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] - Respiratory Tract Diseases [C08]

Decision date (initial)

2024-02-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

TechnoPhage S.A.

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, every 8 hours, for 7 days, in addition to SoC, in adult subjects with VAP

Secondary objectives 1

1. To determine the CR to TP-122A when administered, in addition to SoC to patients with VAP and evaluate MR comparing with SoC alone, MV free days as well as ICU stay.

Conditions and MedDRA coding

Ventilator-Associated Pneumonia

Regulatory references

Scientific advice from competent authorities

Comite De Protection Des Personnes Sud Mediterrannee IV, National Agency For The Safety Of Medicine And Health Products

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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

Exclusion criteria 11

1. History of any cancer requiring systemic chemotherapy or radiation, in the 5 previous years.
2. Subjects with severe asthma or reactive airway disease
3. 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.
4. 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.
5. 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).
6. Being pregnant or breastfeeding
7. 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).
8. 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).
9. Subjects requiring Airway Pressure Release Ventilation or High Frequency Oscillatory Ventilation.
10. 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.
11. Individuals deprived of liberty or placed under the authority of a tutor

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Analysis of TP-122A arm with SoC versus SoC alone, and individual analysis per treatment arm of the following assessments:
2. 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,
3. 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)
4. 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).
5. 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).

Secondary endpoints 7

1. Proportion of subjects achieving “Clinical Cure” clinical response (CR) (time frames: dosing days (1 to 7) and FUp1
2. Time to achieve “Clinical Cure” CR
3. 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
4. Time to achieve “Eradication” or “Presumed Eradication” MR
5. Number of days with mechanical ventilator (MV), from first dose of investigational product (IP) to FUp1.
6. Number of days in ICU from first dose of IP to FUp2
7. Survival: all-cause mortality, at FUp2.

Investigational products

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

Test 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

Margarida Barreto

Public contact point

Organisation

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Contact name

Margarida Barreto

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications