Sepsis, Septic Shock
Conditions
Keywords
Sepsis, Septic shock, Critical illness, Intensive care unit, Persistent lymphopenia, Absolute lymphocyte count, Nogapendekin alfa inbakicept, N-803, ANKTIVA, IL-15 receptor agonist, Immunotherapy in sepsis
Brief summary
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.
Detailed description
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.
Interventions
Subcutaneous administration of nogapendekin alfa inbakicept (NAI; N-803, ANKTIVA®), a recombinant human IL-15 receptor agonist complex (IL-15N72D:IL-15RαSu/IgG1 Fc), at a fixed dose of 1.2 mg (0.6 mL at 2 mg/mL) on Day 1 (within 72 hours of sepsis recognition), with additional 1.2 mg doses on Day 14 if still hospitalized and on Day 21 if still hospitalized with ALC ≤ 1,000 cells/µL, given in combination with protocolized Surviving Sepsis Campaign-based standard of care.
Sponsors
ImmunityBio, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm trial of NAI plus standard of care in critically ill adults with sepsis or septic shock.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years at the time of informed consent. 2. 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. 3. ALC ≤ 1,000 cells/µL in two consecutive measurements separated by ≥ 12 hours within the 72 hour screening window. 4. Documented or strongly suspected infection (bacterial, viral, fungal, or mixed) with reasonable diagnostic workup initiated. 5. 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. 6. Able to receive the first dose of NAI within 72 hours of sepsis recognition, targeted within 12 hours of eligibility confirmation. 7. Ability to obtain written informed consent from the participant or a legally authorized representative. 8. Agreement to practice effective contraception for females of childbearing potential and nonsterile males, with details as in protocol.
Exclusion criteria
1. Severe hepatic failure defined as Child Pugh class C with active hepatic encephalopathy at screening. 2. 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). 3. Hematopoietic stem cell transplant within prior 100 days or active graft versus host disease requiring systemic immunosuppression. 4. Known hypersensitivity to NAI, IL 15, recombinant IL 15 receptor alpha sushi domain, or human IgG1 Fc. 5. Pregnancy or breastfeeding; negative serum pregnancy test required for women of childbearing potential. 6. Active second investigational therapy or participation in another interventional trial within 30 days prior to enrollment. 7. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 28-Day Survival Rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Absolute Lymphocyte Count (ALC) From Baseline | Baseline (Day 1 pre-dose) through end of hospital stay (up to 90 days) | Change in absolute lymphocyte count (cells/µL) from baseline (Day 1 pre-dose) at each assessment through the end of hospital stay, using local complete blood counts with differential collected at least every 3 days. |
| 90-Day Survival Rate | From Day 1 (first NAI dose) through Day 90 | Proportion of participants who are alive 90 days after the first dose of nogapendekin alfa inbakicept (NAI). Survival status will be determined by review of records and/or direct contact (in person or by phone) on Day 90 after Day 1 dosing. |
| Change From Baseline in SOFA Score | Baseline (Day 1) through end of ICU stay (up to 90 days) | Change from baseline in Sequential Organ Failure Assessment (SOFA) score at each daily intensive care unit (ICU) assessment. The SOFA score evaluates dysfunction across six organ systems: respiratory, coagulation, hepatic, cardiovascular, central nervous system, and renal. Each organ system is scored from 0 to 4, resulting in a total score ranging from 0 to 24. Higher scores indicate greater organ dysfunction and a worse clinical outcome. Change from baseline is calculated as the score at each daily ICU assessment minus the baseline score; a positive change indicates worsening organ dysfunction, while a negative change indicates improvement. |
| Time to ICU Discharge | From ICU admission to ICU discharge or death (up to 90 days) | Number of days from ICU admission at the index sepsis episode to ICU discharge, with death before ICU discharge treated as a competing event in analysis. |
| Time to Hospital Discharge | From hospital admission to hospital discharge or death (up to 90 days) | Number of days from hospital admission at the index sepsis episode to hospital discharge, with death before discharge treated as a competing event in analysis. |
| Proportion of Participants Alive and Free of Organ Support at Day 28 | Day 28 after Day 1 (first NAI dose) | Proportion of participants who are alive and not requiring mechanical ventilation, vasopressors, or renal replacement therapy on Day 28 after the first NAI dose. Organ support status will be determined from ICU/hospital records. |
| Incidence of Secondary Infections Through Day 28 | From Day 1 through Day 28 | Number and proportion of participants who develop one or more new infections after enrollment that are distinct from the index infection, based on clinical diagnosis and culture or other microbiologic testing. |
Contacts
CONTACTJoseph Ward
CONTACTJim Albert
STUDY_CHAIRLennie Sender, MD
ImmunityBio, Inc.
Outcome results
None listed