Study to assess the Safety and Efficacy of Bacteriophage in the treatment of Diabetic foot infection.
Scientific Title of Study
A phase 2b clinical study to evaluate the safety and efficacy of topical administration of Bacteriophage therapy TP-102 in patients with Diabetic foot infection.
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Jayashri Krishnan
Designation
Vice President Operations
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
Tower 2, 1st Floor, South Wing, L & T Business Park, Plot no 12/4, Sector 27 D, Delhi Mathura Road, Near Sarai Khawaja Metro station, Faridabad – 121003, Haryana, India
Faridabad HARYANA 121003 India
Phone
9771407484
Fax
911296613520
Email
jayashri.krishnan@jssresearch.com
Details of Contact Person Scientific Query
Name
Dr Sonika Newar
Designation
General Manager Medical Monitoring and Safety
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
Tower 2 , 1st Floor, South Wing, L & T Business park,
Plot no 12/4, Sector 27 D, Delhi Mathura Road, Near Sarai Khawja Metro station, Faridabad – 121003, India.
Faridabad HARYANA 121003 India
Phone
8800799887
Fax
911296613520
Email
Sonika.newar@jssresearch.com
Details of Contact Person Public Query
Name
Dr Jayashri Krishnan
Designation
Vice President Operations
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
Tower 2, 1st Floor, South Wing, L & T Business Park, Plot no 12/4, Sector 27 D, Delhi Mathura Road, Near Sarai Khawaja Metro station, Faridabad – 121003, Haryana, India
Faridabad HARYANA 121003 India
Phone
09771407484
Fax
911296613520
Email
jayashri.krishnan@jssresearch.com
Source of Monetary or Material Support
TechnoPhage S.A.,
Avenida Prof. Egas Moniz EdifÃcio Egas Moniz,
Piso 2 – Ala A 1649-028 Lisboa, Portugal
Primary Sponsor
Name
TechnoPhage
Address
Avenida Prof. Egas Moniz EdifÃcio Egas Moniz, Piso 2 – Ala A 1649-028 Lisboa, Portugal
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
JSS Medical Research Asia Pacific Private Limited
Tower 2, 1st Floor, South Wing, L&T Business Park, Plot no 12/4, Sector 27 D, Delhi Mathura Road, Faridabad (India) – 121003.
Ground floor, 15, Shashwat, Opp ESI Hospital, Gotri Road, Vadodara - 390021 Vadodara GUJARAT
9904402122
amankhanna1974@gmail.com
Dr Arcojit Ghosh
B P Poddar Hospital & Medical Research Ltd.
Clinical Research Department, 2nd Floor, B P Poddar Hospital and Medical Research Ltd,
71/1, Humayun Kabir Sarani, New Alipore, Block G Kolkata-700053, West Bengal, India.
Kolkata WEST BENGAL
Ground Floor, Principal Office, Department of Surgery, GSVM Medical College, Swaroop Nagar, Kanpur, Uttar Pradesh- 208002 Kanpur Nagar UTTAR PRADESH
9839210012
dr_sanjay_kala@yahoo.com
Dr Vikas Matai
Jupiter Hospital & Research Centre
First floor, OPD No.1, Surgical Department, Jupiter Hospital and Research Centre, Opp. ICAI Bhavan Sun Pharma- Atladra Road, Atladra, Vadodara, Gujarat- 390012 Vadodara GUJARAT
7383073733
drvikasmatainm@gmail.com
Dr G Senthil
M.V Hospital for Diabetes Pvt. Ltd
Ground floor, Chairman room, No: 04 West Madha Church Street, Royapuram, Chennai-600013, TamilNadu, India Chennai TAMIL NADU
9840067251
senaakee@gmail.com
Dr Vivek Agarwal
Maharaja Agrasen Hospital
Room No. 26, 2nd Floor, Old building, Maharaja Agrasen Hospital, Shivaji Park, West Punjabi Bagh, New Delhi-110026 New Delhi DELHI
9999349230
dr.vivekaggarwal@yahoo.com
Dr Parikh Shailesh Niranjan
Parikh Multispeciality Health Care Private Limited
First floor, Consulting room No.1, Surgical
A4 Bhagwati Park, Opposite Tube Company, Near Gajanan Complex, Old Padra Road, Vadodara- 390020 Vadodara GUJARAT
(1) ICD-10 Condition: L975||Non-pressure chronic ulcer of other part of foot,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Bacteriophage TP-102
Topical application of TP-102 at dosage of 1 mL per cm3 of ulcer, TIW, every other day, a total of 12 treatments in 28 days + Standard of Care
Comparator Agent
Normal saline solution, NaCl 0.9 %
Topical application of Normal saline solution (NaCl) 1 mL per cm3 of ulcer, TIW, every other day, a total of 12 treatments in 28 days + Standard of Care.
1. Aged > 18 years old.
2. Established diagnosis of Diabetes mellitus (Type I or Type II)
3. Glycosylated hemoglobin (HbA1C) value < 12.0 %
4. Designated foot infection meets the following criteria-
a. Present for at least 3 weeks
b. Below -ankle, full thickness, cutaneous ulcer.
c. Wound area (after debridement, if applicable) below or equal to 20.0 cm2
d. IWGDF/IDSA classification of Mild to moderate /PEDIS infection grade 2 or 3
e. PEDIS perfusion grade 1 or 2
f. 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)
5. 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-
6. Patients with suitable physical and mental health as determined by the Investigator based on medical history and general physical examination.
