Study of Nogapendekin Alfa Inbakicept and iNKT Cells in Critically Ill Adults With Severe Community-Acquired Pneumonia

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Sepsis; Lymphopenia; Acute Respiratory Distress Syndrome (ARDS); Community-Acquired Pneumonia (CAP); Immunoparalysis
• Intervention / Treatment: Biological: Nogapendekin alfa inbakicept (NAI); Biological: agenT-797

Detailed Description

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:

1. 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.
2. 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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years, adult participants of any gender.

2. 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
   • Confusion or disorientation (new onset mental status changes)
   • Uremia: Blood urea nitrogen (BUN) ≥ 20 mg/dL (7.1 mmol/L)
   • Thrombocytopenia: Platelet count < 100,000/μL
   • Hypothermia: Core temperature < 36.0 °C (96.8 °F)
   • Hypotension requiring aggressive fluid resuscitation
3. Hospital admission with a diagnosis of CAP within 72 hours.
4. Lymphopenia/ Absolute Lymphocyte Count (ALC): ALC < 1,500/μL (not secondary due to chemotherapy).
5. Participants already treated by antibiotics (at least one dose since admission to the ICU).
6. Informed consent: Ability to obtain informed consent from participant or legally authorized representative (given the incapacity of many ICU participants, consent via surrogate/Legally Authorized Representative is allowed per ethics approval).

Exclusion Criteria:

