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Bacteriophage Therapy TP-102 in Diabetic Foot Ulcers (REVERSE)

Primary Purpose

Diabetic Foot Ulcer, Pseudomonas Aeruginosa Infection, Staphylococcus Aureus Infection

Status
Completed
Phase
Phase 1
Locations
Israel
Study Type
Interventional
Intervention
TP-102
Sponsored by
Technophage, SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Foot Ulcer focused on measuring Bacteriophage therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Both cohorts:

  • Type 1 or type 2 diabetes mellitus with glycated hemoglobin (HbA1c) ≤10, 5%
  • Suitable physical and mental health as determined by the investigator based on medical history and general physical examination.
  • Subjects must be medically stable based on clinical laboratory tests, medical history and vital signs. Clinical laboratory tests should be within normal values or not clinically significant, unless directly related to the condition of diabetes.
  • Female subjects must fulfil one of the following criteria:

    1. At least 1 year post-menopausal (amenorrhea >12 months prior to screening);
    2. Surgically sterile (bilateral oophorectomy or hysterectomy);
    3. If of childbearing potential, must agree to use a highly effective method of birth control from screening until 14 days after the last administration of IP.
  • Female subjects of childbearing potential must have a negative pregnancy test at screening.
  • Male subjects with a female partner of child-bearing potential or pregnant partner must agree to use a condom from screening until 14 days after the last IP application.
  • ICF signed voluntarily before any study-related procedure is performed, indicating that the subject understands the purpose of, and procedures required for the study and is willing to participate in the study.

Part A:

- Non-infected diabetic foot ulcer perfusion grade 1, depth grade 1 and infection grade 1 according to PEDIS classification.

Part B

  • Infected diabetic foot ulcer meeting perfusion grade 1 or 2, depth grade 1 or 2 and infection 2 or 3,except if presence of abscess, fasciitis, osteomyelitis, and septic arthritis, according to PEDIS definition.
  • Infected with at least one bacterial strain susceptible to bacteriophage cocktail assessed from culture.

Exclusion Criteria:

Both cohorts:

  • Study ulcer less than 2 cm away from other ulcers in case of multiple ulcers.
  • History in the 5 previous years of any cancer requiring systemic chemotherapy or radiation.
  • A condition that, in the opinion of the Investigator, could compromise the well being of the subject or course of the study, or prevent the subject from meeting or performing any study requirements.
  • Immunocompromised subjects due to illness, organ transplant, or immune suppressive therapies (e.g. oral or parental corticosteroids, methotrexate, immune modulators) 3 months prior to screening. Ad hoc low dose inhaled corticosteroids or topical corticosteroids are not allowed from 2 weeks prior to randomization.
  • 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 or 5 half-lives, whichever is longer.
  • Subjects that, in the opinion of the Investigator or their treating physician, are dependent of the following therapies for their ulcer treatment:

    • Topical antimicrobial treatment (including isobetadine gel/dressing, silver nitrate dressing, topical antibiotic)
    • Enzymatic, autolytic, maggot debridement
    • Any active wound healing products (e.g., Dermagraft, Apligraf, Regranex, or Tegaderm hydrogel or others.)
    • Physical or cleansing modalities, antiseptics, corticosteroids, growth factors, solutions other than sterile normal saline and ulcer treatments.

Part A:

- Clinically infected ulcers

Part B:

  • Suspected or confirmed abscess, fasciitis, osteomyelitis or septic arthritis.
  • Subjects meeting grade 3 or above PEDIS perfusion criteria
  • Planed or anticipated surgery after screening

Sites / Locations

  • Hadassah Medical Center, Ein Kerem
  • Tel Aviv Sourasky Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part A- Cohort 1

Part B- Cohort 2

Arm Description

8 eligible subjects with non-infected DFU will be enrolled (Cohort 1) and receive IP three times weekly (TIW) every other day for up to one week. Of these 8 enrolled subjects, 6 subjects will be randomized to TP-102 and 2 to placebo. Subjects will be followed-up for 7 days.

