Phase 1b/2, Open-Label Clinical Trial Evaluating the Safety and Efficacy of Nogapendekin Alfa Inbakicept (NAI) Plus Standard of Care in Critically Ill Adults With Sepsis
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 49
- 主要终点
- 28-Day Survival Rate
研究概览
简要总结
This study will test whether adding an immune-stimulating drug, nogapendekin alfa inbakicept (NAI), to standard intensive care treatment is safe and potentially helpful for adults with sepsis or septic shock.
All participants will receive usual sepsis care. They will also get NAI as an injection under the skin on Day 1, and again on Days 14 and 21 if still in the hospital (and with low lymphocyte counts on Day 21). The study will first focus on safety in 10 patients, then enroll more (total 49) to see how many are alive at 28 days and 90 days, how their white blood cell counts recover, how much organ support they need, and how long they stay in the ICU and hospital.
详细描述
This is a two-part, open-label, single-arm Phase 1b/2 trial evaluating nogapendekin alfa inbakicept (NAI; ANKTIVA®, N-803) plus protocolized guideline-directed standard of care in critically ill adults with sepsis or septic shock and persistent lymphopenia (ALC ≤ 1,000 cells/µL). Part 1 (Phase 1b) is a safety lead-in enrolling 10 participants to characterize safety and tolerability of adding subcutaneous NAI (1.2 mg on Day 1; repeat dosing on Day 14 and Day 21 if still hospitalized and ALC ≤ 1,000) to Surviving Sepsis Campaign-based care. After Safety Review Committee evaluation, Part 2 (Phase 2) will enroll an additional 39 participants (total N=49) to estimate the 28-day survival rate and explore NAI's effect on absolute lymphocyte count recovery, organ support-free days, organ dysfunction (SOFA), ICU and hospital length of stay, and secondary infections. All participants are followed for 90 days from first dose to assess survival and late safety events.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years at the time of informed consent.
- •Admitted to the ICU with sepsis or septic shock per Sepsis 3 criteria, operationalized as a SOFA increase of ≥ 2 points attributable to suspected or confirmed infection; septic shock defined as persistent vasopressor requirement to maintain MAP ≥ 65 mm Hg and serum lactate > 2 mmol/L despite adequate volume resuscitation.
- •ALC ≤ 1,000 cells/µL in two consecutive measurements separated by ≥ 12 hours within the 72 hour screening window.
- •Documented or strongly suspected infection (bacterial, viral, fungal, or mixed) with reasonable diagnostic workup initiated.
- •Receiving guideline-directed standard of care per 2026 Surviving Sepsis Campaign Guidelines, including as clinically appropriate: early empiric broad-spectrum antimicrobials, ≥ 30 mL/kg balanced crystalloid within 3 hours for hypoperfusion or shock, norepinephrine as first line vasopressor (MAP ≥ 65 mm Hg), lung-protective ventilation if mechanically ventilated, glycemic target 144-180 mg/dL, and venous thromboembolism and stress ulcer prophylaxis.
- •Able to receive the first dose of NAI within 72 hours of sepsis recognition, targeted within 12 hours of eligibility confirmation.
- •Ability to obtain written informed consent from the participant or a legally authorized representative.
- •Agreement to practice effective contraception for females of childbearing potential and nonsterile males, with details as in protocol.
排除标准
- •Severe hepatic failure defined as Child Pugh class C with active hepatic encephalopathy at screening.
- •Active malignancy receiving cytotoxic chemotherapy, radiotherapy, or checkpoint inhibitor therapy within 30 days prior to sepsis onset (maintenance hormonal therapy and stable targeted therapies permitted).
- •Hematopoietic stem cell transplant within prior 100 days or active graft versus host disease requiring systemic immunosuppression.
- •Known hypersensitivity to NAI, IL 15, recombinant IL 15 receptor alpha sushi domain, or human IgG1 Fc.
- •Pregnancy or breastfeeding; negative serum pregnancy test required for women of childbearing potential.
- •Active second investigational therapy or participation in another interventional trial within 30 days prior to enrollment.
- •In the Investigator's opinion, a clinical condition or treatment limitation precluding meaningful participation or follow up (e.g., expected death within 24 hours, comfort-care-only orders precluding protocol-mandated assessments).
结局指标
主要结局
28-Day Survival Rate
时间窗: From Day 1 (first NAI dose) through Day 28
Proportion of participants who are alive 28 days after the first dose of nogapendekin alfa inbakicept (NAI). Survival status will be determined by review of hospital records and/or direct contact (in person or by phone) on Day 28 after Day 1 dosing.
次要结局
- Change in Absolute Lymphocyte Count (ALC) From Baseline(Baseline (Day 1 pre-dose) through end of hospital stay (up to 90 days))
- 90-Day Survival Rate(From Day 1 (first NAI dose) through Day 90)
- Proportion of Participants Alive and Free of Organ Support at Day 28(Day 28 after Day 1 (first NAI dose))
- Time to ICU Discharge(From ICU admission to ICU discharge or death (up to 90 days))
- Time to Hospital Discharge(From hospital admission to hospital discharge or death (up to 90 days))
- Incidence of Secondary Infections Through Day 28(From Day 1 through Day 28)
- Change From Baseline in SOFA Score(Baseline (Day 1) through end of ICU stay (up to 90 days))