Enrollment open for trial testing NKX019 cell therapy in AAV
Study will assess safety, remission potential in 12 patients
Enrollment is now open for a small clinical trial designed to test dose-escalating doses of experimental cell therapy NKX019 in people with ANCA-associated vasculitis (AAV) and other autoimmune disorders.
Called Ntrust-2, the study will assess the therapy’s safety and ability to promote long-term disease remissions in an initial group of up 12 people with AAV, systemic sclerosis, or idiopathic inflammatory myopathy.
The trial, which was cleared by the U.S. Food and Drug Administration earlier this year, will be conducted at multiple centers. Locations have not been announced.
The trial is Nkarta’s second to test NKX019 in people with autoimmune diseases. The first, Ntrust-1 (NCT06557265), is enrolling people with lupus nephritis, a type of kidney inflammation that arises as a complication of systemic lupus erythematosus, at U.S. sites.
“The expansion to these [other] autoimmune indications, in addition to continued execution across our existing clinical trials for lupus nephritis and systemic lupus erythematosus, speaks to the promise of our investigational NK cell therapy, NKX019, to provide a safe and accessible treatment option for people living with autoimmune disease,” Paul J. Hastings, CEO of Nkarta, said in a company press release.
AAV therapy uses NK cells
Preliminary results from Ntrust-1 and Ntrust-2 are expected next year.
AAV is a group of autoimmune diseases characterized by erroneous immune system attacks on the cells lining small blood vessels. AAV, like many autoimmune diseases, is mostly driven by self-reactive antibodies that spur the harmful immune responses against healthy tissue.
B-cells are the type of immune cell that produces both healthy antibodies, which normally help the body fight potential threats, and the self-reactive antibodies that contribute to autoimmune diseases.
NKX019 is designed to eliminate B-cells by using modified natural killer (NK) cells, another type of immune cells, that target B-cells and destroy them. This is expected to potentially slow the harmful immune reactions driven by self-reactive antibodies that mark multiple autoimmune diseases.
To produce NKX019, NK cells are collected from blood of healthy donors. The cells are then genetically engineered to recognize CD19, a protein present at high levels in B-cells’ surface, and to carry IL-15, a signaling molecule that’s meant to prolong NK cells’ survival and activity.
The modified NK cells are then grown into millions and frozen for an off-the-shelf supply of NKX019.
Once thawed, NKX019 is infused into a patient’s bloodstream, where it is expected to destroy B-cells and ultimately ease symptoms of AAV and other B-cell-driven autoimmune diseases.
In the Ntrust-2 trial, people with AAV, systemic sclerosis, or idiopathic inflammatory myopathy will be recruited in parallel treatment groups. Participants will first receive treatment with cyclophosphamide, a chemotherapy medication, to kill B-cells and other immune cells.
NKX019, at a dose of 1 billion or 1.5 billion cells per dose, will then be given on days 0, 3, and 7. Patients will receive no additional immunotherapies, as Nkarta plans to test the efficacy of NKX019 alone to speed the path to regulatory approval.
Nkarta also announced that the FDA cleared the start of an investigator-sponsored Phase 1 trial to test the cell therapy in people with myasthenia gravis, a neuromuscular autoimmune disease also driven by self-reactive antibodies.
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