18 subjects with a DFU with a grade 2 or 3 infection, as per PEDIS classification, and at least one bacterial strain susceptible to bacteriophage cocktail will be included in Cohort 2. Subjects will receive IP TIW, every other day, up to four weeks and will be randomized at a 2:1 randomization rate to either: TP-102 q.d 3x weekly up to four weeks (n=12) Placebo q.d. 3x weekly up to four weeks (n=6) Subjects will be followed-up for 7 days.

Outcomes

Primary Outcome Measures

1. Incidence and severity of treatment-emergent solicited local and systemic AEs and relationship to IP from first administration until 1 week after end of treatment (EOT) (end of study -EOS)
Local AEs include erythema/redness, swelling/induration, pain and tenderness Systemic AEs include fatigue, myalgia, fever, headache and gastrointestinal symptoms (nausea, vomiting, diarrhea)
2. Incidence and severity of treatment-emergent unsolicited AEs and relationship to IP from first administration until EOS.
3. Incidence and severity of treatment-emergent SAEs and relationship to IP from first administration until EOS.

Secondary Outcome Measures

Proportion of subjects with significant reduction or eradication from baseline in microbiologic data via culture (cfu) at d3, d8, d15, d22, d26 and EOS
Time (days) to significant reduction or eradication of target bacteria via culture.
Changes in wound/ulcer healing from to baseline in terms of wound size and depth (cm^3) at EOT.
Changes in wound/ulcer healing from to baseline in terms of wound complete closure and partial closure (25%, 50% and 75%) at EOT.

Full Information

First Posted
March 2, 2021
Last Updated
October 3, 2022
Sponsor
Technophage, SA
Collaborators
VectorB2B
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1. Study Identification

Unique Protocol Identification Number
NCT04803708
Brief Title
Bacteriophage Therapy TP-102 in Diabetic Foot Ulcers
Acronym
REVERSE
Official Title
A Double-Blind and Randomized Study to Determine the Safety and Tolerability of Multiple Doses of TP-102 in Subjects With Non-Infected and Infected Diabetic Foot Ulcers
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
March 22, 2021 (Actual)
Primary Completion Date
August 7, 2022 (Actual)
Study Completion Date
September 5, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Technophage, SA
Collaborators
VectorB2B

