A Phase 1/2 Study of NKX019, a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy, in Subjects With Autoimmune Disease

NCT ID: NCT06557265

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

96 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-13

Study Completion Date

2027-04-30

Brief Summary

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This is an open-label, multi-center, non-randomized, Phase 1/2 study to determine the safety and tolerability of NKX019 (allogeneic CAR NK cells targeting CD19) in participants with active lupus nephritis (LN) or primary membranous nephropathy (pMN).

Detailed Description

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Dose escalation of NKX019 will utilize a "3+3" design to determine the recommended dose(s) for enrolling additional participants across indications. The study will evaluate safety and tolerability, preliminary efficacy, pharmacokinetics, pharmacodynamics in participants with autoimmune diseases. Participants will receive a cycle consisting of lymphodepletion with fludarabine and cyclophosphamide (Flu/Cy), followed by three doses of NKX019. Participants who are cytopenic may receive a modified LD regimen of Cy alone.

Conditions

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Lupus Nephritis Primary Membranous Nephropathy

Keywords

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CD19 CAR Allogeneic NKX019 Interleukin 15 Cell Therapy Immunotherapy Adoptive cell therapy Lupus Nephritis Ntrust-1 LN Primary Membranous Nephropathy pMN

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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NKX019 - CAR NK cell therapy

Phase 1/2: NKX019 plus fludarabine and cyclophosphamide

Group Type EXPERIMENTAL

NKX019

Intervention Type DRUG

NKX019 is an investigational allogeneic CD19-Directed CAR NK

Fludarabine, Cyclophosphamide

Intervention Type DRUG

For Lymphodepletion

Interventions

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NKX019

NKX019 is an investigational allogeneic CD19-Directed CAR NK

Intervention Type DRUG

Fludarabine, Cyclophosphamide

For Lymphodepletion

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age ≥18 and ≤70
2. Progression despite maximal tolerated doses of renin-angiotensin system (RAS) blockade agents
3. For participants taking chronic corticosteroids for management of the disease under study, the prednisone (or equivalent) dose must be ≤40 mg/day at 6 weeks prior to Screening and stable for ≥ 14 days before start of Screening
4. Negative SARS-CoV-2 test
5. For subjects on immunosuppressives or immunomodulators (other than corticosteroids), all doses must be stable for ≥ 4 weeks prior to Screening


1. Score of 10 or more points on the American College of Rheumatology (ACR) 2019 classification criteria for SLE
2. Active biopsy proven lupus nephritis Class III or Class IV with or without Class V using the 2018 International Society of Nephrology and Renal Pathology Society (ISN/RPS) criteria (Bajema 2018) as evidenced on kidney biopsy during screening or within 6 months before screening. For subjects with primarily Class III or Class IV LN, the biopsy must have at least mild to moderate activity score (≥4/24) and no more than moderate chronicity index (≤ 6/12) per NIH indices
3. Active renal disease as defined by urinary protein:creatinine ratio (UPCR) ≥ 1.5 g/g or proteinuria ≥1.5 g/day on a 24-hour collection and ≤ 7 g/day by either measure
4. Positive antinuclear antibodies (ANA) ≥ 1:80 OR anti-dsDNA OR anti-Smith (anti-Sm)
5. Refractory LN defined as having received ≥ 2 prior therapies for LN (immunosuppressant and corticosteroid/or immunomodulatory agent, and corticosteroid at therapeutic range for at least 90 days), and had an inadequate response to therapy despite being on a therapeutic dose for ≥ 90 days


1. Evidence of pMN by renal biopsy during screening or within 6 months before screening
2. Active renal disease at screening defined by spot UPCR ≥ 3.5 g/g or proteinuria ≥ 3.5 g/day on a 24-hour collection
3. Positive anti-PLA2R antibodies
4. Refractory or intolerant to at least one induction therapy for pMN (immunosuppressant and corticosteroid or immunomodulatory agent and/corticosteroid) and defined as not achieving a complete remission after 180 days, or partial remission after 90 days

Exclusion Criteria

1. eGFR \< 45 ml/min/1.73 m\^2
2. Currently requiring renal dialysis or expected to require dialysis during the study period
3. Previous solid organ or hematopoietic cell transplant or planned transplant within study treatment period
4. Congenital or acquired immunodeficiency resulting in severe infection or those receiving chronic immunoglobulin replacement therapy
5. Liver disease or dysfunction, including cirrhosis and/or aspartate aminotransferase, alanine aminotransferase, or bilirubin ≥ 3 times the upper limit of normal
6. Pulmonary comorbidity including chronic obstructive pulmonary disease or asthma requiring daily oral steroids, resting hypoxemia (\<92% oxygen saturation via pulse oximetry) on room air, or significant smoking history (i.e. \>10 pack/year) with active pulmonary disease
7. White blood cell count \< 3,000/mm\^3; hemoglobin levels \< 9 gm/dL absolute neutrophil count \< 2,000/mm\^3; platelet count \< 100,000/mm\^3
8. Major cardiac disease, abnormalities, or interventions as defined by, but not limited to:

