PhagoDAIR I : A Pilot, Multicenter, Randomized, Non Comparative, Double-Blind Study of Phage Therapy in Patients with Hip or Knee Prosthetic Joint Infection due to Staphylococcus aureus Treated with DAIR and Antibiotic Therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Phaxiam Therapeutics

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

15 Jun 2022 → 8 Apr 2025

Decision date (initial)

2024-08-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516207-17-00

EudraCT number

2021-004469-11

ClinicalTrials.gov

NCT05369104

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacokinetic

To estimate the rate of clinical control of infection due to Staphylococcus aureus of two different therapeutic regimens: DAIR + curative antibiotics therapy combined with bacteriophages or solution of NaCl 0.9%; in patients presenting a Prosthesis Joint Infection (PJI) later than 1 month after the arthroplasty, with the indication of DAIR + Suppressive Antibiotics Therapy (SAT) which will allow to calculate the sample size for future comparative studies.

Secondary objectives 9

1. To assess the safety of two different therapeutic regimens (DAIR + curative antibiotics therapy combined with bacteriophages or Solution of NaCl 0.9%) during the whole study
2. To describe initial activity of phages on patients’ Staphylococcus aureus strain and the clinical outcome (infection control or relapse) of patients.
3. To describe superinfected patients (other species found in per operative sample) in terms of clinical control of the infection
4. To describe the profile of the Staphylococcus aureus strain in case of failure
5. To describe the hospitalization duration
6. To describe the quality of life for patients at each visit
7. To describe the rehabilitation
8. To estimate the rate of clinical control of infection due to Staphylococcus aureus of two different therapeutic regimens (DAIR + curative antibiotics therapy combined with bacteriophages or solution of NaCl 0.9%)
9. To estimate the rate of clinical control of infection due to Staphylococcus aureus after rescue treatment and to assess the safety of rescue treatment in patients with relapse due to Staphylococcus aureus and to describe characteristic of the product.

Conditions and MedDRA coding

knee or hip prosthetic joint infection (PJI) due to Staphylococcus aureus, with the indication of DAIR and Suppressive Antibiotics Therapy (SAT)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Male or female ≥ 18 years
2. Staphylococcus aureus monomicrobial knee or hip PJI > 1 month after prosthesis implantation with clinical signs of infection and with indication of DAIR with direct closure (if associated flap, arthrotomy must be sealed), and Suppressive Antibiotics Therapy (SAT)
3. Staphylococcus aureus only in joint fluid within 6 months before randomization or in case of relapse of infection under antibiotics therapy after a DAIR performed within 6 months before pre-inclusion visit
4. Without preoperative diagnosis of superinfection due to another pathogen if treatment is administered at the end of the DAIR
5. Without diagnosis of superinfection due to another pathogen identified within 72h after a bacteriological sample performed during a DAIR if treatment is administered 14±2 days after a DAIR.
6. Displaying the susceptibility of the strain to at least one of the phages.
7. Patient with a life expectancy of 2 years and more as determined by the principal investigator
8. Females of childbearing potential/Sexually active males with partner of childbearing potential: commitment to consistently and correctly use an acceptable effective method of birth control (oral, transdermal, systemic or implant contraception birth control, intrauterine devices, condom) for 1 month after the last study drug administration
9. Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhea duration at least 12 months)
10. Negative pregnancy test
11. Signing a written informed consent before any study related procedures
12. Affiliated to a national social security system and / or private health insurance in compliance with the recommendations of National Law in force relating to biomedical research

Exclusion criteria 17

1. Early Staphylococcus aureus Prosthesis Joint infection ( < 1 month after the prosthesis implantation)
2. Other germ found in culture of joint fluid sample
3. Displaying no susceptibility of the strain to anti-Staphylococcus aureus bacteriophages
4. Patients with ASA score ≥ 4
5. Severe sepsis or Septic shock or hemodynamic instability
6. Patients with an indication to prosthesis replacement or amputation
7. Immunosuppressed patients
8. Known allergic reactions to components of phages products
9. Relapse between DAIR and treatment administration planned 14±2 days after a DAIR
10. Medical history which in the opinion of the investigator would mean that the patient is unsuitable for participation in the study
11. Patient who, in the judgment of the Investigator, is likely to be noncompliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development
12. Currently in exclusion period from a previous study
13. Concomitant participation to another interventional clinical trial or previous participation with active drug levels still present, i.e. the last medication intake is less than 4 half-lives ago
14. Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the treatment period and up to 1 month after the last administration of study drug
15. Women/Men refusing to use an acceptable effective contraception during 1 month after the last administration of study drug
16. No possibility of contact in case of emergency
17. Minors, persons deprived of liberty by judicial or administrative decision, persons receiving psychiatric care and persons admitted to a health or social institution, to adult patient under legal protection or unable to express consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Clinical control of infection defined by: no clinical signs of evolutive infection: no fever (defined by a temperature less than 38°C) due to prosthesis infection and no recurrence, neither recurrent, nor worsening pain
2. Peri articular Inflammatory and infectious Clinical signs will be collected : No local post surgical recurrence or worsening of local articular swelling / No unusual aspect of scar as erythema or abnormal flow or a fistula or inflammatory or local necrosis or no healing
3. No new surgical procedure requested and no Staphylococcus aureus detected

Secondary endpoints 10

1. Safety parameters: adverse events, physical examination, biological tests as hematology and biochemistry during the whole study
2. Initial activity of phages: active bacteriophages (PP1493 and/or PP1815) in regard of the clinical outcome (infection control or relapse) of patients
3. Clinical control of the infection (as described in primary endpoint) for superinfected patients (other species isolated during the surgical procedure)
4. In case of failure, aspiration of joint fluid at time of failure for microbiological test and identification of Staphylococcus aureus strain: antibiogram
5. Duration of hospitalization
6. Questionnaire EQ-5D-5L for quality of life at each visit (except D14±1 and D28±2)
7. Evaluation of joint function with: - Knee: KOOS 12-Knee Survey - Hip: HOOS 12-Hip Survey
8. Clinical control of the infection (as described in primary endpoint)
9. To check potential appearance of abnormal loosening (border with shifting of the prosthesis) or an abnormal periprosthetic border
10. In case of rescue treatment: clinical infection control after the first ultra guided injection, safety parameters, pharmacokinetics, bacteriological and immunological tests

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Phaxiam Therapeutics

Sponsor organisation

Phaxiam Therapeutics

Address

Batiment Bioserra, 60 Avenue Rockefeller 60 Avenue Rockefeller

City

Lyon

Postcode

69008

Country

France

Scientific contact point

Organisation

Phaxiam Therapeutics

Contact name

Dr Pascal Birman

Public contact point

Organisation

Phaxiam Therapeutics

Contact name

Dr Pascal Birman

Third parties 3

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications