NAI for Sepsis With Persistent Lymphopenia

Overview

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.

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.