Early results from trial testing NKX019 for AAV expected soon
Study still recruiting adults with GPA, MPA in US, Puerto Rico
Preliminary data from a Phase 1 clinical trial testing NKX019, Nkarta’s cell therapy candidate for ANCA-associated vasculitis (AAV) and other autoimmune conditions, are expected in the second half of this year.
That’s according to a mid-year update from the biotechnology company, which is developing the natural killer (NK) cell therapy and sponsoring the trial.
Called Ntrust-2 (NCT06733935), the ongoing study — expected to run through 2028 — is assessing the safety and efficacy of NKX019 in an initial group of up to 36 people with three immune system conditions: AAV, idiopathic inflammatory myopathy, and systemic sclerosis.
The study is still recruiting participants at several sites in the U.S. and one in Puerto Rico. Eligible AAV patients include those with the two most common types of AAV — granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPO).
“We remain focused on the execution of our clinical trials and continue to believe in the differentiated potential of NK cell therapy to address unmet needs in the treatment of autoimmune diseases,” Paul J. Hastings, CEO of Nkarta, said in a company press release.
AAV is an autoimmune disease marked by inflammation and damage to small blood vessels. Most cases are driven by self-reactive antibodies, called ANCAs, that are produced by self-reactive immune B-cells.
NKX019 uses natural killer cells, expected to ease AAV symptoms
The one-time therapy NKX019 uses modified natural killer, or NK, cells, another type of immune cell, to target and eliminate B-cells. This is expected to reduce the production of self-reactive antibodies and ease the symptoms of AAV and other B-cell-driven autoimmune diseases.
The NK cells are collected from healthy donors and modified in the lab to target a protein called CD19 that’s present at the surface of B-cells. The modified cells also harbor a molecule, named IL-15, that’s meant to extend NK cells’ survival and activity.
In the lab, the modified cells are grown into large numbers and frozen, so that NKX019 can be used as an off-the-shelf, or readily available, therapy. The goal is to be able to administer the treatment directly into the patient’s bloodstream whenever needed, without significant delay.
The Ntrust-2 trial, which began enrolling patients late last year, is expected to involve up to 72 adults with the AAV types GPA and MPO, as well as people with systemic sclerosis, also known as scleroderma, and idiopathic inflammatory myopathy. The AAV group is comprised of patients ages 18-65 with hard-to-treat disease who test positive for ANCAs against one of their most common targets, the PR3 or MPO enzymes.
The first part of the study is testing increasing doses of the therapy to identify the optimal dosage to be evaluated in the second part of the study, which will involve a larger number of participants.
Before receiving NKX019, patients will first be administered chemotherapy agents to kill B-cells and other immune cells. Then, the participants will be given a three-dose cycle of NKX019 on days 0, 3, and 7, at a 1 billion or 1.5 billion cells per dose.
No other immunotherapies are allowed during the trial, as testing the efficacy of NKX019 alone can accelerate the path to regulatory approval, the company noted.
Trial assessing safety, tolerability of treatment candidate
The trial’s main goal is to assess the safety and tolerability of NKX019. Secondary goals in the AAV patient group include the percentage of patients achieving disease remission, as assessed with the validated Birmingham Vasculitis Activity Score (BVAS), after up to two years.
Disease remission is defined as a BVAS of zero and a dose of prednisone of up to 5 mg/day. Prednisone is a type of glucocorticoid, a medication commonly used off-label for the treatment of AAV.
Researchers will also assess NKX019’s pharmacological properties and whether participants develop antibodies targeting the delivered NK cells.
Nkarta has launched another Phase 1 trial, called Ntrust-1 (NCT06557265), to test the therapy in people with one of two autoimmune diseases affecting the kidneys, specifically lupus nephritis or primary membranous nephropathy.
Other Phase 1 studies, sponsored by investigators, are evaluating NKX019 in people with other autoimmune diseases, including systemic lupus erythematosus and myasthenia gravis.
According to Nkata, both the Ntrust-1 and Ntrust-2 trials “will assess the safety of NKX019 in people living with autoimmune diseases as well as its ability to enable long-term remissions via a ‘reset’ of the immune system through the elimination of pathogenic [disease-causing] B cells.”
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