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

NCT06557265 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NKX019-102
• Study Type: interventional
• Target: 96
• Locations: 2 countries
• Sites: 16

Brief Summary

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).

Conditions

Lupus Nephritis; Primary Membranous Nephropathy

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 dose-limiting toxicities (DLTs) [Safety and Tolerability]

  Incidence of DLTs will be evaluated

  The first 28 days after the first NKX019 dose

Secondary Outcomes (17)

• LN only: Number of participants who achieved Primary Efficacy Renal Response (PERR) (Furie 2020), complete renal response (CRR) and partial renal response (PRR)

  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

  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

• pMN only: Change from baseline in serum albumin

  Up to 2 years after NKX019 infusion

Study Arms (1)

NKX019 - CAR NK cell therapy

EXPERIMENTAL

Phase 1/2: NKX019 plus fludarabine and cyclophosphamide

Drug: NKX019; Drug: Fludarabine, Cyclophosphamide

Interventions

NKX019 DRUG

NKX019 is an investigational allogeneic CD19-Directed CAR NK

NKX019 - CAR NK cell therapy

Fludarabine, Cyclophosphamide DRUG

For Lymphodepletion

NKX019 - CAR NK cell therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤70
• Progression despite maximal tolerated doses of renin-angiotensin system (RAS) blockade agents
• 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
• Negative SARS-CoV-2 test
• For subjects on immunosuppressives or immunomodulators (other than corticosteroids), all doses must be stable for ≥ 4 weeks prior to Screening
• Score of 10 or more points on the American College of Rheumatology (ACR) 2019 classification criteria for SLE
• 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
• 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
• Positive antinuclear antibodies (ANA) ≥ 1:80 OR anti-dsDNA OR anti-Smith (anti-Sm)
• 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
• Evidence of pMN by renal biopsy during screening or within 6 months before screening
• Active renal disease at screening defined by spot UPCR ≥ 3.5 g/g or proteinuria ≥ 3.5 g/day on a 24-hour collection
• Positive anti-PLA2R antibodies
• 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

You may not qualify if:

• eGFR \< 45 ml/min/1.73 m\^2
• Currently requiring renal dialysis or expected to require dialysis during the study period
• Previous solid organ or hematopoietic cell transplant or planned transplant within study treatment period
• Congenital or acquired immunodeficiency resulting in severe infection or those receiving chronic immunoglobulin replacement therapy
• Liver disease or dysfunction, including cirrhosis and/or aspartate aminotransferase, alanine aminotransferase, or bilirubin ≥ 3 times the upper limit of normal
• 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
• 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
• Major cardiac disease, abnormalities, or interventions as defined by, but not limited to:
• Uncontrolled angina or unstable life-threatening arrhythmias
• History of myocardial infarction within 12 weeks prior to the first dose of NKX019
• Any prior coronary artery bypass graft surgery
• ≥ Class III New York Heart Association (NYHA) congestive heart failure (CHF), significantly decreased ejection fraction (EF ≤ 40%), or severe cardiac insufficiency.
• Prolongation of the QT interval corrected for heart rate (QTc) (Fridericia) interval of \> 480 msec
• 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
• Uncontrolled hypertension (systolic blood pressure \> 160mmHg and diastolic \> 90mmHg) despite therapy

Sponsors & Collaborators

• Nkarta, Inc.: lead

Study Sites (16)

Nkarta Investigational Site

Little Rock, Arkansas, 72201, United States

RECRUITING

Nkarta Investigational Site

Gainesville, Florida, 32610, United States

RECRUITING

Nkarta Investigational Site

Miami, Florida, 33133, United States

WITHDRAWN

Nkarta Investigational Site

Plantation, Florida, 33317, United States

RECRUITING

Nkarta Investigational Site

Tampa, Florida, 33602, United States

RECRUITING

Nkarta Investigational Site

Atlanta, Georgia, 30303, United States

RECRUITING

Nkarta Investigational Site

Chicago, Illinois, 60612, United States

RECRUITING

Nkarta Investigational Site

New Orleans, Louisiana, 70112, United States

RECRUITING

Nkarta Investigational Site

Worcester, Massachusetts, 01608, United States

RECRUITING

Nkarta Investigational Site

Ann Arbor, Michigan, 48109, United States

RECRUITING

Nkarta Investigational Site

New York, New York, 10007, United States

RECRUITING

Nkarta Investigational Site

Stony Brook, New York, 11794, United States

RECRUITING

Nkarta Investigational Site

Syracuse, New York, 13202, United States

RECRUITING

Nkarta Investigational Site

Dallas, Texas, 75201, United States

RECRUITING

Nkarta Investigational Site

Houston, Texas, 77002, United States

RECRUITING

Nkarta Investigational Site

Manatí, 00674, Puerto Rico

RECRUITING

Related Links

• The Ntrust-1 Study for Lupus

MeSH Terms

Conditions

Lupus Nephritis

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Nkarta Study Director

  Nkarta, Inc.

  STUDY DIRECTOR

Central Study Contacts

Nkarta Central Contact

CONTACT

Only Use Email; clinicaltrials@nkartatx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: August 16, 2024
• Study Start: June 13, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: March 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (15); PR (1)