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase I/IIa trial designed to evaluate topical bacteriophage therapy in patients with diabetic foot ulcers.
Detailed Description
The primary objective of this study is to evaluate the safety of a topical bacteriophage cocktail in the treatment of non infected and infected diabetic foot ulcers with Pseudomonas aeruginosa, Staphylococcus aureus and/or Acinetobacter baumanni. Patients will also be evaluated for bacterial clearance and wound reduction.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Foot Ulcer, Pseudomonas Aeruginosa Infection, Staphylococcus Aureus Infection, Acinetobacter Infection
Keywords
Bacteriophage therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A- Cohort 1
Arm Type
Experimental
Arm Description
8 eligible subjects with non-infected DFU will be enrolled (Cohort 1) and receive IP three times weekly (TIW) every other day for up to one week. Of these 8 enrolled subjects, 6 subjects will be randomized to TP-102 and 2 to placebo. Subjects will be followed-up for 7 days.
Arm Title
Part B- Cohort 2
Arm Type
Experimental
Arm Description
18 subjects with a DFU with a grade 2 or 3 infection, as per PEDIS classification, and at least one bacterial strain susceptible to bacteriophage cocktail will be included in Cohort 2. Subjects will receive IP TIW, every other day, up to four weeks and will be randomized at a 2:1 randomization rate to either: TP-102 q.d 3x weekly up to four weeks (n=12) Placebo q.d. 3x weekly up to four weeks (n=6) Subjects will be followed-up for 7 days.
Intervention Type
Biological
Intervention Name(s)
TP-102
Intervention Description
One mL of IP solution will be applied topically per cm3 of target ulcer. The titer of each bacteriophage in TP 102 is 1x10^9 plaque forming units per milliliter (PFU/mL).
Primary Outcome Measure Information:
Title
1. Incidence and severity of treatment-emergent solicited local and systemic AEs and relationship to IP from first administration until 1 week after end of treatment (EOT) (end of study -EOS)
Description
Local AEs include erythema/redness, swelling/induration, pain and tenderness Systemic AEs include fatigue, myalgia, fever, headache and gastrointestinal symptoms (nausea, vomiting, diarrhea)
Time Frame
1 week
Title
2. Incidence and severity of treatment-emergent unsolicited AEs and relationship to IP from first administration until EOS.
Time Frame
1 week
Title
3. Incidence and severity of treatment-emergent SAEs and relationship to IP from first administration until EOS.
Time Frame
1 week
Secondary Outcome Measure Information:
Title
Proportion of subjects with significant reduction or eradication from baseline in microbiologic data via culture (cfu) at d3, d8, d15, d22, d26 and EOS
Time Frame
35 days
Title
Time (days) to significant reduction or eradication of target bacteria via culture.
Time Frame
35 days
Title
Changes in wound/ulcer healing from to baseline in terms of wound size and depth (cm^3) at EOT.
Time Frame
35 days
Title
Changes in wound/ulcer healing from to baseline in terms of wound complete closure and partial closure (25%, 50% and 75%) at EOT.
Time Frame
35 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Both cohorts: Type 1 or type 2 diabetes mellitus with glycated hemoglobin (HbA1c) ≤10, 5% Suitable physical and mental health as determined by the investigator based on medical history and general physical examination. Subjects must be medically stable based on clinical laboratory tests, medical history and vital signs. Clinical laboratory tests should be within normal values or not clinically significant, unless directly related to the condition of diabetes. Female subjects must fulfil one of the following criteria: At least 1 year post-menopausal (amenorrhea >12 months prior to screening); Surgically sterile (bilateral oophorectomy or hysterectomy); If of childbearing potential, must agree to use a highly effective method of birth control from screening until 14 days after the last administration of IP. Female subjects of childbearing potential must have a negative pregnancy test at screening. Male subjects with a female partner of child-bearing potential or pregnant partner must agree to use a condom from screening until 14 days after the last IP application. ICF signed voluntarily before any study-related procedure is performed, indicating that the subject understands the purpose of, and procedures required for the study and is willing to participate in the study. Part A: - Non-infected diabetic foot ulcer perfusion grade 1, depth grade 1 and infection grade 1 according to PEDIS classification. Part B Infected diabetic foot ulcer meeting perfusion grade 1 or 2, depth grade 1 or 2 and infection 2 or 3,except if presence of abscess, fasciitis, osteomyelitis, and septic arthritis, according to PEDIS definition. Infected with at least one bacterial strain susceptible to bacteriophage cocktail assessed from culture. Exclusion Criteria: Both cohorts: Study ulcer less than 2 cm away from other ulcers in case of multiple ulcers. History in the 5 previous years of any cancer requiring systemic chemotherapy or radiation. A condition that, in the opinion of the Investigator, could compromise the well being of the subject or course of the study, or prevent the subject from meeting or performing any study requirements. Immunocompromised subjects due to illness, organ transplant, or immune suppressive therapies (e.g. oral or parental corticosteroids, methotrexate, immune modulators) 3 months prior to screening. Ad hoc low dose inhaled corticosteroids or topical corticosteroids are not allowed from 2 weeks prior to randomization. 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 or 5 half-lives, whichever is longer. Subjects that, in the opinion of the Investigator or their treating physician, are dependent of the following therapies for their ulcer treatment: Topical antimicrobial treatment (including isobetadine gel/dressing, silver nitrate dressing, topical antibiotic) Enzymatic, autolytic, maggot debridement Any active wound healing products (e.g., Dermagraft, Apligraf, Regranex, or Tegaderm hydrogel or others.) Physical or cleansing modalities, antiseptics, corticosteroids, growth factors, solutions other than sterile normal saline and ulcer treatments. Part A: - Clinically infected ulcers Part B: Suspected or confirmed abscess, fasciitis, osteomyelitis or septic arthritis. Subjects meeting grade 3 or above PEDIS perfusion criteria Planed or anticipated surgery after screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ran Nir-Paz, MD
Organizational Affiliation
Hadassah Medical Organization
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ronen Ben Ami, MD
Organizational Affiliation
Tel-Aviv Sourasky Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hadassah Medical Center, Ein Kerem
City
Jerusalem
ZIP/Postal Code
91091
Country
Israel
Facility Name
Tel Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Bacteriophage Therapy TP-102 in Diabetic Foot Ulcers

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