This is a Phase 3, randomized, blinded, and placebo-controlled clinical trial investigating a new combination treatment for critically ill adults who have severe community-acquired pneumonia, especially if they also have sepsis or acute respiratory distress syndrome. The study aims to determine if adding the experimental agents, Nogapendekin Alfa Inbakicept and iNKT cells, to standard medical care can reduce the 28-day all-cause mortality rate compared to standard care alone with a placebo.
This multi-center, randomized, blinded, and placebo-controlled Phase 3 study aims to address the high mortality and complication rates associated with severe community-acquired pneumonia (CAP) in critically ill adults, particularly those experiencing immune deficiency like lymphopenia or immunoparalysis. Current standard treatments for severe CAP focus on infection control and organ support but often do not directly restore the patient's compromised immune function. This trial investigates a novel immunotherapeutic approach using a combination of two agents: 1. Nogapendekin Alfa Inbakicept (NAI): An IL-15 receptor agonist designed to activate natural killer (NK) and CD8+ T-cells, aiming to enhance the body's immune competence. 2. iNKT Cells (invariant natural killer T cells): An allogeneic cell therapy intended to rapidly orchestrate both innate and adaptive immune responses. The central hypothesis is that this combination therapy, when added to standard of care treatments, can reverse immune dysfunction, clear infections, regulate inflammation, and ultimately improve survival and reduce severe complications such as secondary infections and prolonged organ support requirements in this vulnerable patient population. The study will meticulously assess the safety and efficacy of this combined approach, building on promising signals from earlier research.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
10
NAI is a soluble complex consisting of two protein subunits of a human IL-15 variant (nogapendekin alfa) bound with high affinity to a dimeric human IL 15Rα sushi domain/human IgG1 Fc fusion protein (inbakicept).
Allogeneic invariant NKT (iNKT) cell therapy - an off-the-shelf cell therapy that can rapidly orchestrate both innate and adaptive immunity.
28-day all-cause mortality
Up to Day 28 from randomization. (Participants lost to follow-up before Day 28 will be censored at their last known date alive; participants alive on Day 28 will be censored at Day 28).
Time frame: 30 days after the last dose of study drug
ALC count
Absolute Lymphocyte Count
Time frame: From randomization through 28 days following randomization.
Ventilator-Free days (VFD) through Day 28.
The number of days a participant is free from mechanical ventilation.
Time frame: Through 28 days following randomization.
Number of ICU free days through Day 28.
The number of days a participant is free from being in the Intensive Care Unit.
Time frame: Through 28 days following randomization.
Number of antibiotic free days through Day 28.
The number of days a participant is free from antibiotic treatment.
Time frame: Through 28 days following randomization.
Number of days alive and free of organ support through 28 days.
The number of days a participant is alive and does not require organ support.
Time frame: Through 28 days following randomization.
Time from first administration of study drug to ICU discharge.
The duration from the first dose of study drug until the participant is discharged from the Intensive Care Unit.
Time frame: From first study drug administration until ICU discharge, assessed up to 90 days; ICU discharge date documented from medical record (participants not discharged by Day 90 censored at Day 90; deaths prior to discharge counted as competing events).
Time from first administration of study drug to hospital discharge.
The duration from the first dose of study drug until the participant is discharged from the hospital.
Time frame: From first study drug administration until hospital discharge, assessed up to 90 days; hospital discharge date documented from medical record (participants not discharged by Day 90 censored at Day 90; deaths prior to discharge counted as competing events
Incidence of secondary infections through Day 28 and for the entire study.
The occurrence rate of infections that develop after the start of study treatment.
Time frame: From randomization through 90 days following randomization.
90-day all-cause mortality.
Death from any cause.
Time frame: Through 90 days following randomization.
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