NKX019 for Systemic Sclerosis

Recruiting at 12 trial locations

Overseen By Nkarta Central Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nkarta, Inc.

Disqualifiers: Renal failure, Liver disease, Major cardiac, others

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

Compensation: Varies

Number of Visits: 3

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NKX019, which uses CAR NK cells (a type of immunotherapy) to target a specific protein involved in autoimmune diseases, including systemic sclerosis. The main goal is to determine if this treatment is safe and tolerable for participants. Suitable candidates for this trial have systemic sclerosis with severe skin or lung issues and have not responded well to other treatments. As a Phase 1, Phase 2 trial, it aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications for the NKX019 trial?

The trial information does not specify if you need to stop your current medications. However, it mentions that participants should have an inadequate response or intolerance to certain treatments, which might imply that some medications could be continued. It's best to discuss your specific medications with the trial coordinators.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NKX019, a type of cell therapy using specially designed immune cells, is generally safe and well-tolerated in humans. Early data from previous studies indicated that recipients did not experience severe side effects, such as cytokine release syndrome, a common concern with similar therapies. This suggests NKX019 might be safer than some existing treatments. However, it is important to remember that this therapy remains under investigation. While initial findings are promising, ongoing studies aim to provide a clearer picture of its safety. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for systemic sclerosis?

Unlike the standard treatments for systemic sclerosis, which often include immunosuppressive drugs and therapies targeting inflammation, NKX019 is a CAR NK cell therapy. This innovative approach uses genetically engineered natural killer cells to target and destroy the aberrant cells contributing to the disease. Researchers are excited about NKX019 because it offers a more targeted mechanism of action, potentially reducing disease activity with precision and possibly fewer side effects. This novel therapy could represent a significant advancement in treatment options for patients with systemic sclerosis.

What evidence suggests that NKX019 might be an effective treatment for systemic sclerosis?

Research has shown that NKX019, which uses specially designed immune cells called CAR NK cells, has produced promising results in treating other conditions. Previous studies demonstrated its safety and effectiveness in patients with blood cancers, such as B-cell malignancies. Importantly, patients experienced significant improvement without serious side effects, including a severe immune reaction known as cytokine release syndrome. Although this treatment is new for systemic sclerosis, these findings suggest it could be beneficial. In this trial, participants will receive NKX019, which targets CD19, a protein on certain immune cells, and aims to positively adjust the immune system. ^{1 3 5 6 7}

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 people with certain immune-mediated diseases like systemic sclerosis, inflammatory muscle diseases, and ANCA-associated vasculitis. Participants should meet specific health criteria to be eligible.

Inclusion Criteria

I have tried at least one treatment for SSc without success or could not tolerate it.

My skin is significantly hard due to my condition.

My blood test shows high levels of anti-nuclear antibodies.

Exclusion Criteria

My kidney function is reduced.

I have a history of HIV, Hepatitis B or C, or active tuberculosis.

My heart, immune system, and any past cancers or surgeries do not prevent me from joining.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive a cycle consisting of single-agent lymphodepletion with cyclophosphamide followed by three doses of NKX019

4 weeks

Multiple visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Regular visits at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• NKX019

Trial Overview The study tests NKX019, a type of therapy using modified natural killer cells targeting CD19, along with Cyclophosphamide in patients with immune system-related conditions. It's an early-phase trial to assess safety.

How Is the Trial Designed?

Group I: NKX019 - CAR NK cell therapy Experimental Treatment 3 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

The review highlights the growing interest in CAR-engineered NK cells as a promising alternative to CAR-T cells for cancer treatment, with over 200 clinical trials currently underway since the success of Kymriah® and Yescarta® in 2017.

Initial clinical studies of CAR-NK cells targeting both blood cancers and solid tumors show potential, suggesting that these cells could be used as an 'off the shelf' treatment option, making them more accessible for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-Expressing Natural Killer Cells for Cancer Retargeting. Kloess, S., Kretschmer, A., Stahl, L., et al.[2020]

Patients with systemic sclerosis (SSc) have normal levels of T lymphocytes and natural killer (NK) cells, but their ability to generate immune effector cells, specifically lymphokine-activated killer (LAK) cells, is significantly impaired.

This study, involving 34 SSc patients categorized by disease duration and type, highlights that despite normal cell counts, the poor LAK cell function suggests a compromised immune response to interleukin-2 in SSc patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lymphokine-activated killer cell and natural killer cell activities in patients with systemic sclerosis. Kantor, TV., Whiteside, TL., Friberg, D., et al.[2019]

Transfecting CAR-encoding mRNA into primary natural killer (NK) cells is feasible, with optimal CAR expression achieved after 3 days of IL15 stimulation, resulting in over 80% expression and enhanced targeting of CD19+ cancer cells.

Adaptive NK cells, which have specific markers like NKG2C and CD57, showed superior effectiveness in killing CD19+ tumor cells, indicating that the diversity of NK cell subsets is crucial for optimizing CAR-based cancer immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors. Oei, VYS., Siernicka, M., Graczyk-Jarzynka, A., et al.[2019]

Autologous Hematopoietic Stem Cell Transplantation (AHSCT) shows promise in improving survival and reducing skin and lung fibrosis in patients with rapidly progressive Systemic Sclerosis (SSc), with a study involving 46 patients indicating that certain genetic factors related to HLA-E and HLA-G may influence treatment response.

