Evaluation of Safety and Tolerability of TP-122 Bacteriophage Cocktail in Adult Patients with Ventilator-Associated Pneumonia
- Trial ID
- 2023-508825-29-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and **tolerability** of multiple doses of the bacteriophage cocktail TP-122A, administered via nebulization every 8 hours for 7 days, in conjunction with the standard of care (SoC) in adult patients with **ventilator-associated pneumonia** (VAP). This assessment is crucial as it aims to ensure that the treatment is safe for patients and can be tolerated without significant adverse effects, which is fundamental for the potential integration of TP-122A into clinical practice for managing VAP.
Secondary objectives include determining the clinical response (CR) to TP-122A when added to SoC, and evaluating the microbiological response (MR) compared to SoC alone. Additionally, the study aims to assess the number of mechanical ventilation (MV) free days and the length of intensive care unit (ICU) stay. These objectives are important for understanding the potential benefits of TP-122A in improving patient outcomes and reducing healthcare resource utilization in the treatment of VAP.
Participants
The clinical trial focuses on evaluating the safety and tolerability of TP-122A in adult subjects diagnosed with **Ventilator-Associated Pneumonia** (VAP). The study population includes both male and female participants aged 18 years and older. Participants are required to have stable ventilatory requirements and a microbiological diagnosis of Pseudomonas aeruginosa infection in the lower respiratory tract. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants' general health status includes the ability to maintain stable oxygenation levels and, if applicable, stable doses of vasoactive drugs. Female participants of childbearing potential must have a negative pregnancy test at screening. The selection criteria ensure that participants are registered in a social security scheme, and informed consent is obtained either directly from the subjects or through a representative, as per local regulations.
Plans and Procedures
The clinical trial is designed as a **randomized**, parallel, open-label, Phase 1/2a study to evaluate the safety and tolerability of the bacteriophage cocktail TP-122, specifically targeting **ventilator-associated pneumonia** (VAP). The trial will involve adult subjects who meet specific inclusion criteria, such as being 18 years or older and having a stable ventilatory requirement. The primary objective is to assess the safety and tolerability of multiple doses of TP-122A, administered via **inhalation** every 8 hours for 7 days, in addition to the standard of care (SoC). The trial is expected to commence recruitment on April 1, 2024, and conclude by May 15, 2025.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as microbiological diagnosis of **Pseudomonas aeruginosa** infection in the lower respiratory tract. Following randomization, subjects will receive the investigational product and attend dosing visits on days 1 to 7. The primary endpoints include the incidence of treatment-emergent adverse events and changes in clinical laboratory parameters, vital signs, and electrocardiograms. Secondary endpoints focus on the clinical and microbiological response, including the proportion of subjects achieving "Clinical Cure" and "Eradication" of target bacteria.
Participants will be involved in the study for the duration of the treatment period and subsequent follow-up visits, which include two follow-up assessments (FUp1 and FUp2) to monitor long-term outcomes such as survival and time spent on mechanical ventilation. The expected length of participant involvement is approximately 30 days, including the treatment and follow-up periods. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or withdrawal of consent by the participant or their legal representative. The trial aims to provide valuable insights into the safety and efficacy of TP-122A in treating VAP, contributing to the development of novel therapeutic options for this condition.
Treatment
The clinical trial involves the administration of an experimental medication, **TP-122**, which is a bacteriophage cocktail designed for the treatment of **ventilator-associated pneumonia**. TP-122 is formulated as a **suspension** and is administered via **inhalation**. The treatment regimen consists of multiple doses of TP-122, specifically every 8 hours, for a duration of 7 days. The primary objective of the study is to evaluate the safety and tolerability of this regimen in adult subjects.
TP-122 contains a combination of bacteriophages targeting **Klebsiella pneumoniae** and **Pseudomonas aeruginosa**. The active substances include Demerecviridae bacteriophage against Klebsiella pneumoniae (113.073 BP), Drexlerviridae bacteriophage against Klebsiella pneumoniae (45.423 BP), Myoviridae bacteriophage against Klebsiella pneumoniae (169.802 BP), Myoviridae bacteriophage against Pseudomonas aeruginosa (65.855 BP), Myoviridae bacteriophage against Pseudomonas aeruginosa (92.792 BP), and Siphoviridae bacteriophage against Pseudomonas aeruginosa (43.020 BP). These bacteriophages are structurally diverse substances, each with a specific target within the bacterial species.
In addition to the experimental treatment, participants will receive standard-of-care (SoC) therapy as part of the study protocol. The combination of TP-122 with SoC aims to enhance the therapeutic effect against the bacterial pathogens responsible for ventilator-associated pneumonia. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment regimen.
