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.
试验速览
- 阶段
- 2 期
- 状态
- 撤回
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 105 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Critically ill adult requiring ICU admission due to severe community acquired pneumonia (CAP), defined by ≥1 major criterion or ≥3 minor criteria (IDSA/ATS):
- •Major: respiratory failure requiring mechanical ventilation OR septic shock requiring vasopressors.
- •Minor: tachypnea (RR ≥ 30), PaO2/FiO2 ≤ 200, multilobar infiltrates, new confusion/disorientation, BUN ≥ 20 mg/dL, platelet count < 100,000/µL, core temperature < 36.0°C, hypotension requiring aggressive fluid resuscitation.
- •Hospital admission with diagnosis of CAP within 72 hours.
- •Lymphopenia: absolute lymphocyte count (ALC) < 1,500/µL (not secondary to chemotherapy).
- •Receiving antibiotics for CAP (at least one dose since ICU admission).
- •Informed consent obtainable from participant or legally authorized representative.
排除标准
- •Hematologic malignancy (e.g., active leukemia or lymphoma not in remission).
- •Post CAR T therapy or hematopoietic cell transplant for ALL, NHL, or multiple myeloma < 3 months prior to enrollment.
- •Current diagnosis of cytokine release syndrome.
- •Receiving colony stimulating factors (e.g., G CSF).
- •Clinical history or imaging suggesting aspiration of gastric contents.
- •Advanced dementia or prolonged bedridden status.
- •Pregnancy or breastfeeding.
- •High dose immunosuppressive therapy at baseline (e.g., > 0.5 mg/kg prednisone or equivalent). (Low dose corticosteroids for septic shock/ARDS per SOC permitted.)
- •Uncontrolled autoimmune or inflammatory disease requiring immunosuppressive therapies.
- •Life expectancy < 24-48 hours or moribund condition despite care (investigator judgment).
- •Active uncontrolled bleeding or intracerebral hemorrhage.
- •Known hypersensitivity to ingredients used in the cell product formulation (e.g., DMSO).
- •Treated by antibiotics for the current respiratory infection for more than seven days at time of hospitalization (unless culture/sensitivity indicates resistant organism to administered antibiotics).
- •Known active viral hepatitis A, B, or C.
- •Investigator judgment that participation is not in the participant's best interest or participant is unsuitable for enrollment.