Enrollment opens in Phase 1 trial of NKX019 cell therapy in gMG
Aim is to test treatment's safety, efficacy; trials in other conditions continue
Enrollment is open in an investigator-initiated clinical trial to evaluate cell therapy NKX019 in people with myasthenia gravis (MG).
Nkarta, the therapy’s developer, made the announcement in a company press release.
Researchers at the University of California, Irvine, and the University of Kansas Medical Center are leading the open-label Phase 1 trial, which was given the go-ahead by the U.S. Food and Drug Administration late last year.
The cell therapy is being tested in separate clinical trials enrolling people with other autoimmune conditions, including lupus, ANCA-associated vasculitis, systemic sclerosis, and idiopathic inflammatory myopathy.
MG is caused when self-reactive antibodies produced by immune B-cells attack proteins involved in nerve-muscle communication, leading to muscle weakness and fatigue. In ocular MG, symptoms are limited to the muscles that control eye and eyelid movements. But in generalized MG, muscle weakness is more widespread, affecting several muscle groups.
CAR therapy uses immune NK cells
NKX019 is a CAR cell therapy that uses immune natural killer (NK) cells from healthy donors. The cells are engineered with a chimeric antigen receptor (CAR), which targets CD19, a protein found on B-cells. On the surface of the modified cells is also a form of interleukin-15, an immune signaling protein, that helps sustain NK cells’ activity.
The CAR cells are then infused into the patient’s bloodstream after lymphodepletion, a procedure used to reduce the number of immune cells and make room for the therapeutic cells. The goal of NKX019 is to reset the immune system by depleting disease-driving B-cells, lowering the levels of self-reactive antibodies, and easing symptoms.
The investigator-initiated trial will assess NKX019’s safety and potential efficacy in people with generalized MG. Participants will receive three doses of the cell therapy on days 0, 3, and 7, after undergoing lymphodepletion with the chemotherapy agent cyclophosphamide.
Goals include assessing the impact of treatment on the levels of related biomarkers, self-reactive antibodies, and immune signaling molecules (cytokines). The therapy’s pharmacokinetics, or how it moves into, through, and out of the body, will also be assessed.
Meanwhile, in clinical trials testing NKX019 in other autoimmune indications, the lymphodepletion regimen has been modified to include a combination of cyclophosphamide and fludarabine, which will be tested alongside the single cyclophosphamide regimen.
“Similar trials have established this combination, and we believe there is value in producing a comparable dataset while still continuing our cyclophosphamide-only regimen for eligible patients,” said Paul J. Hastings, CEO of Nkarta. “This approach has potential to provide data on both regimens, which best positions us to advance NKX019 in the clinic and deliver this potential new treatment to patients with B cell-mediated autoimmune diseases.”
Among those trials is Ntrust-1 (NCT06557265), which is evaluating NKX019’s safety and efficacy in people with lupus nephritis, a common complication of lupus that affects the kidneys, or primary membranous nephropathy.
The new lymphodepletion regimen will also be tested in Ntrust-2 (NCT06733935), a clinical trial testing NKX019 in people with systemic sclerosis, ANCA-associated vasculitis, and idiopathic inflammatory myopathy.
Preliminary data from both studies are expected for the second half of this year, according to Nkarta.
“We remain on track to provide our initial clinical update for the Ntrust-1 and Ntrust-2 studies in the second half of 2025,” Hastings said.
A second investigator-initiated, open-label Phase 1 trial (NCT06518668) is underway to assess the safety and clinical activity of NKX019 in up to six people with systemic lupus erythematosus, regardless of kidney involvement.
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