Evaluation of Safety and Tolerability of TP-122A Bacteriophage Cocktail in Adults with Ventilator-Associated Pneumonia
- Trial ID
- 2025-521533-85-00
- Protocol
- TP-122_101A
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and **tolerability** of multiple doses of TP-122A, administered via nebulization every 8 hours for 7 days, in conjunction with Standard of Care (SoC) in adult subjects with **Ventilator-Associated Pneumonia** (VAP). This is clinically relevant as it aims to ensure that the treatment is safe for patients and can be tolerated without adverse effects, which is crucial for its potential use in clinical settings.
Secondary objectives include:
- Determining the Clinical Response (CR) to TP-122A when administered alongside SoC in patients with VAP.
- Evaluating the Microbiologic Response (MR) compared to SoC alone.
- Assessing the reduction in antibiotic treatment.
- Measuring the number of Mechanical Ventilator (MV) free days.
- Evaluating the duration of Intensive Care Unit (ICU) stay.
- Assessing overall survival.
Participants
The clinical trial focuses on 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 be intubated and on invasive mechanical ventilation in the intensive care unit for at least 48 hours. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include the ability to provide informed consent, either personally or through a legally designated representative, and specific respiratory and microbiological parameters. Participants must not have a diagnosis of new-onset pneumonia within 72 hours before randomization, and they must exhibit new or worsening infiltrates consistent with pneumonia on imaging within 24 hours of the event. Additionally, subjects with childbearing potential are required to have a negative highly sensitive serum pregnancy test at screening. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.
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-122A for the treatment of **ventilator-associated pneumonia** (VAP). 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) in adult subjects. The trial is expected to commence recruitment on August 1, 2025, and conclude by December 1, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, mechanical ventilation status, and absence of new-onset pneumonia within 72 hours before randomization. The study will include follow-up visits to monitor adverse events, clinical laboratory parameters, vital signs, and electrocardiogram (ECG) results. The end-of-study visit will evaluate the primary and secondary endpoints, including the proportion of subjects achieving "Clinical Cure" and microbiological response, time to achieve these outcomes, and overall survival.
The expected length of participant involvement is approximately 7 days of treatment, with additional time for follow-up assessments. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or withdrawal of consent. The trial will compare the TP-122A arm with SoC versus SoC alone, with individual analyses per treatment arm. The study aims to provide valuable insights into the potential of TP-122A as a treatment option for VAP, focusing on safety and efficacy outcomes.
Treatment
The clinical trial involves the administration of an experimental medication, **TP-122**, which is a bacteriophage cocktail formulated as a **suspension**. This investigational product is designed to target **Klebsiella pneumoniae** and **Pseudomonas aeruginosa**. The active substances in TP-122 include a combination of bacteriophages: 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). The suspension is administered via **inhalation** every 8 hours for a duration of 7 days.
In addition to the experimental treatment, participants will receive standard-of-care therapy for **ventilator-associated pneumonia** (VAP). The standard-of-care therapy is not specified in the trial data but typically includes antibiotics and supportive care as per clinical guidelines. The trial is designed to assess the safety and tolerability of the TP-122 bacteriophage cocktail when used in conjunction with standard-of-care treatments.
Participant compliance with the dosing schedule will be monitored throughout the study. The trial aims to ensure that the administration of TP-122 is consistent and adheres to the specified dosing regimen. The study does not include a placebo or comparator treatment, focusing solely on the effects of the TP-122 in combination with standard-of-care therapy.
Efficacy
The efficacy of the bacteriophage cocktail TP-122 for the treatment of **Ventilator-Associated Pneumonia** will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoints include the analysis of the TP-122A arm with Standard of Care (SoC) versus SoC alone, focusing on adverse events, clinical laboratory parameters, vital signs, and electrocardiogram (ECG) results. These assessments will provide a comprehensive evaluation of the treatment's safety and tolerability.
Secondary efficacy endpoints will measure the proportion of subjects achieving "Clinical Cure" (CR) and the time taken to achieve this outcome. Additionally, the study will evaluate the proportion of subjects achieving a Microbiological Response (MR) of "Eradication" or "Presumed Eradication" of the target bacteria, as well as the time to achieve this MR. Other secondary endpoints include the number of days of antibiotic usage, the number of days with mechanical ventilation, the number of days to discharge from the intensive care unit (ICU), and overall survival, defined as all-cause mortality at follow-up.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Able and willing to sign the ICF. If the subject is unable to do so, the legally designated representative should provide consent or in specific situation at discretion of the investigator in emergency situations as per local country regulations and institution specific guidelines. In all cases, once the patient’s clinical situation allows, informed consent will be sought from the patient themselves as soon as possible, even if prior consent was obtained through a legal representative or under emergency regulations.
