First-in-class IL-15 agonist aims to address persistent post-COVID symptoms by enhancing immune clearance and restoring T cell memory.
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ImmunityBio has initiated a phase 2 clinical trial evaluating ANKTIVA (nogapendekin alfa inbakicept-pmln), an interleukin-15 (IL-15) agonist, for patients with long COVID. The trial addresses a major public health challenge, as an estimated one in five American adults with prior SARS-CoV-2 infection continues to experience long COVID symptoms, and no established treatments currently exist.1
The COVID-4.019-Long trial (NCT07123727) is an exploratory, single-arm study enrolling up to 40 participants who meet the World Health Organization’s (WHO) definition of long COVID. The primary endpoint is safety of subcutaneous ANKTIVA, while secondary measures include changes in absolute lymphocyte counts. Exploratory endpoints will assess the drug’s effects on natural killer (NK) cells and CD8+ T cell function, both implicated in persistent viral immune responses.1
According to the WHO, long COVID is defined as the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation.2
ANKTIVA is a first-in-class IL-15 receptor agonist fusion complex designed to enhance NK and CD8+ T cell activity. ImmunityBio founder Patrick Soon-Shiong, MD, explained that viral proteins can persist in tissues months after infection, suggesting that immune modulation, rather than antiviral therapy alone, may be required. By boosting immune clearance and restoring T cell memory, ANKTIVA may offer a novel therapeutic strategy for long COVID.1
The COVID-4.019-Long trial will enroll 40 adults with WHO-defined long COVID, assessing the safety and immune effects of subcutaneous ANKTIVA.
Primary endpoint: safety; secondary: lymphocyte counts; exploratory: NK and CD8+ T cell activity and function.
ANKTIVA’s mechanism suggests immune modulation, not antivirals alone, may be key to treating long COVID, which affects 1 in 5 US adults.
Running from August 2025 through July 2026 at the Chan Soon-Shiong Institute for Medicine in California, the trial will enroll 40 adults who are at least 90 days post–SARS-CoV-2 infection and have had persistent symptoms for ≥60 days that significantly impair daily functioning. Participants will receive 600 μg of ANKTIVA subcutaneously, with close monitoring for adverse events, laboratory abnormalities, and vital sign changes. In addition, researchers will track lymphocyte counts and NK/CD8+ T cell activity to test whether ANKTIVA can correct immune dysregulation and improve quality of life in long COVID.3
Defined as symptoms lasting at least three months after infection, long COVID encompasses more than 200 reported manifestations, including fatigue, cognitive impairment, dyspnea, and cardiovascular complications. Symptoms may fluctuate or recur over time, and while anyone can be affected, vaccination remains the most effective tool for lowering risk and severity.4
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