Higher levels of soluble HLA-E were linked to worse disease severity, while efficient inhibition of Natural Killer (NK) cells, indicated by high expression of HLA-C alleles, correlated with better clinical outcomes after AHSCT, suggesting that immune modulation plays a critical role in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Classical HLA Determinants of the Clinical Response after Autologous Stem Cell Transplantation for Systemic Sclerosis. Boukouaci, W., Lansiaux, P., Lambert, NC., et al.[2022]

Autologous haematopoietic stem cell transplantation (HSCT) significantly improves event-free survival in patients with systemic sclerosis (SSc), with 5, 10, and 15-year survival rates of 78%, 76%, and 66%, respectively, based on a study of 92 patients.

The treatment led to significant improvements in lung function and skin involvement, but treatment-related mortality (TRM) was more common in males and those with lower left ventricular ejection fraction (LVEF) or older age, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive factors for treatment-related mortality and major adverse events after autologous haematopoietic stem cell transplantation for systemic sclerosis: results of a long-term follow-up multicentre study. van Bijnen, S., de Vries-Bouwstra, J., van den Ende, CH., et al.[2020]

In a phase III study comparing two types of stem cell grafts for transplantation, using CD3(+)/CD19(+)-depleted peripheral blood stem cells led to faster repopulation of natural killer (NK) cells, which are crucial for anti-tumor responses after transplantation.

The CD3/19-depleted grafts resulted in a higher proportion of NK cells with activating receptors, enhancing their ability to attack tumors, while the CD34-selected grafts showed slower NK cell development and a predominance of inhibitory receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD3+/CD19+-depleted grafts in HLA-matched allogeneic peripheral blood stem cell transplantation lead to early NK cell cytolytic responses and reduced inhibitory activity of NKG2A. Eissens, DN., Schaap, NP., Preijers, FW., et al.[2020]

A new culture protocol using the aryl hydrocarbon receptor antagonist StemRegenin1 (SR1) allows for the generation of high numbers of functional natural killer (NK) cells from donor hematopoietic stem and progenitor cells, which is crucial for improving outcomes after allogeneic stem cell transplantation (allo-SCT).

The NK cells produced using this method show strong anti-cancer activity against acute myeloid leukemia and multiple myeloma, and their function is not inhibited by cyclosporin A, a common immunosuppressive drug, suggesting that these NK cells could be safely used in post-transplant immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Aryl Hydrocarbon Receptor Antagonist StemRegenin1 Improves In Vitro Generation of Highly Functional Natural Killer Cells from CD34(+) Hematopoietic Stem and Progenitor Cells. Roeven, MW., Thordardottir, S., Kohela, A., et al.[2021]

Allogeneic hematopoietic cell transplantation (HCT) after myeloablative conditioning showed promising results in two patients with severe systemic sclerosis (SSc), with one patient achieving nearly complete resolution of symptoms and improved lung function five years post-transplant.

While one patient experienced significant benefits, the study highlighted the risks of graft-versus-host disease (GVHD) and opportunistic infections, which are common complications associated with allogeneic HCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic marrow transplantation in patients with severe systemic sclerosis: resolution of dermal fibrosis. Nash, RA., McSweeney, PA., Nelson, JL., et al.[2018]

NK cells are directly involved in the rejection of hemopoietic stem cells (HSC) from MHC class I-deficient donors, as shown in a study where purified HSC from these donors failed to engraft in recipient mice with functional NK cells.

The study demonstrated that recipients lacking NK cells successfully accepted HSC from class I-deficient donors, indicating that down-regulation or deletion of specific NK cell subsets can promote tolerance to these cells, highlighting the role of bone marrow-derived elements in NK cell development and tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NK cells play a critical role in the regulation of class I-deficient hemopoietic stem cell engraftment: evidence for NK tolerance correlates with receptor editing. Huang, Y., Rezzoug, F., Xu, H., et al.[2019]

In a study of 50 patients with systemic sclerosis (SSc), researchers found a significant decrease in the absolute number of NK-T cells and T cells expressing g/d TCR, which may contribute to a weakened immune response in these patients.

The study also revealed that lower NK-T cell counts correlated with higher inflammation markers, suggesting that the impairment of these immune cells could play a role in the disease's immunological and inflammatory processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced circulating natural killer T cells and gamma/delta T cells in patients with systemic sclerosis. Riccieri, V., Parisi, G., Spadaro, A., et al.[2005]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06733935

NCT06733935 | A Phase 1/2 Study of NKX019 in Subjects ... The study will evaluate safety and tolerability, preliminary efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity in participants ...

2. cell.com cell.com/cell/fulltext/S0092-8674(24)00701-3

Allogeneic CD19-targeted CAR-T therapy in patients with ... During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients ...

3. nkartatx.com nkartatx.com/pipeline/

Development Pipeline | NKX019 Preliminary data from our Phase 1 hematological malignancy clinical trials supports the safety and tolerability of CAR-NK cells, with no cases of cytokine ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0092867425006257/pdf

An iPSC-derived CD19/BCMA CAR-NK therapy in a patient ... This study reports the first-in-human application of iPSC-derived CD19/BCMA dual-targeting chimeric antigen receptor-natural killer (CAR-NK) ...

5. trials.arthritis.org trials.arthritis.org/trials/NCT06733935

A Phase 1/2 Study of NKX019 in Subjects With Immune ... This is a Phase 1/2, open-label, multi-center, multi-cohort, non-randomized dose escalation and dose expansion basket study to determine the safety and ...

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/559516

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

7. ucihealth.org ucihealth.org/clinical-trials/ascc-24-21

A Phase 1 Study of NKX019 in Subjects with Immune ... This is an open-label, multi-center, multi-cohort, non-randomized Phase 1 study to determine the safety and tolerability of NKX019 ...