- Subjects with 18 years old, or older.
- Subjects intubated and on invasive mechanical ventilation in the intensive care unit for at least 48 hours with : - PaO2/FiO₂ ≥ 200 mm g and ≤300 mm g; - 0.30 ≤ FiO2 ≤ 0.60 (FiO2 within 0.3 and 0.6) - Compliance ≥ 30 mL/cm H2O; - Positive End-Expiratory Pressure (PEEP) ≤ 10 cm H2O;
- No diagnosis of new-onset pneumonia within 72 hours before randomisation (subjects with evidence of resolved pneumonia will be eligible)
- New or worsening infiltrate consistent with pneumonia on chest X-ray or CT Scan, within 24 hours of the event of infection of P. aeruginosa.
- New onset respiratory sign or symptom of increase in respiratory demand, evidenced by 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; OR at least two of the following signs: i. 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 ii. Hypothermia (i.e., core body temperature [tympanic, rectal, esophageal] ≤ 35°C [95°F]); and/or iii. White Blood Cell (WBC) count ≥ 10,000 cells/mm³; and/or iv. Leukopenia with total WBC count ≤ 4500 cells/mm³; and/or v. Production of new purulent endotracheal secretions and/or vi. Physical examination findings consistent with pneumonia/ pulmonary consolidation such as auscultatory findings (e.g. rales, rhonchi, and bronchial breath sounds and/or vii. Dullness to percussion
- Microbiological diagnosis of P. aeruginosa infection in the LRT, before randomization. (Demonstrate the presumptive presence of P. aeruginosa using a rapid diagnostic method either microbiological or molecular. Acceptable approaches include: (1) plating the sample on cetrimide selective agar and incubating for 24 hours at 37°C, with P. aeruginosa colonies typically appearing smooth, greenish (due to pyocyanin), and fluorescent under UV light (due to pyoverdine) and being oxidase positive; or (2) performing PCR testing, such as the BIOFIRE® FILMARRAY® Pneumonia Panel plus (bioMérieux) or equivalent methodologies. These methods support patient recruitment based on the presumptive identification of P. aeruginosa as the causative agent of ventilator-associated pneumonia (VAP), in accordance with the diagnostic capabilities and standard procedures of the local laboratory. Patient randomization will proceed based on this presumptive identification. Bacteria identification results from respiratory samples obtained until not more than 48h before screening are accepted).
- Subjects with childbearing potential must have a negative highly sensitive serum pregnancy test at screening. (Male and female subjects of childbearing potential must agree to use highly effective contraception as defined in Section 10.2 from the time of informed consent until at least 30 days after the last dose of IMP.)
Exclusion Criteria
- Moderate to severe acute respiratory distress syndrome (ARDS) or 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.
- Subjects requiring prone position.
- Subjects who are pregnant, breastfeeding, planning pregnancy, or unable/unwilling to comply with the required contraceptive measures descrived in Section 10.2 are excluded from participation.
- Participation in another clinical trial at the time of randomization or prior participation in a clinical trial involving the administration of an IMP within 30 days before randomization or within ‘5 half-lives of the IMP’ (whichever is longer). if the clinical trial in which the patient is or was enrolled is considered relevant to patients with ventilator-associated pneumonia (VAP). The determination of such relevance must be discussed with, and receive prior approval from, the sponsor
- Subjects with active community-acquired bacterial pneumonia, viral or fungal pneumonia (including Pneumocystis jiroveci) are excluded (patients with resolved pneumonia will be eligible). Additionally, subjects with tracheobronchitis (without documented pneumonia), chemical pneumonitis, 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) are also excluded.
- Subjects requiring Airway Pressure Release Ventilation or High Frequency Oscillatory Ventilation. Subjects needing for any form of ECLS/ECMO.
- 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.
- Subjects with severe asthma or reactive airway disease, according to Investigator’s decision.
- History of known hypersensitivity to any component of the investigational product.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Not Yet Recruiting | 02 Mar 2026 | — |
 Portugal | Not Yet Recruiting | 02 Mar 2026 | 19 |
| Netherlands | — | — | 19 |
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 |
Excipient mixture (solvent):Sodium Chloride 0.9% w/v ;Tromethamine TRIS® 0.30% w/v; Polysorbate 80 0.02% w/v; Glycerol 5% v/v; Mannitol 0.6% w/v; Hydrochloric Acid q.s. | Placebo | N/A | — | — | — | N/A |