NKX019 + Cyclophosphamide for Lupus Nephritis

Recruiting at 18 trial locations

Overseen By Nkarta Central Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nkarta, Inc.

Must be taking: Renin-angiotensin system blockers

Disqualifiers: Renal dialysis, Liver disease, COPD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy called NKX019 (allogeneic CAR NK cells targeting CD19) for individuals with lupus nephritis or primary membranous nephropathy. The main goal is to determine the treatment's safety and tolerability. Participants should have active kidney disease that hasn't improved with other treatments. Those with lupus nephritis need a score of 10 or higher on a specific lupus scale, while those with primary membranous nephropathy must have certain positive antibodies. This trial may suit individuals whose previous treatments haven't fully worked and who have active kidney involvement. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that NKX019 is likely to be safe for humans?

Research has shown that NKX019, a therapy using specially designed natural killer cells, has been tested for safety in conditions like lupus nephritis and systemic lupus erythematosus. These studies suggest it targets and removes certain immune cells without causing severe side effects. Most patients in these studies tolerated the treatment well. Some experienced mild to moderate reactions, such as tiredness or fever, but serious problems were rare.

As this is a Phase 1 trial, the primary goal is to assess the treatment's safety. Phase 1 trials typically mark the first time a new treatment is tested in humans, so safety is monitored very closely. While early results are encouraging, further research is needed to fully understand any long-term effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus nephritis?

Researchers are excited about NKX019, especially for lupus nephritis, because it represents a novel approach compared to traditional immunosuppressive treatments like corticosteroids and cyclophosphamide alone. Unlike these standard treatments, NKX019 uses CAR NK cell therapy, which harnesses the power of modified natural killer (NK) cells to precisely target and eliminate disease-causing cells. This innovative mechanism offers the potential for more targeted therapy with possibly fewer side effects. Additionally, combining NKX019 with cyclophosphamide and fludarabine might enhance treatment efficacy, paving the way for more effective management of lupus nephritis.

What evidence suggests that NKX019 might be an effective treatment for lupus nephritis?

Research has shown that NKX019, a type of cell therapy, could help treat lupus nephritis (LN) by targeting a protein called CD19, which plays a role in the immune system. This treatment uses natural killer (NK) cells from healthy donors, modified to attack cells with CD19. Early results suggest this method might reduce the effects of systemic lupus erythematosus (SLE), a condition similar to LN. Some patients with SLE have responded well, indicating possible benefits for those with LN. Although more research is needed, these early findings offer hope for this treatment's success. Participants in this trial will receive NKX019 in combination with fludarabine and cyclophosphamide. ^{2 5 6 7 8}

Who Is on the Research Team?

Nkarta Study Director

Principal Investigator

Nkarta, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with active lupus nephritis, a type of kidney inflammation due to autoimmune disease. Participants must meet certain health standards but specific inclusion and exclusion criteria are not listed.

Inclusion Criteria

Must have a negative SARS-CoV-2 test

I have lupus nephritis and have tried at least 2 treatments that didn't work.

My kidney biopsy shows active Class III or IV lupus nephritis.

Exclusion Criteria

I do not have HIV, Hepatitis B or C, active tuberculosis, antiphospholipid antibody syndrome, or a high-risk profile.

My kidney function is reduced, with an eGFR of 45 ml/min/m2 or lower.

I have liver disease or abnormal liver tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive single-agent lymphodepletion with cyclophosphamide

1 week

Treatment

Participants receive a three-dose cycle of NKX019

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term follow-up

Participants are monitored for changes in SLEDAI-2K score and renal response

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• NKX019

Trial Overview The study tests NKX019, a therapy involving immune cells (CAR NK) designed to target CD19, in combination with Cyclophosphamide, a chemotherapy drug. It's an early-phase trial to assess safety and how well patients tolerate the treatment.

How Is the Trial Designed?

Group I: NKX019 - CAR NK cell therapy Experimental Treatment 2 Interventions

Phase 1/2: NKX019 plus fludarabine and cyclophosphamide

Who Is Running the Clinical Trial?

Nkarta, Inc.

