Phase 3 Randomized, Blinded, Placebo-Controlled 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
概览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 10
- 主要终点
- 28-day all-cause mortality
概览
简要总结
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.
详细描述
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:
- 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.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
This is a double-blind study, meaning that participants, treating physicians, and most study personnel and sponsor staff are unaware of which treatment (active drug or placebo) a participant receives. Blinding is maintained through the use of identical-looking active drugs and placebos.
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, adult participants of any gender.
- •Critically ill adults requiring admission to an ICU-unit due to severe community acquired pneumonia.
- •Severe CAP is defined by the presence of one major criterion or at least three minor criteria:
- •Major Criteria (any one = severe CAP):
- •Respiratory failure requiring mechanical ventilation
- •Septic shock requiring vasopressors to maintain blood pressure
- •Minor Criteria (≥3 indicates severe CAP):
- •Tachypnea: Respiratory rate ≥ 30 breaths/min
- •Hypoxemia: PaO2/FiO2 ratio ≤ 200
- •Multilobar infiltrates on chest imaging
排除标准
- •Hematologic malignancies (eg, active leukemia and lymphoma, not in remission).
- •Post CAR-T cells therapy or hematopoietic cell transplant for ALL, NHL or Multiple Myeloma less than 3 months prior to enrollment.
- •Participant diagnosed with cytokine release syndrome.
- •Participant receiving colony stimulating factors eg, G-CSF.
- •Clinical history or radiological imaging suggesting aspiration of gastric content.
- •Participant with advanced dementia or prolonged bedridden status.
- •Pregnancy or breastfeeding.
- •High-dose immunosuppressive therapy at baseline: eg, \> 0.5 mg/kg prednisone (or equivalent). Note: Use of low-dose corticosteroids for septic shock or ARDS (eg, dexamethasone 6 mg/day for ARDS) is not an exclusion, as it is standard care such use will be recorded and balanced between arms.
- •Uncontrolled autoimmune or inflammatory disease requiring immunosuppressive therapies (to avoid confounding immune effects or exacerbation).
- •Life expectancy \< 24-48 hours or moribund condition despite care (Investigator judgment that participant will not survive long enough to benefit or be evaluated).
结局指标
主要结局
28-day all-cause mortality
时间窗: 30 days after the last dose of study drug
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).
次要结局
- ALC count(From randomization through 28 days following randomization.)
- Ventilator-Free days (VFD) through Day 28.(Through 28 days following randomization.)
- Number of ICU free days through Day 28.(Through 28 days following randomization.)
- Number of antibiotic free days through Day 28.(Through 28 days following randomization.)
- Number of days alive and free of organ support through 28 days.(Through 28 days following randomization.)
- Time from first administration of study drug to ICU discharge.(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.(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.(From randomization through 90 days following randomization.)
- 90-day all-cause mortality.(Through 90 days following randomization.)