Nkarta cell therapy trial may soon offer outpatient treatment option in AAV
FDA agrees to protocol update that may expand patient access to NKX019
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Treatment with Nkarta’s lead candidate NKX019 in two ongoing, early-phase clinical trials may soon be available in outpatient settings — potentially expanding access for people with ANCA-associated vasculitis (AAV) and other autoimmune disorders — thanks to a new regulatory nod.
The company announced it has reached an agreement with the U.S. Food and Drug Administration (FDA) on a set of key changes to the protocols for its ongoing Phase 1/2 trials Ntrust-1 (NCT06557265) and Ntrust-2 (NCT06733935). One change is the addition of an option for outpatient dosing of NKX019.
Under the amended protocols, patients receiving NKX019 will no longer require overnight monitoring, according to the developer. Instead, observation time will be reduced from 24 hours to approximately two hours after dosing.
Once approved by institutional review boards (IRBs), which are independent committees that oversee patient safety in clinical trials, the therapy could be administered in outpatient settings, including community research sites and rheumatology clinics, rather than being limited to specialized centers, per Nkarta. The shift is expected to reduce the burden on patients while expanding access to treatment, according to a company press release announcing the protocol changes.
“We are pleased to reach agreement with the FDA on several protocol enhancements that will meaningfully improve the patient and trial site experience while supporting continued advancement of our NKX019 clinical program,” said Paul J. Hastings, CEO of Nkarta. “Reaching agreement with the FDA on outpatient dosing — reducing the need for patient monitoring from 24 hours to 2 hours — will reduce patient burden and expand access.”
Hastings added that the changes “will also allow us to partner with community rheumatology centers, better positioning us to execute efficiently across our clinical program while expanding access to next-generation innovation to people from all walks of life, putting patients first.”
AAV and other autoimmune disorders occur when the body’s immune system mistakenly attacks its own healthy cells and tissues. Such attacks are driven by abnormal immune B-cells that produce self-reactive antibodies.
NKX019 is Nkarta’s ready-to-use cell therapy candidate
NKX019 is a cell therapy designed to target and eliminate such abnormal B-cells. Unlike conventional cell therapies that must be made individually for each patient in a time-consuming and costly process, NKX019 can be given off-the-shelf, meaning it is manufactured in advance and readily available for use.
Treatment involves collecting natural killer (NK) cells, a type of immune cell, from the blood of a healthy donor. These cells are then modified in the lab to produce a chimeric antigen receptor, or CAR, that recognizes CD19, a protein found at high levels on the surface of B-cells. They are also engineered to carry IL-15, an immune signaling molecule that helps NK cells survive and remain active longer. This allows the therapy to be administered without requiring additional immune molecules to enhance its activity.
The modified NK cells are then grown into large numbers and stored frozen. Once thawed and infused into a patient’s bloodstream, they are expected to destroy B-cells and reduce the production of disease-driving antibodies, easing symptoms of AAV and other B-cell-mediated autoimmune diseases.
The cell therapy is now being tested in two trials underway at study sites in the U.S. and its territory Puerto Rico.
Ntrust-2 trial testing treatment’s safety, effectiveness in AAV
Ntrust-1 is testing the therapy’s safety and effectiveness in an estimated 96 adults with treatment-resistant lupus nephritis, a type of kidney inflammation that arises as a complication of the B-cell-mediated autoimmune disease lupus. The trial is recruiting participants ages 18 to 70 at multiple sites in the U.S. and at a single site in Puerto Rico.
The Ntrust-2 trial, which began enrolling patients in 2024, is evaluating the safety and effectiveness of NKX019 in people with AAV, systemic sclerosis, also known as scleroderma, or idiopathic inflammatory myopathy. In AVV, the therapy is specifically being tested in people with difficult-to-treat granulomatosis with polyangiitis or microscopic polyangiitis — the two most common types of AAV — who test positive for ANCAs against the PR3 or MPO proteins, the main targets of AAV-driving antibodies.
Under the amended protocols, the study will also include an additional group of people with rheumatoid arthritis. The trial is actively enrolling patients ages 18 to 70 at sites in several U.S. states and in Puerto Rico and is expected to involve about 144 adults.
Our agreement with the FDA expands who we can treat — and how — in clinical trials [of NKX019].
In both trials, participants will receive a three-dose cycle of NKX019 on days 0, 3, and 7, following treatment with the chemotherapy drugs fludarabine and cyclophosphamide or cyclophosphamide alone. These medications are used to destroy existing immune cells, including B-cells and NK cells, to make room for infused therapy.
No additional immunotherapies will be given, allowing NKX019 to be evaluated as a single agent and potentially streamlining its development, Nkarta said.
The initial part of both studies is testing increasing doses of NKX019 in small groups of patients to help determine the safest and most effective dose before enrolling additional participants. Early data from both trial are expected later this year.
The protocol updates also introduce the option to redose patients in both trials, if needed, to help optimize treatment responses.
“Our agreement with the FDA expands who we can treat — and how — in clinical trials,” Hastings said. ” When the amended protocol completes IRB review and is finalized, we can begin enrolling patients with rheumatoid arthritis in Ntrust-2. We’re also gaining the flexibility to re-dose participants in both studies, if needed, as an option to help optimize treatment responses in individual patients.”
