Phase 1/2a to Assess the Safety and Tolerability of TP-122A for the Treatment of Ventilator-Associated Pneumonia

NCT06370598 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TP-122
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Given the challenges of treating complex cases of VAP caused by P. aeruginosa and K. pneumoniae, TechnoPhage developed a bacteriophage cocktail (TP-122) against those pathogens, aiming to provide a hospital-based add-on therapy to the SoC including antibiotic therapy, administered by nebulization. TP-122 is a bacteriophage cocktail divided in two different components: TP-122A is comprised of three bacteriophages against infections caused by Pseudomonas aeruginosa and TP-122B includes three bacteriophages against K. pneumoniae . For this study, an effective sample of 15 subjects will be randomly allocated into two arms, in a 3:2 ratio, with 9 subjects receiving TP-122A, in addition to SoC, and 6 subjects receiving the SoC alone.

Conditions

Pneumonia, Ventilator-Associated

Outcome Measures

Primary Outcomes (1)

• Evaluate safety and tolerability following nebulization of multiple doses of TP-122A

  Analysis of TP-122A arm with SoC versus SoC alone, and individual analysis per treatment arm of the following assessments: Adverse Events (AEs): 1. Incidence of Treatment-Emergent Adverse Events (TEAEs). 2. Incidence of serious TEAEs. Note: including assessment of seriousness, severity, causality, and outcome.

  Day 0, 3 and Day 7

Secondary Outcomes (4)

• Proportion of subjects achieving "Clinical Cure" CR

  dosing days (1 to 7) and FUp1).

• Time to achieve "Clinical Cure" CR

  Baseline to EOT

• Proportion of subjects achieving "Eradication" or "Presumed Eradication" MR of TP-122A target bacteria

  dosing days (1 to 7), FUp1 and FUp2

• Time to achieve "Eradication" or "Presumed Eradication" MR

  Day o and Day 7

Study Arms (2)

TP-122A with SOC

EXPERIMENTAL

Enrolled subjects in the TP-122A+SoC arm will receive IP every 8 hours for 7 days by nebulization and will be followed-up for 28 days after the last IP administration.

Biological: TP-122A

SOC alone

NO INTERVENTION

Just standard of care will be given to patient

Interventions

TP-122A BIOLOGICAL

Bacteriophage cocktail targeting Psa

TP-122A with SOC

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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;
• Positive End-Expiratory Pressure (PEEP) equal or lower than 10 cm H2O;
• If receiving vasoactive drugs, these must be on a stable dose for the last 24 hours.
• AND at least one of the following:
• i. Hypoxemia \[e.g., PaO2\<60 mmHg while the patient is breathing room air, as determined by Arterial Blood Gas (ABG), or worsening of PaO2/FiO2\]; and/or ii. 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 iii. New onset of suctioned respiratory secretions.
• AND at least one of the following signs:
• iv. 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 v. Hypothermia (i.e., core body temperature \[tympanic, rectal, esophageal\] ≤ 35°C \[95°F\]); and/or vi. White Blood Cell (WBC) count ≥ 10,000 cells/mm³; and/or vii. Leukopenia with total WBC count ≤ 4500 cells/mm³; and/or viii. 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 Endotracheal Aspirates (ETA), Mini Bronchoalveolar Lavage (BAL) or standard BAL throughout fiberoptic bronchoscopy, subjected to Gram staining and/or Polymerase Chain Reaction (PCR) test (e.g., BIOFIRE® FILMARRAY® Pneumonia Panel plus (Biomerieux)).
• \. Subjects with childbearing potential must have a negative highly sensitive serum pregnancy test at screening.

You may not qualify if:

• \. History of any cancer requiring systemic chemotherapy or radiation, in the 5 previous years.
• \. 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, organ transplant, or immunosuppressive therapies (e.g., oral or parenteral corticosteroids, methotrexate, immunomodulators), 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. 6. Currently participating in another clinical trial or having participated in a clinical trial with receipt of an IP in the last 30 days prior to randomization or in the last '5 half-lives of the IP' 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.

Sponsors & Collaborators

• Technophage, SA: lead
• VectorB2B: collaborator

Study Sites (1)

CH Nantes

Nantes, France

Location

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Margarida Barreto, Msc

  Technophage, SA

  STUDY DIRECTOR

Central Study Contacts

Margarida Barreto, Msc

CONTACT

+351215943993; mbarreto@technophage.pt

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2024
• First Posted: April 17, 2024
• Study Start: September 1, 2024
• Primary Completion: May 1, 2025
• Study Completion: June 1, 2025
• Last Updated: April 17, 2024

Record last verified: 2024-04

Locations

FR (1)