Lead Sponsor

Trials

4

Recruited

300+

Published Research Related to This Trial

High-dose corticosteroids are the standard initial treatment for severe inflammation in lupus nephritis, but long-term management often requires additional therapies to address underlying immune system issues.

New treatment options for lupus nephritis include novel immunosuppressive agents and combination therapies, which may improve efficacy and reduce toxicity compared to traditional treatments like cyclophosphamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in the treatment of proliferative lupus nephritis. Balow, JE., Austin, HA.[2019]

Low-dose cyclophosphamide (LCYC) is an effective induction therapy for lupus nephritis, showing similar response rates to mycophenolate mofetil (MMF) and better than high-dose cyclophosphamide (HCYC) based on a meta-analysis of 11 randomized controlled trials involving 1212 patients.

LCYC also has the highest probability of reducing the risk of serious infections compared to MMF and HCYC, making it a safer option for patients undergoing treatment for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of low-dose and high-dose cyclophosphamide as induction therapy for lupus nephritis: a network meta-analysis. Bae, SC., Lee, YH.[2020]

In a study involving (NZB x NZW)F(1) (B/W) mice, the combination of cyclophosphamide (CTX) and CTLA4Ig significantly reduced proteinuria and improved survival rates in mice with advanced renal disease, outperforming either treatment alone.

This combination therapy not only delayed the onset of kidney issues in mice with mild disease but also achieved a remarkable reversal of proteinuria in 71% of mice with advanced nephritis, marking a significant advancement in treatment for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutting edge: reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide. Daikh, DI., Wofsy, D.[2019]

In patients with systemic lupus erythematosus (SLE), there is an increased expression of the NKG2D ligand MICA in the kidneys, indicating a potential role of NK cells in the disease's progression.

Murine models of SLE showed that NK cells in the kidneys have a more mature and activated phenotype during lupus nephritis, suggesting that these cells may contribute to the immunopathogenesis of SLE and could be targeted for therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NKG2D ligand overexpression in lupus nephritis correlates with increased NK cell activity and differentiation in kidneys but not in the periphery. Spada, R., Rojas, JM., Pérez-Yagüe, S., et al.[2019]

Current treatments for lupus nephritis, like corticosteroids and cyclophosphamide, are effective but come with significant side effects, highlighting the need for safer, targeted therapies.

New therapeutic strategies are being developed to specifically interrupt the disease process, such as blocking co-stimulatory molecules and targeting cytokines, which could lead to more effective and less toxic treatments for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel approaches in the treatment of lupus nephritis. Illei, GG., Czirják, L.[2019]

In patients with systemic lupus erythematosus (SLE), there is a significant reduction in the levels and cytotoxicity of natural killer (NK) cells compared to healthy controls, particularly in those with lupus nephritis and thrombocytopenia.

The study found that the differentiation of hematopoietic stem cells (HSCs) into NK cells is impaired in SLE patients, which may contribute to the overall immune system dysregulation associated with the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythematosus. Park, YW., Kee, SJ., Cho, YN., et al.[2009]

High-dose cyclophosphamide (HDCyC) and rituximab were found to be the most effective treatments for lupus nephritis (LN) in a study of 222 patients, with renal response rates of 90.3% and 90.9%, respectively.

Rituximab showed particular effectiveness in patients with relapsing disease, achieving a 100% renal response rate, while the study also noted that high-dose cyclophosphamide was associated with a higher incidence of infections compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclophosphamide Versus Mycophenolate Versus Rituximab in Lupus Nephritis Remission Induction: A Historical Head-to-Head Comparative Study. Goswami, RP., Sircar, G., Sit, H., et al.[2022]

This study is the first to characterize natural killer (NK) cells in kidney biopsies of patients with lupus nephritis (LN), revealing their presence in the kidney interstitium and peri-glomerular areas, but rarely in glomeruli.

