Evaluation of Autovaccines Versus Antibiotic Regimen in Managing Hip or Knee Prosthesis Infections

The primary objective of this study is to evaluate the clinical relevance of **autovaccines** administered through the sublingual mucosa in patients with joint prosthesis infection, specifically focusing on their ability to decrease clinical symptoms and/or progression of infection. This is clinically significant as it explores a potential alternative to traditional suppressive antibiotic treatments, which may offer benefits in terms of reducing antibiotic resistance and improving patient outcomes in non-curative treatment scenarios.

Secondary objectives include:

• Comparing the efficacy of autovaccines against traditional antibiotic suppressive (TAS) treatment in joint prosthesis infections with a non-curative treatment intention.
• Evaluating patient satisfaction and tolerance to treatment with oral autovaccines.
• Comparing the side effects of autovaccines versus TAS.
• Studying the impact of different non-curative surgical approaches performed prior to adjuvant medical treatment with autovaccines versus TAS.

The clinical trial involves **patients with hip or knee infections**, specifically those with joint prosthesis infections. The study population includes both male and female participants over the age of 18, who are carriers of hip or knee prostheses and have been diagnosed with an active infection. These participants are unable to undergo curative treatment and have provided informed consent to participate in the study. The trial does not include a vulnerable population, and the infections are monomicrobial in nature. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the efficacy of treatment with mucosal bacterial vaccines (autovaccines) versus suppressive antibiotic treatment in subjects with hip or knee prosthesis infections. This study is a **randomized**, **double-blind**, and **controlled** trial, categorized as a low-intervention Phase III study. The trial is expected to span approximately two years, with an estimated recruitment start date of February 16, 2024, and an estimated end date of February 16, 2026. Participants will be involved in the study for a maximum treatment period of 12 months, depending on the specific treatment arm they are assigned to.

The sequence of study visits includes an initial inclusion (screening) visit, where eligibility criteria are assessed. Key inclusion criteria are patients over 18 years of age, carriers of hip or knee prosthesis with an active infection, and those without the possibility of curative treatment. Participants must also provide informed consent and have monomicrobial infections. Following the screening, participants will be randomized into either the autovaccine or antibiotic treatment group. Regular follow-up visits will be conducted to monitor the clinical course, including the presence of exudate, redness of the wound, pain, or other clinical signs of infection. Safety assessments will also be performed to evaluate local and systemic adverse events. The end-of-study visit will conclude the participant's involvement, where final assessments will be made to determine the efficacy and safety of the treatment.

Participants may be withdrawn from the study early if they experience significant adverse events, if they withdraw consent, or if they do not comply with the study protocol. The trial aims to provide evidence-based insights into the clinical relevance of autovaccines administered through the sublingual mucosa in decreasing clinical symptoms and/or progression of infection in patients with joint prosthesis infections.

The clinical trial involves the administration of several **experimental medications** and a non-experimental treatment. The experimental medications include **Fluconazole**, which is administered orally in a pharmaceutical form identified as PHF00017MIG. The maximum daily dose is 400 mg, with a total dose of 200 mg, and the treatment period extends up to 12 weeks. **Fluconazole** is used as a comparator in the study.

Another experimental medication is **Sulfamethoxazole and Trimethoprim**, administered orally in the form PHF00170MIG. The maximum daily dose is 1600 mg, with a total dose of 800 mg, over a 12-week period. This medication also serves as a comparator in the trial.

**Amoxicillin** is included as an experimental treatment, administered orally in the form PHF00231MIG. The maximum daily dose is 3000 mg, with a total dose of 1000 mg, for a duration of 12 weeks. It is used as a comparator in the study.

**Metronidazole** is administered orally in the form PHF675, with a maximum daily dose of 1500 mg and a total dose of 500 mg, over a 12-week period. It is also a comparator in the trial.

**Ciprofloxacin** is another experimental medication, administered orally in the form PHF00134MIG. The maximum daily dose is 1500 mg, with a total dose of 750 mg, for a 12-week period. It serves as a comparator in the study.

**Amoxicillin and Beta-lactamase Inhibitor** is administered orally in the form PHF00231MIG, with a maximum daily dose of 500 mg and a total dose of 1600 mg, over 12 weeks. This medication is used as a comparator in the trial.

**Clindamycin** is administered orally in the form PHF00006MIG, with a maximum daily dose of 2400 mg and a total dose of 300 mg, for a 12-week period. It is used as a comparator in the study.

**Doxycycline** is administered orally in the form PHF00209MIG, with a maximum daily dose of 200 mg and a total dose of 100 mg, over a 12-week period. It serves as a comparator in the trial.

**Linezolid** is administered orally in the form PHF00101MIG, with a maximum daily dose of 1200 mg and a total dose of 600 mg, for a 12-week period. It is used as a comparator in the study.

The non-experimental treatment in the trial is **Sodium Chloride Solution 0.9%**, administered sublingually. The maximum daily dose is 300 units, with a total dose of 300 units, over a 9-week period. This solution is used as a test treatment in the study.

All medications are administered with a focus on participant compliance, monitored through regular assessments to ensure adherence to dosing schedules. The trial aims to evaluate the efficacy of these treatments in subjects with hip or knee prosthesis infections.

The efficacy of the treatment in this clinical trial will be assessed primarily through the evaluation of the **clinical course** of the infection in patients with hip or knee prosthesis infections. The primary endpoint will focus on the presence of exudate, redness of the wound, pain, or other clinical signs of infection. These parameters will be measured to determine the effectiveness of the treatment in reducing clinical symptoms and/or the progression of the infection.

Secondary endpoints will include a safety assessment, which will monitor both local and systemic adverse events. The trial is designed to evaluate the clinical relevance of autovaccines administered through the sublingual mucosa compared to suppressive antibiotic treatment. The trial will follow a schedule that aligns with the standard clinical practice, ensuring that the additional diagnostic or monitoring procedures pose minimal risk or burden to the subjects. The trial is categorized as a low-intervention Phase III study, adapted to clinical practice and the authorized use of the drug.