7. Patients with childbearing potential must have a negative Serum Pregnancy Test at screening-
8. Female and male participants of reproductive potential who are participating in sexual activity that could lead to pregnancy must agree to use one of the following forms of birth control whilst receiving study medications and for 4 (four) weeks after stopping study medications:
a. Male or female condoms
b. Diaphragm or cervical cap with spermicide (if available)
c. Intrauterine device (IUD)
d. Oral contraceptive or Depo-Provera
Note A: Female participants who are not of reproductive potential are eligible without the use of contraceptives. Participant reported history is acceptable documentation of menopause (i.e., at least one-year amenorrheic), hysterectomy or bilateral oophorectomy or bilateral tubal ligation; these participants are all considered not of reproductive potential.
Note B: Male participants who are not of reproductive potential (i.e., documented azoospermia) or whose female partner/s are not of reproductive potential (as defined above) are eligible without requiring the use of contraceptives.
9. ICF signed voluntarily before any study-related procedure is performed, indicating that the patient understands the purpose and procedures required in the study and is willing to participate.
ExclusionCriteria
Details
1.Infected study ulcer less than 2 cm away from other ulcers, in the case of multiple ulcers.
2. Patient receiving Hyperbaric Oxygen Therapy (HBOT), Negative Pressure Wound Therapy (NPWT), Bioengineering Skin (BES) substitutes and/or growth factors.
3. Presence of active malignant or benign tumors of any kind, (with exception to nonmelanoma skin cancer as per investigator’s discretion);
4. Being pregnant or breastfeeding;
5. 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;
6. 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;
7. Patient which, in the opinion of the investigator, may not comply with study related procedures;
8. Participants with hypersensitivity to any component of investigational products
Method of Generating Random Sequence
Permuted block randomization, fixed
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Treatment emergent Adverse events,
Statistically significant changes in the percentage of patients in the respective IWGDF/IDSA classes ,
Percentage of patients that achieve at least 50% reduction in wound surface area by week 4
Treatment emergent Adverse events,
Statistically significant changes in the percentage of patients in the respective IWGDF/IDSA classes ,
Percentage of patients that achieve at least 50% reduction in wound surface area by week 4
Secondary Outcome
Outcome
TimePoints
1.Change in mean CRP/ESR/PCT/WBC count value
2. Percentage of patients with a value over clinical diagnostic cut-off for DFI for CRP/ESR/PCT/WBC count
3. Percentage eradication of TP-102 susceptible strains for TP-102 versus Placebo
4. Percentage of patients with target strain not susceptible to TP-102 for TP-102 versus Placebo
5. Changes in wound size, depth, granulation, complete or partial closure
6. Percentage of patients that achieve wound healing complete wound closure
Day 1 (Baseline) to EOT
Day 1 (Baseline) to EOT
At End of Treatment
At End of Treatment
Day 3, 8, 15, EOT and EOS
Day 1 (Baseline) to FUP2
Total Sample Size="96" Sample Size from India="64" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase 2b,
double-blinded, randomised, placebo-controlled, multicentre study to determine
the safety and efficacy of TP-102, in patients with DFI.
A minimum of 80 (Eighty) patients (maximum of 96
(Ninety-six)) with an infected DFU and with at least one target bacterial
strain (Pseudomonas aeruginosa, Staphylococcus aureus or Acinetobacter
baumannii) susceptible to TP-102, causing the infection as determined from the
culture taken from the target ulcer at screening visit, will be included within
10 days from screening.
Patients will be randomly
assigned in a 1:1 ratio to one of two treatments arms (TP-102 or Placebo) at
Day 1. The wound SoC procedures are in accordance to each sites normal DFI
routine. 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
(consecutive days of treatment are not allowed) and a maximum of 3 (three) days
without treatment.
After completing treatment, patients will return for
scheduled Follow-Up (FU) visits: 15 (FU1) and 60 (FU2) days after the last IP
administration.
Assessments for efficacy and
safety will include concomitant medications and AEs/AESI/SAE, physical
examination, vital signs, clinical laboratory tests, target ulcer assessment
(size, depth, volume, granulation, IWGDF-ISDA and PEDIS infection
classification and DFUWI score), and wound biopsy (swab only as indicated) to
determine the presence and speciation of bacteria.
As part of the DSMB, a
dedicated, independent Adaptive Committee, exclusive of the SRC, will review
safety data and infectivity scoring and may recommend enrichment of the active
arm where SAEs indicate that Placebo + SoC is significantly failing.
In this phase 2, PoC study, the
primary objectives are to evaluate the safety and efficacy of TP-102 as
measured by TEAEs compared to Placebo and reduction of wound infection
(IWGDF/ISDA and PEDIS infection classification and DFUWI score) and wound
surface by topically applied TP-102 in addition to SoC in DFIs. The reduction
of wound surface will be evaluated as a prognostic indicator of complete wound
healing at 3 months after treatment with IP since wound healing depends on
several factors that go beyond the infection reduction/ eradication.