Pneumonia - Bacterial, Pseudomonas Aeruginosa Infection
Conditions
Keywords
Acute Pseudomonas Aeruginosa Pneumonia
Brief summary
The purpose of this study is to evaluate the safety and tolerability of a single intravenous dose of MP101 administered in addition to standard antibiotic therapy in adult patients with acute Pseudomonas aeruginosa pneumonia. The study will also assess the pharmacokinetic and pharmacodynamic characteristics of MP101 and its antibacterial activity, including changes in P. aeruginosa burden in sputum and changes in susceptibility to MP101 and concomitant antibiotics.
Detailed description
This is a randomized, double-blind, placebo-controlled, single-dose, dose-escalation phase 1 study in adult patients with acute Pseudomonas aeruginosa pneumonia. Approximately 18 participants will be enrolled at about 6 study sites in Korea. Participants will be assigned to either a low-dose cohort or a high-dose cohort and will receive MP101 or matching placebo in addition to standard antibiotic therapy. Escalation to the high-dose cohort will occur after review of available safety data by the Safety Review Committee. The study is designed to evaluate the safety and tolerability of MP101 and to characterize its pharmacokinetic and pharmacodynamic profile in blood and sputum. The study will also assess antibacterial activity against Pseudomonas aeruginosa, including changes in sputum bacterial burden and changes in susceptibility to MP101 and concomitant antibiotics. Additional exploratory assessments include inflammatory biomarkers and clinical outcome measures in patients with acute pneumonia. After screening within 7 days before dosing, participants will receive study treatment on Day 1 and remain under inpatient observation through Day 8 for safety and PK/PD assessments. Follow-up visits will be conducted on Day 15 and Day 29. Study assessments include adverse events, clinical laboratory tests, vital signs, electrocardiograms, microbiologic evaluations in sputum, and protocol-defined exploratory assessments.
Interventions
BIOLOGICALMP101
This clinical trial is a Phase 1 study with a randomized, double-blind, placebo-controlled, single-dose, sequential dose-escalation design and consists of two dose cohorts. After the safety of the low-dose cohort (Cohort A) is evaluated, dosing will proceed to the high-dose cohort (Cohort B). The investigational product, MP101, is a cocktail formulation comprising two bacteriophages. Participants in Cohort A will receive low dose, and participants in Cohort B will receive high dose. MP101 will be administered as a single intravenous infusion. The placebo is a clear solution with the same appearance as MP101 but without bacteriophages, and it will be administered in the same manner.
DRUGAntibiotics
All study subjects will receive concomitant antibiotic therapy. The choice of the concomitant antibiotic will be based on the results of antibiotic susceptibility testing and will follow the best available therapy, as determined by the investigator.
Sponsors
MicrobiotiX Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects aged 19 years or older. * Clinical diagnosis of acute pneumonia with radiologic evidence of pulmonary infiltrates. * Confirmed Pseudomonas aeruginosa (PA) infection via valid respiratory specimens. * PA isolate demonstrates susceptibility to MP101 and non-susceptibility to current antibiotic therapy. * Adequate organ function as defined by hematological, hepatic, and renal laboratory parameters .
Exclusion criteria
* Persistent septic shock or hemodynamically unstable condition. * Active pulmonary tuberculosis or non-bacterial pneumonia. * Significant pleural effusion or lung abscess requiring therapeutic drainage. * Clinically significant cardiovascular, hepatic, or renal impairment . * Immunocompromised status or hematological malignancies. * Known hypersensitivity to bacteriophages, study components, or concomitant antibiotics. * Participation in another clinical trial within 30 days prior to screening. * Any medical condition that, in the opinion of the investigator, would make the subject unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and frequency of adverse events (AEs), adverse drug reactions (ADRs), serious adverse events (SAEs), and serious adverse drug reactions (SADRs) occurring after administration of MP101. | Throughout the clinical trial period from screening through Day 29 (D29) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of MP101 | Pre-dose, 15 min, 30 min, 1, 2, 4, 8, 24, 48, 72, 96, 120, 168, 336, and 672 hours (Day 29) post-dose. | The maximum concentration of MP101 in plasma observed after administration. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Pre-dose, 15 min, 30 min, 1, 2, 4, 8, 24, 48, 72, 96, 120, 168, 336, and 672 hours (Day 29) post-dose. | The area under the plasma concentration-versus-time curve from time 0 to the last time point with a measurable concentration. |
| Terminal Elimination Half-life (t1/2) of MP101 | Pre-dose, 15 min, 30 min, 1, 2, 4, 8, 24, 48, 72, 96, 120, 168, 336, and 672 hours (Day 29) post-dose. | The time required for the plasma concentration of MP101 to decrease by 50% during the terminal elimination phase. |
| Apparent Volume of Distribution (Vz) of MP101 | Pre-dose, 15 min, 30 min, 1, 2, 4, 8, 24, 48, 72, 96, 120, 168, 336, and 672 hours (Day 29) post-dose. | The theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma. |
| Antibacterial Activity of MP101 Against Pseudomonas aeruginosa (PA) in Sputum | pre-dose, 4, 8, 24, 48, 72, 96, 120, 168, 336, and 672 hours (Day 29) post-dose. | Assessment of the change in bacterial load of Pseudomonas aeruginosa in sputum samples. |
| Change From Baseline in Susceptibility of Pseudomonas Aeruginosa (PA) to MP101 | pre-dose, 120, 168, 336, and 672 hours (Day 29) post-dose. | Evaluation of the change from baseline in the susceptibility of Pseudomonas aeruginosa (PA) isolated from sputum samples to MP101, measured by Phage Susceptibility Testing (PST). |
| Change From Baseline in Susceptibility of Pseudomonas Aeruginosa (PA) to Antibiotics | pre-dose, 120, 168, 336, and 672 hours (Day 29) post-dose. | Evaluation of the change from baseline in the susceptibility of Pseudomonas aeruginosa (PA) isolated from sputum samples to concomitant antibiotics, measured by Antimicrobial Susceptibility Testing (AST) |
Countries
South Korea
Contacts
CONTACTSangmin Lee, Director
PRINCIPAL_INVESTIGATORJun Yong Choi
Severance Hospital
Outcome results
None listed