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05948592
• Other study ID #: TP-102_102
• Status: Recruiting
• Phase: Phase 2
• Start date: November 8, 2023
• Est. completion date: July 31, 2024

Study information

• Verified date: April 2024
• Source: Technophage, SA
• Contact: Sofia Corte Real
• Phone: +351215943993
• Email: scortereal[@]technophage.pt
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: July 31, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetic Foot
• Diabetic Foot Infection
• Infections

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).

Locations

Country	Name	City	State
India	MV Hospital for Diabetes Pvt. Ltd	Chennai
India	GSVM Medical College	Kanpur
India	Crescent Hospital & Heart Centre	Nagpur
India	Shree Siddhi Vinayak Hospital	Nashik
India	Aman Hospital & Research Centre	Vadodara
India	Jupiter Hospital & Research Center	Vadodara
India	Parikh Multispeciality Healthcare Pvt. Ltd	Vadodara
India	Yalamanchi Hospitals & Research Centers Pvt. Ltd	Vijayawada
United States	VA Greater LA Healthcare System	Los Angeles	California
United States	Keralty Hospital Miami	Miami	Florida
United States	ILD Research Center	Vista	California

Sponsors (2)

Lead Sponsor	Collaborator
Technophage, SA	VectorB2B

Countries where clinical trial is conducted

United States,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1. Number and percentage of treatment emergent adverse events (TEAEs)	See above	From baseline to EOT, aproximately 12 weeks
Primary	2. Mean DFUWI score (total AUC) for TP-102 versus Placebo	See above	From baseline to EOT, , aproximately 12 weeks
Primary	3. Percentage of patients that achieve a 50% reduction in wound surface area by week 4		Week 4
Secondary	1. Change in mean CRP/ESR/PCT/WCC value for TP-102 versus Placebo		From baseline to EOT, , aproximately 12 weeks
Secondary	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
Secondary	3. Percentage eradication of TP-102 susceptible strains for TP-102 versus Placebo at EOT;		EOT, , aproximately 12 weeks
Secondary	4. Percentage of patients with target strain not-susceptible to TP-102 for TP-102 versus Placebo at EOT;		EOT, , aproximately 12 weeks