Efficacy
The efficacy of the investigational product TP-122A in the treatment of **Ventilator-Associated Pneumonia (VAP)** will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on safety and tolerability, including the incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs), changes from baseline in clinical laboratory parameters, vital signs, and electrocardiogram (ECG) results. These parameters will be measured at specific time frames: dosing days 3 and 7, end of treatment (EOT) or early discontinuation (ED), and follow-up periods (FUp1 and FUp2).
Secondary endpoints will evaluate the clinical and microbiological response to the treatment. The proportion of subjects achieving a "Clinical Cure" and the time to achieve this response will be recorded. Additionally, the study will assess the proportion of subjects achieving "Eradication" or "Presumed Eradication" of the target bacteria, as well as the time to achieve these microbiological responses. Other secondary measures include the number of days subjects remain on mechanical ventilation and in the intensive care unit (ICU) from the first dose of the investigational product to follow-up periods, and survival rates, specifically all-cause mortality at FUp2.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subjects able and willing to sign the ICF. If the subject is unable to do so, the family, a trusted person or a relative should provide consent, as per local regulations.
- Subjects with 18 years old, or older.
- Subjects with VAP, with stable ventilatory requirements defined as: PaO2/FiO2 not lower than 200 mm Hg; FiO2 ≤ 0.60; Compliance not lower than 30 mL/cm H2O; PEEP equal or lower than 10 cm H2O; If receiving vasoactive drugs, these must be on a stable dose for the last 24 hours.
- 3.a. At least one of the following: Hypoxemia [e.g., PaO2 < 60 mmHg while the patient is breathing room air, as determined by ABG, or worsening of PaO2/FiO2]; And/or need for acute changes in the ventilator support system to enhance oxygenation, as determined by worsening oxygenation (need to increase FiO2 by 20% or more to maintain oxygen saturation), or needed changes in the amount of PEEP; And/or new onset of suctioned respiratory secretions
- 3.b. At least one of the following signs: Documented fever (i.e., core body temperature [tympanic, rectal, esophageal] ≥ 38°C [100.4ºF], oral temperature ≥ 37.5°C [99.5ºF], or axillary temperature ≥ 37°C [98.6ºF]); And/or hypothermia (i.e., core body temperature [tympanic, rectal, esophageal] ≤ 35°C [95°F]); And/or WBC count ≥ 10,000 cells/mm³; And/or leukopenia with total WBC count ≤ 4500 cells/mm³; And/or v. Greater than 15% immature neutrophils (bands) noted on peripheral blood smear.
- Microbiological diagnosis of P. aeruginosa infection in the LRT, before randomization. Diagnosis: cultures obtained by ETA, mini BAL or standard BAL throughout fiberoptic bronchoscopy, subjected to Gram staining and/or PCR test (e.g. BIOFIRE® FILMARRAY® Pneumonia Panel plus (Biomerieux)).
- Female subjects of childbearing potential must have a negative highly sensitive pregnancy test at screening.
- Subject registered into a social security scheme
Exclusion Criteria
- History of any cancer requiring systemic chemotherapy or radiation, in the 5 previous years.
- Subjects with severe asthma or reactive airway disease
- A condition that, in the opinion of the Investigator, could compromise the well-being of the subject, or the course of the study, or prevent the subject from meeting/performing any study requirements/procedures.
- Immunocompromised subjects due to illness, or organ transplant, or immunosuppressive therapies (e.g., oral or parenteral corticosteroids, methotrexate, immune modulators), in the last 3 months prior to screening.
- Treatment with ad hoc low dose inhaled corticosteroids, in the last 2 weeks prior to randomization (except hydrocortisone and equivalent doses of prednisone and methylprednisolone).
- Being pregnant or breastfeeding
- Currently participating in another clinical trial or having participated in a clinical trial with receipt of an investigational product in the last 30 days prior to randomization or in the last ‘5 half-lives of the investigational product’ prior to randomization (whichever is longer).
- Subjects with known community-acquired bacterial pneumonia, or viral or fungal (including Pneumocystis jiroveci) pneumonia (except for subjects that had SARS-CoV-2 related pneumonia more than 6 months before randomization, that do not require long-term oxygen therapy (LTOT)), or tracheobronchitis (without documented pneumonia), or chemical pneumonitis, or post-obstructive pneumonia (except for subjects with a mild severity disease, that do not require pulmonary function tests); or tracheostomy (except for subjects that have tracheostomy performed while being hospitalised in the ICU).
- Subjects requiring Airway Pressure Release Ventilation or High Frequency Oscillatory Ventilation.
- Subjects with pleural effusions (or empyema) requiring therapeutic drainage, or lung abscess, or bronchiectasis; or cystic fibrosis, or acute exacerbation of chronic bronchitis, or active pulmonary tuberculosis; or with stage IV congestive heart failure, or cirrhotic liver disease.
- Individuals deprived of liberty or placed under the authority of a tutor
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Yet Recruiting | 01 Apr 2024 | 15 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
TP-122 | Test | SUSPENSION | INHALATION USE | — | — | PRD10897256 |