A Phase 1/2 Study of NKX019 in Subjects With Autoimmune Disease (Ntrust-1)

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

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 tolerability of NKX019 (allogeneic CAR NK cells targeting CD19) in participants with autoimmune diseases.

Study Overview

• Status: Recruiting
• Conditions: Lupus Nephritis; Primary Membranous Nephropathy
• Intervention / Treatment: Drug: NKX019; Drug: Fludarabine, Cyclophosphamide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Nkarta Central Contact; Phone Number: Only use email; Email: clinicaltrials@nkartatx.com

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
• Puerto Rico
  • Manati, Puerto Rico, 00674
    • Recruiting
    • Nkarta Investigational Site
    • Contact: Nkarta Central Contact
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72201
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
  • California
    • Tustin, California, United States, 92780
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
    • Miami, Florida, United States, 33133
      • Withdrawn
      • Nkarta Investigational Site
    • Plantation, Florida, United States, 33317
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
    • Tampa, Florida, United States, 33602
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
  • Massachusetts
    • Worcester, Massachusetts, United States, 01608
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
  • New York
    • New York, New York, United States, 10007
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
    • Syracuse, New York, United States, 13202
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
  • Texas
    • Dallas, Texas, United States, 75201
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact
    • Houston, Texas, United States, 77002
      • Recruiting
      • Nkarta Investigational Site
      • Contact: Nkarta Central Contact

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

General Inclusion Criteria:

1. Age ≥18 and ≤75
2. Signed informed consent form and ability to adhere to the study visit schedule and comply with other protocol requirements
3. Women of childbearing potential must have negative pregnancy tests at screening and baseline, and agree to abstinence or acceptable birth control from 2 weeks prior to the first dose through 1 year after the last dose
4. Progression despite maximal tolerated doses of renin-angiotensin system (RAS) blockade agents
5. . For participants taking chronic corticosteroids for management of the disease under study, the prednisone (or equivalent) dose must be ≤20 mg/day at 2 weeks prior to Screening and stable for ≥ 14 days before start of Screening
6. For participants on immunosuppressives or immunomodulators (other than corticosteroids), all doses must be stable for ≥ 4 weeks prior to Screening

LN-specific Inclusion Criteria:

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 without Class V overlap using the 2018 International Society of Nephrology and Renal Pathology Society (ISN/RPS) criteria as evidenced on kidney biopsy during consent or within 6 months before screening. The biopsy must have at least mild to moderate activity score and no more than moderate chronicity index 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. One or more of the following: positive antinuclear antibodies (ANA) ≥ 1:80 at screening OR positive anti-dsDNA OR positive 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

pMN-specific Inclusion Criteria:

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. Presence of primary membranous nephropathy autoantibodies
4. Refractory or intolerant to at least 1 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

General 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. Bone marrow insufficiency unrelated to active underlying autoimmune disease with white blood cell count < 3,000/mm^3; hemoglobin levels < 9 gm/dL absolute neutrophil count < 1500/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 BP > 160mmHg and/or diastolic BP > 90mmHg) despite therapy
9. Active bleeding disorders
10. Any overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes (eg, anti-GBM antibody glomerulonephritis or any condition for additional immunosuppression is indicated); clinically significant conditions that could cause a secondary nephropathy (eg, infections, liver disease, tumors or drugs); or kidney biopsy-confirmed significant renal disease other than disease under study (eg, diabetic nephropathy, hypertensive nephropathy). Overlapping conditions for which the condition or treatment is not expected to affect assessments or outcomes (eg, Sjögren's syndrome, rheumatoid arthritis) are not excluded
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 or any surgery from which the participant has not recovered or has ongoing complications
15. Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Participants 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 including mesenchymal, CAR-T or CAR-NK cells
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. Current participation in another interventional clinical trial

    a. Potential participants can be considered for enrollment after investigational product washout period of 5 half-lives or 30 days, whichever is longer

