Clinical trial to assess the safety and tolerability of TP-122A for the treatment of ventilator-associated pneumonia.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01], Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2025-09-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-521533-85-00

ClinicalTrials.gov

NCT06370598

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others

The primary objective of this study is to evaluate the safety and tolerability following nebulization of multiple doses of TP-122A administered for 7 days, in addition to Standard of Care (SoC), in adult subjects with Ventilator-Associated Pneumonia (VAP).

Secondary objectives 1

1. To determine the Clinical Response (CR) to TP-122A when administered, in addition to SoC to patients with VAP and evaluate Microbiologic Response (MR) comparing with SoC alone, antibiotic treatment reduction and Mechanical Ventilator (MV) free days, Intensive Care Unit (ICU) stay and overall Survival.

Conditions and MedDRA coding

Ventilator-Associated Pneumonia

Regulatory references

Scientific advice from competent authorities

National Agency For The Safety Of Medicine And Health Products, Food And Drug Administration, National Authority Of Medicines And Health Products

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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.
2. Subjects with 18 years old, or older.
3. 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;
4. No diagnosis of new-onset pneumonia within 72 hours before randomisation (subjects with evidence of resolved pneumonia will be eligible)
5. 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.
6. 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
7. 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).
8. 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 9

1. 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.
2. Subjects requiring prone position.
3. 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.
4. 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
5. 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.
6. Subjects requiring Airway Pressure Release Ventilation or High Frequency Oscillatory Ventilation. Subjects needing for any form of ECLS/ECMO.
7. 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.
8. Subjects with severe asthma or reactive airway disease, according to Investigator’s decision.
9. History of known hypersensitivity to any component of the investigational product.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Analysis of TP-122A arm with SoC versus SoC alone, and individual analysis per treatment arm of the following assessments: Adverse Events (AEs), Clinical laboratory parameters, Vital signs, Eletrocardiogram (ECG)

Secondary endpoints 8

1. Proportion of subjects achieving “Clinical Cure” (CR)
2. Time to achieve “Clinical Cure”.
3. Proportion of subjects achieving Microbiological Response (MR) of “Eradication” or “Presumed Eradication” of TP-122A target bacteria
4. Time to achieve MR “Eradication” or “Presumed Eradication”.
5. Number of days of antibiotic usage.
6. Number of days with MV.
7. Number of days to discharge from ICU.
8. Overall Survival: all-cause mortality, at FUp2.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Sponsor organisation

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Address

Edificio Egas Monia Sala A8, Avenida Professor Egas Moniz Piso 2 Avenida Professor Egas Moniz Piso 2

City

Lisbon

Postcode

1649-028

Country

Portugal

Scientific contact point

Organisation

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Contact name

Sofia Corte Real

Public contact point

Organisation

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Contact name

Sofia Corte Real

Locations

2 EU/EEA countries · 8 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 24 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