Clinical Trial to Demonstrate the Safety and Efficacy of DUOFAG®

A Prospective, Randomized, Double-blind, Placebo-controlled Phase I/IIa Clinical Trial to Demonstrate the Safety and Efficacy of DUOFAG® in Bacterial Infection Treatment in Patients With Surgical Wounds

DUOFAG® is a phage cocktail containing bacteriophages active against Staphylococcus aureus and Pseudomonas aeruginosa. It is an investigational medicinal product for the treatment of surgical site infections caused by S. aureus and P. aeruginosa.

The primary objective of the study is to demonstrate the safety of DUOFAG® and the clinical and microbiological change within 10 weeks after the start of treatment or until healing.

Study Overview

• Status: Recruiting
• Conditions: Bacterial Infections; Surgical Wound Infection; Surgical Site Infection; Staphylococcus Aureus Infection; Pseudomonas Aeruginosa Infection
• Intervention / Treatment: Drug: IMP; Drug: Placebo

Detailed Description

The study population will be recruited in two cohorts. The microbiological population of the wound will be evaluated to analyze the effect of the treatment. If the safety profile and treatment effect are going to be satisfactory, the recruitment will proceed with Cohort 2.

In both cohorts, the Investigational Medicinal Product (IMP) or placebo (the randomization ratio will be 1:1) will be applied twice a day for two weeks or until the commencement of healing.

Patients will receive the standard of care during the whole study duration. No concomitant treatment is planned during the treatment period.

The Adverse Events will be recorded on basis of an open interview without soliciting questions, and clinical observation. In case of occurrence of an adverse event (AE) with moderate or severe intensity possibly related to IMP, the treatment will be stopped, and the AE will be followed up until resolution.

Adverse Event descriptions, their severity (mild, moderate, or severe), duration and their perceived relationship to the study medication (probable, possible, unlikely, not related, and not sure) will be recorded.

The mLUMT (modified Leg Ulcer Measurement Tool) total score and individual item scores change since the baseline visit will be recorded.

Time from the start of the study treatment until the bacterial infection eradication - i. e. the swab sample is negative on S. aureus and/or P. aeruginosa will be recorded.

Time from the start of the study treatment until the wound is closed/healed (as assessed by investigator) will be recorded.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Dana Štveráková, Ph.D.; Phone Number: +420 604 912 940; Email: stverakova@mbph.cz
• Study Contact Backup: Name: Monika Peichlová, Ing.; Phone Number: +420 777 487 400; Email: peichlova@mbph.cz

Study Locations

• Czechia
  • Czech Republic
    • Brno, Czech Republic, Czechia, 602 00
      • Recruiting
      • St. Anne's University Hospital Brno
      • Contact: Dominik Maduda, MUDr.; Phone Number: +420 543 182 432; Email: dominik.maduda@fnusa.cz
      • Contact: Kateřina Bílá, MUDr.; Phone Number: +420 543 182 451; Email: katerina.bila@fnusa.cz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with surgical wound infection and/or dehiscence
• Wound infected by S. aureus and/or P. aeruginosa according to wound swab.
• Wound in the groin or any other skin fold as per Investigator's discretion.
• Signed Informed Consent Form, approved by the ethical committee and competent authority.
• The age between 18 and 75 years.
• Patients able and willing to comply with study procedures.
• There are no contraindications for planned concomitant medication.
• Persisting symptoms of bacterial infection < 3 weeks since the surgery.
• Women of childbearing potential must take highly effective contraceptive measures since the study start and one month after the treatment administration at a minimum.

Exclusion Criteria:

• History of an organ or bone marrow transplantation.
• Any autoimmune disease.
• Uncompensated diabetes mellitus, confirmed by the concentration of HbA1c >60 mmol/mol (6%).
• Systematic immunosuppressive therapy.
• Malignancy treatment <1 year before the Baseline visit.
• COVID-19 infection <3 months before the Baseline visit, any signs of post-COVID syndrome.
• Pregnancy or planning to become pregnant during the study.
• Breastfeeding.
• Participation in another clinical study.
• Hypersensitivity to the IMP or placebo.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational arm; DUOFAG® (the investigational medicinal product - IMP) will be administered twice a day for two weeks. DUOFAG® will be sprayed on the surgical wound. The phage titers of each bacteriophage in DUOFAG® is ≥ 10 000 000 PFU/mL (PFU = plaque forming units).	Drug: IMP; DUOFAG® is a phage cocktail (cutaneous liquid) manufactured by MB PHARMA s.r.o. and it contains bacteriophages active against Staphylococcus aureus and Pseudomonas aeruginosa.; Other Names: DUOFAG®
Placebo Comparator: Control arm; Placebo (physiological saline solution - 0.9% sodium chloride solution) will be administered twice a day for two weeks. Placebo will be sprayed on the surgical wound.	Drug: Placebo; 0.9% Sodium Chloride Injection solution was manufactured by B. Braun Melsungen AG. Marketing authorization number assigned from the State Institute for drug control (Czech Republic): 76/847/92-B/C; Other Names: 0.9% Sodium Chloride Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary endpoint - Cohort 1	The endpoint will be the frequency of all (local and systemic) reactions with suspected or confirmed relation to IMP.	10 weeks (the maximum duration)
Primary endpoint - pooled Cohorts 1 & 2	Time to commencement of healing.	10 weeks (the maximum duration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoints (assessed in pooled Cohorts 1 & 2)	The frequency of the following symptoms following the IMP application will be evaluated: local reactions, systemic reactions.	10 weeks (the maximum duration)
Microbiological endpoints (assessed in pooled Cohort 1 and Cohort 2)	Change of the microbiological profile of the wound assessed by swab.	2 weeks (the maximum duration)
Clinical efficacy endpoints	The mLUMT total score change since Baseline, time since the start of the study treatment until the bacterial infection eradication, time since the start of the study treatment until the granulation process in the wound has started, time since the start of the study treatment until the wound is closed as assessed by Investigator.	10 weeks (the maximum duration)

Collaborators and Investigators

• Sponsor: MB PHARMA s.r.o.
• Investigators: Principal Investigator: Robert Staffa, prof., St. Anne's University Hospital Brno

Publications and helpful links

Helpful Links

• MB PHARMA website

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Staphylococcus aureus; Bacterial infections; Pseudomonas aeruginosa; Surgical site infection; Bacteriophage; Phage Therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Wounds and Injuries; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Surgical Wound; Surgical Wound Infection; Wound Infection; Bacterial Infections; Staphylococcal Infections; Pseudomonas Infections
• Other Study ID Numbers: DUO2022_01; 2022-002412-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No