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

LN-specific Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NKX019 - CAR NK cell therapy; Phase 1/2: NKX019 plus fludarabine and cyclophosphamide	Drug: NKX019; NKX019 is an investigational allogeneic CD19-Directed CAR NK; Drug: Fludarabine, Cyclophosphamide; For Lymphodepletion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicities (DLTs) [Safety and Tolerability]	Incidence of DLTs will be evaluated	The first 28 days after the first NKX019 dose
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Incidence and severity of treatment-emergent adverse events will be evaluated	From the first administration of NKX019 until the last administration of any study treatment + 30 days
Incidence of clinically significant abnormalities in clinical laboratory assessments [Safety and Tolerability]	Incidence of clinically significant laboratory abnormalities will be evaluated	From the first NKX019 dose until the last follow up visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration (Cmax) of NKX019 in peripheral blood		Up to 2 years after NKX019 infusion
Time to Cmax (Tmax) of NKX019 in peripheral blood		Up to 2 years after NKX019 infusion
Area Under the Concentration-time Curve (AUC) of NKX019 in peripheral blood		Up to 2 years after NKX019 infusion
Half-life (t1/2) of NKX019 in peripheral blood		Up to 2 years after NKX019 infusion
Duration of Persistence of NKX019 in peripheral blood		Up to 2 years after NKX019 infusion
pMN only: Change from baseline in serum albumin		Up to 2 years after NKX019 infusion
pMN only: % change from baseline in estimated glomerular filtration rate (eGFR)		Up to 2 years after NKX019 infusion
LN only: Assessment of Lupus Low Disease Activity State (LLDAS) and Definition of Remission in SLE (DORIS) remission over time		Up to 2 years from NKX019 infusion
LN only: Change from baseline in Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) score over time	The SLEDAI-2K score falls between 0 and 105. A higher score represents greater disease activity	Up to 2 years from NKX019 infusion
pMN only: Number of participants who achieved complete remission (CR) and partial remission (PR) and their components (Couser 2017)		Up to 2 years from NKX019 infusion
Evaluation of the effect of treatment on background therapies	Proportion of subjects requiring rescue therapy over time	Up to 2 years after NKX019 infusion
Evaluation of the effect of treatment on background therapies	Proportion of subjects who are steroid free over time	Up to 2 years after NKX019 infusion
Evaluation of the effect of treatment on background therapies	Cumulative corticosteroid dose over time	Up to 2 years after NKX019 infusion
Evaluation of the effect of treatment on background therapies	Proportion of subjects receiving ≤5 mg daily prednisone (or equivalent) over time	Up to 2 years after NKX019 infusion
Evaluation of the effect of treatment on background therapies	Proportion of subjects receiving ≤7.5 mg daily prednisone (or equivalent) over time	Up to 2 years after NKX019 infusion
LN only: Number of participants who achieved Primary Efficacy Renal Response (PERR), complete renal response (CRR) and partial renal response (PRR)	Primary Efficacy Renal Response (PERR), complete renal response (CRR) and partial renal response (PRR) to treatment will be assessed based on European Alliance of Associations for Rheumatology (EULAR)/European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) criteria	Up to 2 years after NKX019 infusion
Assess humoral and cellular immunogenicity over time with validated methods that include: a cell-based flow cytometry assay for anti-NKX019 antibodies and an antigen bead-assay using flow cytometry for detection of anti-HLA antibodies		Up to 2 years after NKX019 infusion

Collaborators and Investigators

• Sponsor: Nkarta, Inc.
• Investigators: Study Director: Nkarta Study Director, Nkarta, Inc.

Publications and helpful links

Helpful Links

• The Ntrust-1 Study for Lupus

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: July 10, 2024
• First Submitted That Met QC Criteria: August 13, 2024
• First Posted (Actual): August 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Immunotherapy; Allogeneic; CD19; CAR; Lupus Nephritis; Adoptive cell therapy; Primary Membranous Nephropathy; LN; Interleukin 15; NKX019; Ntrust-1; pMN
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Skin and Connective Tissue Diseases; Lupus Nephritis; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: NKX019-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No