1. Hematologic malignancies (eg, active leukemia and lymphoma, not in remission).
2. Post CAR-T cells therapy or hematopoietic cell transplant for ALL, NHL or Multiple Myeloma less than 3 months prior to enrollment.
3. Participant diagnosed with cytokine release syndrome.
4. Participant receiving colony stimulating factors eg, G-CSF.
5. Clinical history or radiological imaging suggesting aspiration of gastric content.
6. Participant with advanced dementia or prolonged bedridden status.
7. Pregnancy or breastfeeding.
8. 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.
9. Uncontrolled autoimmune or inflammatory disease requiring immunosuppressive therapies (to avoid confounding immune effects or exacerbation).
10. Life expectancy < 24-48 hours or moribund condition despite care (Investigator judgment that participant will not survive long enough to benefit or be evaluated).
11. Active uncontrolled bleeding or intracerebral hemorrhage (cell therapy infusion could transiently affect hemodynamics or coagulation; exclude if such conditions make the intervention risk unjustifiable).
12. Known hypersensitivity to ingredients used in cell product formulation such as DMSO.
13. Treated by antibiotics for a respiratory infection for more than seven days at the time of hospitalization (except if culture and sensitivities determine a resistant organism to the administered antibiotics).
14. Known active Viral Hepatitis A, B, or C.
15. History of human immunodeficiency virus (HIV) with current CD4+ T-cell count < 350 cells/µL and/or a detectable HIV viral load.
16. The Investigator believes that participating in the trial is not in the best interest of the participant, or the Investigator considers the participant unsuitable for enrollment (such as due to unpredictable risks or severe co-morbidities).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm; Participants in this arm receive the investigational treatments: Nogapendekin Alfa Inbakicept (NAI) administered subcutaneously on Day 1 and Day 10, and iNKT cells administered intravenously on Day 3. All participants also receive standard of care (SOC) treatments for severe community-acquired pneumonia, with or without sepsis/ARDS.	Biological: Nogapendekin alfa inbakicept (NAI); NAI is a soluble complex consisting of two protein subunits of a human IL-15 variant (nogapendekin alfa) bound with high affinity to a dimeric human IL 15Rα sushi domain/human IgG1 Fc fusion protein (inbakicept).
Placebo Comparator: Control Arm; Participants in this arm receive placebos matching the investigational treatments: a subcutaneous placebo on Day 1 and Day 10, and an intravenous placebo on Day 3. All participants also receive standard of care (SOC) treatments for severe community-acquired pneumonia, with or without sepsis/ARDS.	Biological: agenT-797; Allogeneic invariant NKT (iNKT) cell therapy - an off-the-shelf cell therapy that can rapidly orchestrate both innate and adaptive immunity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day all-cause mortality	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).	30 days after the last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ALC count	Absolute Lymphocyte Count	From randomization through 28 days following randomization.
Ventilator-Free days (VFD) through Day 28.	The number of days a participant is free from mechanical ventilation.	Through 28 days following randomization.
Number of ICU free days through Day 28.	The number of days a participant is free from being in the Intensive Care Unit.	Through 28 days following randomization.
Number of antibiotic free days through Day 28.	The number of days a participant is free from antibiotic treatment.	Through 28 days following randomization.
Number of days alive and free of organ support through 28 days.	The number of days a participant is alive and does not require organ support.	Through 28 days following randomization.
Time from first administration of study drug to ICU discharge.	The duration from the first dose of study drug until the participant is discharged from the Intensive Care Unit.	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.	The duration from the first dose of study drug until the participant is discharged from the hospital.	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.	The occurrence rate of infections that develop after the start of study treatment.	From randomization through 90 days following randomization.
90-day all-cause mortality.	Death from any cause.	Through 90 days following randomization.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Emergent Adverse Events (TEAEs).	Any adverse event that occurred or worsened after the start of study treatment.	From first study drug administration through 30 days after the last study drug administration.
Serious Adverse Events (SAEs).	Any adverse event that meets predefined serious criteria (e.g., fatal, life-threatening, requires hospitalization).	From first study drug administration through 30 days after the last study drug administration, with related SAEs followed until resolution or stabilization.
Grade ≥3 TEAEs	Treatment emergent adverse events with a severity grade of 3 or higher, based on CTCAE Version 6.0 (or specified grading for CRS/ICANS).	From first study drug administration through 30 days after the last study drug administration.
Safety laboratory tests	Results from various clinical laboratory assessments	At screening, before first study drug administration, on Day 1, 3, 5, 7, 10, then every 3 days until end of ICU stay, at end of ICU stay, and at 28-day follow-up.
Heart rate	Resting heart rate measured by bedside monitor or manual pulse; recorded as the value closest to the scheduled assessment time (beats per minute, bpm).	At screening; pre-dose and 30 min post-dose on Days 1, 3, and 10; daily during hospitalization (up to 10 days); every 4 h for 24 h after Day 3 iNKT infusion; at ICU discharge; and at Day 28 and Day 90 follow-up.
Systolic and diastolic blood pressure	Noninvasive cuff blood pressure or arterial line value if present; record systolic/diastolic (mmHg) nearest scheduled assessment.	At screening; pre-dose and 30 min post-dose on Days 1, 3, and 10; daily during hospitalization (up to 10 days); every 4 h for 24 h after Day 3 iNKT infusion; at ICU discharge; and at Day 28 and Day 90 follow-up.
Respiratory rate	Respiratory rate measured by bedside monitor or counted manually over 60 seconds; record breaths per minute nearest scheduled assessment.	At screening; pre-dose and 30 min post-dose on Days 1, 3, and 10; daily during hospitalization (up to 10 days); every 4 h for 24 h after Day 3 iNKT infusion; at ICU discharge; and at Day 28 and Day 90 follow-up.
Oxygen saturation (SpO2)	Peripheral oxygen saturation by pulse oximetry (%) on current supplemental oxygen; record SpO2 and concurrent FiO2/oxygen delivery method.	At screening; pre-dose and 30 min post-dose on Days 1, 3, and 10; daily during hospitalization (up to 10 days); every 4 h for 24 h after Day 3 iNKT infusion; at ICU discharge; and at Day 28 and Day 90 follow-up.
Body temperature	Core or oral temperature measured per site standard (use same method consistently for a participant); record value in degrees Celsius (°C) nearest scheduled assessment.	At screening; pre-dose and 30 min post-dose on Days 1, 3, and 10; daily during hospitalization (up to 10 days); every 4 h for 24 h after Day 3 iNKT infusion; at ICU discharge; and at Day 28 and Day 90 follow-up.

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.
• Investigators: Study Director: Jayson Garmizo, ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2026
• Primary Completion (Estimated): April 15, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: September 18, 2025
• First Submitted That Met QC Criteria: March 20, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Randomized Controlled Trial; Sepsis; Critical Illness; Phase 3; Immunomodulation; Acute Respiratory Distress Syndrome (ARDS); iNKT Cells; Lymphopenia; Community-Acquired Pneumonia; Severe CAP; ANKTIVA; Nogapendekin Alfa Inbakicept (NAI); Invariant Natural Killer T cells (AgenT-797)
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Disease Attributes; Immune System Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Lung Diseases; Respiration Disorders; Leukocyte Disorders; Hematologic Diseases; Immunologic Deficiency Syndromes; Pneumonia; Leukopenia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Community-Acquired Infections; Respiratory Distress Syndrome; Critical Illness; Sepsis; Lymphopenia; Community-Acquired Pneumonia
• Other Study ID Numbers: ResQ218B-CAP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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