1. Uncontrolled angina or unstable life-threatening arrhythmias
2. History of myocardial infarction within 12 weeks prior to the first dose of NKX019
3. Any prior coronary artery bypass graft surgery
4. ≥ Class III New York Heart Association (NYHA) congestive heart failure (CHF), significantly decreased ejection fraction (EF ≤ 40%), or severe cardiac insufficiency.
5. Prolongation of the QT interval corrected for heart rate (QTc) (Fridericia) interval of \> 480 msec
6. Peripheral artery bypass graft surgery, pulmonary embolism, or other ≥ Grade 2 thrombotic or embolic events within 12 weeks prior to the first dose of NKX019
7. Uncontrolled hypertension (systolic blood pressure \> 160mmHg and diastolic \> 90mmHg) despite therapy
9. Active bleeding disorders
10. Any overlapping autoimmune condition for which the condition itself or the treatment of that condition may affect the study assessments or outcomes; clinically significant conditions that could cause a secondary nephropathy; or kidney biopsy-confirmed significant renal disease other than disease under study
11. Pregnancy, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions
12. Current infection requiring active systemic anti-infective therapy or recent acute infection requiring systemic therapy within 30 days of planned LD
13. History of positive HIV antibody or test positive at screening, Hepatitis B or C positive at screening, active tuberculosis (TB) or latent TB requiring suppressive therapy
14. Major surgery within 28 days prior to the first dose of NKX019
15. Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Subjects with cervical dysplasia that is cervical intraepithelial neoplasia but have been treated with conization or loop electrosurgical excision procedure and have had a normal repeat Papanicolaou test are allowed
16. Prior cellular therapy
17. Central nervous system (CNS) comorbidity or any autoimmune disease with CNS involvement within 90 days prior to the first dose of NKX019 as well as active CNS lupus within 1 year prior to screening
18. Any other acute or chronic medical or psychiatric condition, or known laboratory abnormality that, in the Investigator's opinion, is expected to interfere or impact study participation
19. Disease-modifying therapies for disease under study or investigational agents within 14 days or 5 half-lives of the drug (whichever is shorter), prior to LD.

a. For those subjects on B-cell-depleting or -modulating drugs (ie, rituximab, belimumab), the subject must have received first dose ≥ 6 months prior to LD
20. Currently taking or known need for any of the medications prohibited in the study protocol
21. Known hypersensitivity or contraindications to the study treatment including LD; or other components such as human serum albumin or dimethyl sulfoxide


1\. Known clinically active antiphospholipid antibody syndrome (APS); or high-risk profile
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nkarta, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nkarta Study Director

Role: STUDY_DIRECTOR

Nkarta, Inc.

Locations

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Nkarta Investigational Site

Little Rock, Arkansas, United States

Site Status RECRUITING

Nkarta Investigational Site

Gainesville, Florida, United States

Site Status RECRUITING

Nkarta Investigational Site

Miami, Florida, United States

Site Status RECRUITING

Nkarta Investigational Site

Plantation, Florida, United States

Site Status RECRUITING

Nkarta Investigational Site

Atlanta, Georgia, United States

Site Status RECRUITING

Nkarta Investigational Site

Chicago, Illinois, United States

Site Status RECRUITING

Nkarta Investigational Site

New Orleans, Louisiana, United States

Site Status RECRUITING

Nkarta Investigational Site

Worcester, Massachusetts, United States

Site Status RECRUITING

Nkarta Investigational Site

Ann Arbor, Michigan, United States

Site Status RECRUITING

Nkarta Investigational Site

New York, New York, United States

Site Status RECRUITING

Nkarta Investigational Site

Stony Brook, New York, United States

Site Status RECRUITING

Nkarta Investigational Site

Dallas, Texas, United States

Site Status RECRUITING

Nkarta Investigational Site

Houston, Texas, United States

Site Status RECRUITING

Nkarta Investigational Site

Manatí, , Puerto Rico

Site Status RECRUITING

Countries

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United States Puerto Rico

Central Contacts

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Nkarta Central Contact

Role: CONTACT

Phone: Only Use Email

Email: [email protected]

Facility Contacts

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Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Nkarta Central Contact

Role: primary

Related Links

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https://www.ntrust1.com/

The Ntrust-1 Study for Lupus

Other Identifiers

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NKX019-102

Identifier Type: -

Identifier Source: org_study_id