NAI for Sepsis With Persistent Lymphopenia

Phase 2, Randomized, Open-Label Clinical Trial Evaluating Nogapendekin Alfa Inbakicept in Combination With Standard of Care Versus Standard of Care Alone in Critically Ill Adults With Sepsis and Persistent Lymphopenia

This is a Phase 2, randomized, open-label study evaluating the safety and efficacy of nogapendekin alfa inbakicept (NAI, ANKTIVA®) in combination with standard of care versus standard of care alone in critically ill adults with sepsis and persistent lymphopenia. The study aims to determine whether NAI can improve 28-day mortality by addressing the immunosuppressive phase of sepsis characterized by persistent lymphopenia (absolute lymphocyte count <1,000 cells/µL). Participants will be randomized 1:1 to receive either NAI 1.2 mg subcutaneous injection on Days 3 (or earlier if ALC <700 cells/µL), Day 14, and potentially Day 21 if ALC remains <1,000 cells/µL, plus standard of care, or standard of care alone. The study will enroll approximately 50 participants (25 per arm) with persistent lymphopenia.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Critical Illness; Septic Shock; Immunosuppression; Lymphopenia
• Intervention / Treatment: Drug: Nogapendekin alfa inbakicept (NAI); Other: Standard of Care (SOC)

Detailed Description

Sepsis is characterized by a biphasic immune response: an initial hyperinflammatory phase followed by a prolonged immunosuppressive phase with persistent lymphopenia. The majority of sepsis deaths (>70%) occur during the immunosuppressive phase rather than the initial hyperinflammatory phase. This acquired immunosuppression correlates with markedly increased 28-day mortality rates exceeding 40% and significantly elevated risk of secondary infections.

This study evaluates NAI, an IL-15 receptor agonist that promotes proliferation and activation of NK cells and CD8+ T cells, as a potential therapy to restore immune function in critically ill adults with sepsis and persistent lymphopenia (ALC <1,000 cells/µL on two consecutive measurements within 72 hours of sepsis diagnosis).

Study Arms:

• Experimental Arm: NAI 1.2 mg subcutaneous injection administered on Days 3 (or earlier than Day 3 if ALC is <700 cells/µL), Day 14, and Day 21 if needed for ALC <1,000 cells/µL, plus institutional standard of care for sepsis
• Control Arm: Institutional standard of care for sepsis alone Standard of care may include antimicrobial therapy, fluid resuscitation, vasopressor support, organ support, and mechanical ventilation as clinically indicated. Treatment will be discontinued if a participant has unacceptable toxicity, withdraws consent, or if the Investigator feels it is no longer in the participant's best interest to continue.

All participants will be followed for 90 days post the first dose of study treatment to capture late adverse events, rehospitalization, or mortality.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tamra Madenwald; Email: Tamra.Madenwald@ImmunityBio.com
• Study Contact Backup: Name: Alex Golway; Phone Number: 516-225-0068; Email: Alex.Golway@ImmunityBio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or older at the time of informed consent
2. Admitted to the ICU with a diagnosis of sepsis as defined by Sepsis-3 criteria: life-threatening organ dysfunction caused by a dysregulated host response to infection, operationalized as a Sequential Organ Failure Assessment (SOFA) score increase of 2 or more points
3. Documented persistent lymphopenia defined as ALC <1,000 cells/µL on at least two consecutive measurements within 72 hours of sepsis diagnosis (measurements must be separated by at least 12 hours)
4. Prior initiation of appropriate antimicrobial therapy per institutional guidelines
5. Ability to obtain written informed consent from the participant or legally authorized representative
6. Agreement to practice effective contraception for female participants of child-bearing potential and non-sterile males (for up to 7 months after completion of therapy)

Exclusion Criteria:

1. Hematologic malignancies including leukemia, lymphoma, and myelodysplastic syndromes
2. Prior CAR-T cell therapy or hematopoietic stem cell transplant (HSCT) within 3 months of screening
3. Active cytokine release syndrome (CRS) at screening
4. Current or recent (within 7 days) use of colony stimulating factors (G-CSF, GM-CSF)
5. Lymphopenia attributable to chemotherapy, radiation therapy, or immunosuppressive medications administered within 30 days prior to screening
6. High-dose immunosuppressive therapy (>0.5 mg/kg prednisone equivalent daily), excluding physiologic replacement and stress-dose hydrocortisone for septic shock
7. Life expectancy less than 24 hours as assessed by the treating physician
8. Active uncontrolled bleeding requiring >2 units of packed red blood cells in the preceding 24 hours
9. Known HIV infection with CD4 count <350 cells/µL and detectable viral load
10. Known active viral hepatitis (hepatitis B or C with detectable viral load)
11. Advanced dementia or other conditions precluding meaningful participation
12. Known hypersensitivity to any component of the investigational products
13. Participation in another interventional trial with an investigational immunomodulatory agent within 30 days prior to screening
14. Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAI + Standard of Care; NAI 1.2 mg subcutaneous injection administered on Days 3 (or earlier if ALC <700 cells/µL), Day 14, and Day 21 if needed for ALC <1,000 cells/µL, plus institutional standard of care for sepsis	Drug: Nogapendekin alfa inbakicept (NAI); IL-15 receptor agonist complex; 1.2 mg subcutaneous injection administered on Days 3 (or earlier if ALC <700 cells/µL), Day 14, and Day 21 if needed for ALC <1,000 cells/µL; Other Names: N-803; ANKTIVA; Nogapendekin alfa-inbakicept; Other: Standard of Care (SOC); Institutional standard of care for sepsis including antimicrobial therapy, fluid resuscitation, vasopressor support, organ support, and mechanical ventilation as clinically indicated
Active Comparator: Standard of Care Alone; Institutional standard of care for sepsis including antimicrobial therapy, fluid resuscitation, vasopressor support, and mechanical ventilation as clinically indicated	Other: Standard of Care (SOC); Institutional standard of care for sepsis including antimicrobial therapy, fluid resuscitation, vasopressor support, organ support, and mechanical ventilation as clinically indicated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day all-cause mortality rate	Proportion of participants who die from any cause within 28 days of randomization	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in absolute lymphocyte count (ALC)	Change in ALC from baseline (Day 1 pre-dose) through Day 28	Baseline through Day 28
ICU re-admission rate	Proportion of participants re-admitted to ICU after discharge by Day 90	Up to Day 90
Secondary infections	Proportion of participants with secondary infections after discharge by Day 90	Up to Day 90
90-day all-cause mortality rate	Proportion of participants who die from any cause within 90 days of randomization	90 days
Safety and tolerability	Incidence and severity of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and Grade ≥3 TEAEs graded per NCI CTCAE v6.0	Through Day 30 after last dose

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): July 6, 2026
• Primary Completion (Estimated): August 3, 2027
• Study Completion (Estimated): October 4, 2027

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 11, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Immunosuppression; ICU; Septic shock; Critical care; Sepsis; N-803; Immune reconstitution; ANKTIVA; Persistent lymphopenia; IL-15 receptor agonist; Nogapendekin alfa inbakicept
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Disease Attributes; Immune System Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Leukocyte Disorders; Hematologic Diseases; Immunologic Deficiency Syndromes; Leukopenia; Shock; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Critical Illness; Sepsis; Lymphopenia; Shock, Septic; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care; ALT-803
• Other Study ID Numbers: ResQ2204-SEPSIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No