Among the 12 SLE patients analyzed, NK cell numbers were reduced in four out of five patients after immunosuppressive therapy, indicating a potential link between NK cell activity and disease status, although the small sample size limits definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kidney infiltrating NK cells and NK-like T-cells in lupus nephritis: presence, localization, and the effect of immunosuppressive treatment. Scheffschick, A., Fuchs, S., Malmström, V., et al.[2023]

Patients with active systemic lupus erythematosus (SLE) show a decreased absolute count of natural killer (NK) cells, but their relative frequencies remain unchanged, indicating a potential alteration in NK cell dynamics during disease activity.

NK cells from SLE patients exhibit unique phenotypic changes and lower cytotoxicity, yet they can produce significant amounts of interferon-gamma (IFNγ), which may disrupt the balance between innate and adaptive immunity in SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenotype and function of natural killer cells in systemic lupus erythematosus: excess interferon-γ production in patients with active disease. Hervier, B., Beziat, V., Haroche, J., et al.[2017]

In a study involving 191 patients with systemic lupus erythematosus (SLE) and other autoimmune diseases, 23% of SLE patients had autoantibodies against killer immunoglobulin-like receptors (KIRs), which are crucial for NK cell function.

These anti-KIR autoantibodies were linked to reduced NK cell activity, increased disease activity, and a higher risk of developing lupus nephritis, suggesting that impaired NK cell function may contribute to disease severity in SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autoantibodies to Killer Cell Immunoglobulin-Like Receptors in Patients With Systemic Lupus Erythematosus Induce Natural Killer Cell Hyporesponsiveness. Segerberg, F., Lundtoft, C., Reid, S., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06518668?cond=Lupus%20Erythematosus&aggFilters=status:rec&country=United%20States&locStr=United%20States&viewType=Table&rank=5

NCT06518668 | A Study of NKX019, a CD19 CAR NK Cell ... This is to measure/assess clinical activity of NKX019 in subjects with systemic lupus erythematosus (SLE) with or without active lupus nephritis (LN). Anti- ...

2. ir.nkartatx.com ir.nkartatx.com/news-releases/news-release-details/nkarta-announces-initiation-investigator-sponsored-clinical

Nkarta Announces Initiation of Investigator-Sponsored ... In June 2024, Nkarta announced the initiation of Ntrust-1, its Phase 1 clinical trial of NKX019 in patients with lupus nephritis (LN). The ...

3. lupus.org lupus.org/news/investigational-therapy-nkx019-for-lupus-nephritis-treatment-begins-screening-trial

Investigational Therapy NKX019 for Lupus Nephritis ... NKX019 is engineered by collecting NK cells from healthy donor blood and modified with a CAR designed to target CD19, a protein found on the ...

4. conferences.medicom-publishers.com conferences.medicom-publishers.com/specialisation/rheumatology/acr-2024/allogeneic-cd19-targeting-car-nk-cell-therapy-for-sle/

Allogeneic CD19-targeting CAR NK-cell therapy for SLE Data from an ongoing clinical trial suggests that allogeneic CD19-targeting chimeric antigen receptor (CAR) natural killer (NK)-cell therapy for systemic lupus ...

5. trial.medpath.com trial.medpath.com/clinical-trial/fa87e79095f3b929/nkx019-cd19-car-nk-cell-therapy-autoimmune-disease

NKX019, Intravenous Allogeneic Chimeric Antigen Receptor ... This is an open-label, multi-center, non-randomized Phase 1 study to determine the safety and tolerability of NKX019 (allogeneic CAR NK cells targeting ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2025-07265

NKX019, Intravenous Allogeneic Chimeric Antigen ... This is an open-label, multi-center, non-randomized Phase 1 study to determine the safety and tolerability of NKX019 (allogeneic CAR NK cells targeting ...

7. ir.nkartatx.com ir.nkartatx.com/node/9266/pdf

Nkarta Initiates Clinical Trial of NKX019 in Lupus Nephritis ... NKX019 is an allogeneic, off-the-shelf, chimeric antigen receptor (CAR) NK-cell therapy candidate engineered to deplete CD19-positive cells in B ...

8. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper212347.html

Paper: A Phase 1 Study of NKX019, an Allogeneic ... Recently, CD19-directed chimeric antigen receptor (CAR) T-cell therapy has shown promising early results in patients with SLE and lupus nephritis (LN) via ...