Nogapendekin Alfa-Inbakicept and iNKT Cells for Critically Ill Adults With Severe Community-Acquired Pneumonia (With or Without Sepsis/ARDS)
brief summary
This Phase 2 study tests whether adding two immune therapies - nogapendekin alfa-inbakicept (NAI) and off-the-shelf iNKT cell infusions - to standard care can safely help critically ill adults with severe community-acquired pneumonia (CAP) (with or without sepsis/ARDS) recover. The study will give NAI by subcutaneous injection (Days 1 and 10) and one IV dose of iNKT cells (Day 3), then follow participants for 90 days.
detailed description
Phase 2, single-arm study in up to 20 critically ill adults with severe community-acquired pneumonia (CAP) (with or without sepsis/ARDS) and lymphopenia (ALC \<1,500/µL). The study evaluates the safety, tolerability, and preliminary efficacy of combining an IL-15 superagonist (nogapendekin alfa-inbakicept, NAI) with an allogeneic invariant natural killer T cell product (iNKT cells) added to standard ICU care.
Key elements
Population: Adults (≥18) admitted to ICU for severe CAP within 72 hours, meeting IDSA/ATS severe CAP criteria (≥1 major or ≥3 minor) and on antibiotics.
Planned enrollment: up to 20 participants (≈40 screened).
Intervention schedule:
Day 1: NAI subcutaneous (≤50 kg → 15 µg/kg; \>50 kg → fixed 1 mg). Day 3: Single IV infusion of iNKT cells (1 × 10\^9 cells). Day 10: Second NAI subcutaneous dose (same dosing as Day 1). Concomitant care: all participants receive guideline-based standard of care for CAP/sepsis/ARDS (antibiotics, organ support, lung-protective ventilation, vasopressors, low-dose steroids as indicated, etc.).
Safety oversight: continuous ICU monitoring; Sponsor Drug Safety review of SAEs; Safety Review Committee (SRC) reviews safety after first 5 participants and oversees stopping rules. Predefined toxicity rules and management algorithms for infusion reactions, CRS, and ICANS are specified.
Primary endpoints: safety/tolerability (TEAEs, SAEs, grade ≥3 AEs) and 28-day all-cause mortality.
Secondary endpoints: absolute lymphocyte count recovery, ventilator-free days, ICU-free days, antibiotic-free days, days free from organ support, time to ICU/hospital discharge, incidence of secondary infections through Day 28, and 90-day mortality.
Exploratory endpoints: serum cytokines, NK and T-cell expansion and activation/exhaustion markers, monocyte HLA-DR, quantification and persistence of donor iNKT cells (Days 1, 7, 14, 28).
Duration per participant: treatment up to 10 days; follow-up to 90 days after first dose.
Stopping/discontinuation: specified criteria for permanent discontinuation (e.g., drug-related Grade ≥3 organ toxicity, Grade ≥3 CRS/ICANS, intolerable infusion reactions), SRC stopping rules (including treatment-related death or clustered severe toxicities).
official title
Phase 2 Study Evaluating Nogapendekin Alfa Inbakicept and iNKT Cells in Critically Ill Adults With Severe Community-Acquired Pneumonia With or Without Sepsis/Acute Respiratory Distress Syndrome.