DEMERECVIRIDAE BACTERIOPHAGE AGAINST KLEBESIELLA PNEUMONIAE (113.073 BP); DREXLERVIRIDAE BACTERIOPHAGE AGAINST KLEBESIELLA PNEUMONIAE (45.423 BP); MYOVIRIDAE BACTERIOPHAGE AGAINST KLEBESIELLA PNEUMONIAE (169.802 BP); MYOVIRIDAE BACTERIOPHAGE AGAINST PSEUDOMONAS AERUGINOSA (65.855 BP); MYOVIRIDAE BACTERIOPHAGE AGAINST PSEUDOMONAS AERUGINOSA (92.792 BP); SIPHOVIRIDAE BACTERIOPHAGE AGAINST PSEUDOMONAS AERUGINOSA (43.020 BP) for Ventilator-associated pneumonia

Inclusion criteria

• {"criterion_text":"- 1. 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."}
• {"criterion_text":"- 2. Subjects with 18 years old, or older."}
• {"criterion_text":"- 3. 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 4. 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))."}
• {"criterion_text":"- 5. Female subjects of childbearing potential must have a negative highly sensitive pregnancy test at screening."}
• {"criterion_text":"- 6. Subject registered into a social security scheme"}

Exclusion criteria

• {"criterion_text":"- History of any cancer requiring systemic chemotherapy or radiation, in the 5 previous years."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Individuals deprived of liberty or placed under the authority of a tutor"}
• {"criterion_text":"- Subjects with severe asthma or reactive airway disease"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Being pregnant or breastfeeding"}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Subjects requiring Airway Pressure Release Ventilation or High Frequency Oscillatory Ventilation."}

Primary endpoints

• {"endpoint_text":"- Analysis of TP-122A arm with SoC versus SoC alone, and individual analysis per treatment arm of the following assessments:","definition_or_measurement_approach":""}
• {"endpoint_text":"- 1.a. Adverse Events (AEs): a. Incidence of treatment-emergent adverse events (AE). b. Incidence of treatment-emergent serious adverse events (SAEs). Note: including analysis of seriousness, severity, causality,","definition_or_measurement_approach":"Incidence of treatment-emergent AEs and SAEs; includes analysis of seriousness, severity, causality."}
• {"endpoint_text":"- 1.b. Clinical laboratory parameters c. Changes from baseline in clinical laboratory parameters. d. Clinical laboratory parameters abnormalities shift tables. Note: Time frames: dosing days 3, End Of Treatment (EOT)/Early Discontinuation (ED) and followup period (FUp1 and Fup2)","definition_or_measurement_approach":"Changes from baseline and shift tables in clinical laboratory parameters at dosing day 3, EOT/ED, and follow-up periods FUp1 and FUp2."}
• {"endpoint_text":"- 1.c. Vital signs e. Changes from baseline in vital signs. f. Vital signs abnormalities shift tables. Note: Time frames: dosing days (3 and 7/EOT), and follow-up period (FUp1 and FUp2).","definition_or_measurement_approach":"Changes from baseline in vital signs and abnormalities shift tables at dosing days 3 and 7/EOT and follow-up periods FUp1 and FUp2."}
• {"endpoint_text":"- 1.d. Electrocardiogram (ECG) g. Changes from baseline in ECG. h. ECG abnormalities shift tables. Note: Time frames: baseline, dosing day 3, EOT/ED, and FUp (FUp1 and FUp2).","definition_or_measurement_approach":"Changes from baseline in ECG and ECG abnormalities shift tables at baseline, dosing day 3, EOT/ED, and follow-up FUp1 and FUp2."}

Secondary endpoints

• {"endpoint_text":"- Proportion of subjects achieving “Clinical Cure” clinical response (CR) (time frames: dosing days (1 to 7) and FUp1","definition_or_measurement_approach":"Proportion achieving Clinical Cure (CR); assessed during dosing days 1–7 and at FUp1."}
• {"endpoint_text":"- Time to achieve “Clinical Cure” CR","definition_or_measurement_approach":"Time-to-event measurement for achieving Clinical Cure."}
• {"endpoint_text":"- Proportion of subjects achieving “Eradication” or “Presumed Eradication” microbiological response (MR) of TP-122A target bacteria (time frames: dosing days (1 to 7), FUp1 and FUp2","definition_or_measurement_approach":"Proportion achieving microbiological Eradication or Presumed Eradication assessed during dosing days 1–7 and at FUp1 and FUp2."}
• {"endpoint_text":"- Time to achieve “Eradication” or “Presumed Eradication” MR","definition_or_measurement_approach":"Time-to-event measurement for microbiological Eradication or Presumed Eradication."}
• {"endpoint_text":"- Number of days with mechanical ventilator (MV), from first dose of investigational product (IP) to FUp1.","definition_or_measurement_approach":"Count of MV days from first IP dose to FUp1."}
• {"endpoint_text":"- Number of days in ICU from first dose of IP to FUp2","definition_or_measurement_approach":"Count of ICU days from first IP dose to FUp2."}
• {"endpoint_text":"- Survival: all-cause mortality, at FUp2.","definition_or_measurement_approach":"All-cause mortality assessed at FUp2."}

France

Earliest CTIS Part Ii Submission Date

02-01-2024

Latest Decision Or Authorization Date

26-02-2024

Processing Time Days

55

Number Of Sites

2

Number Of Participants

15

Primary sponsor

Full Name

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Portugal