Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04803708
Recruitment Status : Recruiting
First Posted : March 18, 2021
Last Update Posted : March 18, 2021
Sponsor:
Collaborator:
VectorB2B
Information provided by (Responsible Party):
Technophage, SA

Brief Summary:
This is a Phase I/IIa trial designed to evaluate topical bacteriophage therapy in patients with diabetic foot ulcers.

Condition or disease Intervention/treatment Phase
Diabetic Foot Ulcer Pseudomonas Aeruginosa Infection Staphylococcus Aureus Infection Acinetobacter Infection Biological: TP-102 Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : March 16, 2021
Estimated Primary Completion Date : October 30, 2021
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A- Cohort 1
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.
Biological: TP-102
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).

Experimental: Part B- Cohort 2

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.

Biological: TP-102
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 Measures :
  1. 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) [ Time Frame: 1 week ]
    Local AEs include erythema/redness, swelling/induration, pain and tenderness Systemic AEs include fatigue, myalgia, fever, headache and gastrointestinal symptoms (nausea, vomiting, diarrhea)

  2. 2. Incidence and severity of treatment-emergent unsolicited AEs and relationship to IP from first administration until EOS. [ Time Frame: 1 week ]
  3. 3. Incidence and severity of treatment-emergent SAEs and relationship to IP from first administration until EOS. [ Time Frame: 1 week ]

Secondary Outcome Measures :
  1. 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 ]
  2. Time (days) to significant reduction or eradication of target bacteria via culture. [ Time Frame: 35 days ]
  3. Changes in wound/ulcer healing from to baseline in terms of wound size and depth (cm^3) at EOT. [ Time Frame: 35 days ]
  4. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04803708


Contacts
Layout table for location contacts
Contact: Susana Gonçalves, PharmD 351 217999472 sgoncalves@technophage.pt

Locations
Layout table for location information
Israel
Hadassah Medical Center, Ein Kerem Recruiting
Jerusalem, Israel, 91091
Contact: Ran Nir-Paz, MD    00 972 58 7874044    nirpaz@hadassah.org.il   
Sponsors and Collaborators
Technophage, SA
VectorB2B
Investigators
Layout table for investigator information
Principal Investigator: Ran Nir-Paz, MD Hadassah Medical Center
Layout table for additonal information
Responsible Party: Technophage, SA
ClinicalTrials.gov Identifier: NCT04803708    
Other Study ID Numbers: TP-102_101
First Posted: March 18, 2021    Key Record Dates
Last Update Posted: March 18, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Technophage, SA:
Bacteriophage therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Pseudomonas Infections
Staphylococcal Infections
Acinetobacter Infections
Diabetic Foot
Foot Ulcer
Ulcer
Pathologic Processes
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Leg Ulcer
Skin Ulcer
Skin Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Diabetic Neuropathies
Foot Diseases
Gram-Negative Bacterial Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Moraxellaceae Infections