Proof of Concept Study to Assess Safety and Efficacy of Phage Therapy in Hip or Knee Prosthetic Joint Infections Due to Staphylococcus Aureus Treated by DAIR. (GLORIA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Phagenix

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Decision date (initial)

2025-03-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

PHAXIAM Therapeutics

External identifiers

EU CT number

2024-516555-40-00

ClinicalTrials.gov

NCT06605651

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the safety and efficacy of phage therapy + DAIR compared with placebo + DAIR up to 3 months

Secondary objectives 10

1. To assess the specific effect on S. aureus infection of phage therapy, + DAIR compared with placebo + DAIR up to 3 months and 12 months
2. To assess the safety of phage therapy + DAIR compared with placebo + DAIR up to 12 months
3. To assess the efficacy of phage therapy + DAIR compared with placebo + DAIR up to 12 months
4. To describe the immunological response in [redacted] and in [redacted] up to 3 months
5. To describe the S. aureus bacterial load (bacteriology) in the [redacted] up to [redacted]
6. To describe Cytology in the [redacted] up to [redacted]
7. To describe the hospitalization duration up to 3 months and up to 12 months
8. To describe the quality of life for patients up to 3 months and up to 12 months
9. To describe joint function rehabilitation up to 3 months and up to 12 months
10. To describe the evolution of X Ray image up to 3 months and up to 12 months

Conditions and MedDRA coding

Hip or Knee prosthetic joint infection due to Staphylococcus aureus

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Male or female ≥ 18 years
2. Knee or Hip PJI according to EBJIS or ICM guidelines (Appendix 6 of protocol)
3. Monobacterial Infection due to S. aureus
4. Without preoperative diagnosis of superinfection due to another pathogen if treatment is administered [redacted] the DAIR (presence of a contaminant is not considered clinically relevant)
5. Without diagnosis of superinfection due to another pathogen identified within 72h after bacteriological sample performed [redacted] DAIR if treatment is administered [redacted] the DAIR
6. Indication for Open DAIR decided by the Multidisciplinary Team and/or Principal Investigator
7. S. aureus in [redacted] during the pre-inclusion period or in case of relapse of infection under antibiotics therapy in the last 6 months before inclusion
8. Patient with a life expectancy of 1 year and more as determined by the principal investigator.
9. 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 until 1 month after the last study drug administration. These include, but not limited to: a.Combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, or transdermal), b.Progestogen-only hormonal contraception (oral, injectable, or implantable), c.Intrauterine device, Intrauterine hormone-releasing system, d.Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. e.For non-vasectomized men having a female partner of childbearing potential, men must agree to use condom until 30 days after the last administration of the study drug.
10. Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhea duration at least 12 months)
11. Negative pregnancy test for women of childbearing potential
12. Signing a written informed consent before any study related procedures including [redacted]
13. 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 18

1. Relapse between DAIR and study drug administration [redacted].
2. Patients who have two planned DAIR in sequence (double DAIR)
3. Patients with ASA score ≥ 4
4. Severe sepsis or Septic shock or hemodynamic instability
5. Patients with an indication for prosthesis exchange, or for joint fusion or for amputation
6. Indication for suppressive antibiotherapy
7. Immunosuppressed patients: Patients having a weakened immune system due to diseases conditions (i.e genetic disorders, malnutrition) or treatment (i.e anticancer drugs or organ transplant)
8. Positive HIV test or active hepatitis B and C
9. Previous treatment by bacteriophages
10. Any known phage allergy and/or to its excipients
11. Elevated ALT or AST above 4 times ULN
12. Medical history which in the opinion of the investigator would mean that the patient is unsuitable for participation in the study.
13. Patient who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development.
14. Currently in exclusion period from a previous study
15. Participate or plan to receive any other investigational drug or therapy or vaccine during the study period.
16. Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the treatment period or 1 month after the last administration of study drug.
17. Women/Men refusing to use an acceptable effective contraception until 1 month after the last administration of study drug.
18. 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 2

1. Incidence of serious adverse events up to 3 months
2. Percentage of Patients with clinical cure up to 3 months

Secondary endpoints 10

1. Percentage of patients with clinical cure from S.aureus infection up to 3 months and 12 months. Percentage of patients with relapse exclusively due to another germ than Staphylococcus aureus up to 3 month and 12 months
2. Incidence of all adverse events and assessment of all safety parameters (Vital signs, ECG/ Echocardiography, hematology, hemostasis and biochemistry) up to 3 months and up to 12 months
3. Percentage of Patient with clinical cure of PJI and up to 12 months.
4. Titration of anti-S. aureus phage antibodies: -In [redacted] at [redacted] in case of relapse and at Early End Visit if it’s occurred before [redacted] for all patients. -In [redacted] at [redacted] in case of relapse if it’s occurred before [redacted] (all patient) and only for knee PJI patients at [redacted].
5. Quantitative or Semi-Quantitative Analysis of bacterial load at [redacted] (all patient) and only for knee PJI patient at [redacted].
6. Quantification and identification of polynuclear of [redacted] at [redacted] (all patients) and [redacted] (only knee PJI).
7. Number and Duration of hospitalization up to 3 months and up to 12 months
8. Quality-of-life questionnaires [redacted] at [redacted].
9. [redacted] Questionnaires at [redacted].
10. X Ray during [redacted] period and at [redacted] to check potential appearance of abnormal loosening (border with shifting of the prosthesis), periprosthetic border.

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Phagenix

Sponsor organisation

Phagenix

Address

60 Avenue Rockefeller

City

Lyon

Postcode

69008

Country

France

Scientific contact point

Organisation

Phagenix

Contact name

Chief Medical Officer

Public contact point

Organisation

Phagenix

Contact name

Chief Medical Officer

Third parties 4

Locations

3 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Results and documents

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

Documents 14 files

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

Application history

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