A Study of NKX019, a CD19 CAR NK Cell Therapy, in Subjects With Systemic Lupus Erythematosus

NCT06518668 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: AAAV0505
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective: Safety and tolerability of NKX019, administered after lymphodepletion (LD). Secondary objectives:

• Assess clinical activity of NKX019 in subjects with systemic lupus erythematosus (SLE) with or without active lupus nephritis (LN)
• Characterize pharmacokinetics (PK) of NKX019
• Characterize immunogenicity of NKX019

Conditions

Systemic Lupus Erythematosus

Keywords

CD19; CAR; Allogeneic; NKX019; Cell Therapy; Lupus Nephritis; Systemic lupus erythematosus

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events (AEs)

  This is to measure safety and tolerability of NKX019, administered after lymphodepletion (LD). Adverse events will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, including dose-limiting toxicities (DLTs). A DLT is defined as an AE or clinically significant laboratory abnormality (laboratory abnormalities, including transient \[lasting \< 24 hours\] or isolated out of range values) occurring within 28 days from the first dose that is possibly attributable to NKX019.

  2 years

Secondary Outcomes (5)

• Change from baseline of autoantibody levels

  Up to 2 years after NKX019 infusion

• Change from baseline in hybrid SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score

  Up to 2 years after NKX019 infusion

• Number of participants who achieved renal response

  Up to 2 years after NKX019 infusion

• Maximum concentration (Cmax) of PK in peripheral blood

  Up to 2 years after NKX019 infusion

• Number of subjects with normalized serological activity

  Up to 2 years after NKX019 infusion

Study Arms (1)

NKX019 infusion

EXPERIMENTAL

Subjects with SLE will receive cyclophosphamide LD followed by NKX019.

Biological: NKX019; Drug: Cyclophosphamide LD

Interventions

NKX019 BIOLOGICAL

NKX019 is an investigational allogeneic CD19-Directed CAR NK. NKX019 will be administered at a dose of 1 × 109 CAR NK cells (dose normalized for weight for subjects ≤ 50 kg) administered IV.

Also known as: NKX019 infusion

NKX019 infusion

Cyclophosphamide LD DRUG

Cy dose of 1 g/m2 administered IV over 30 to 60 minutes for the purpose of Lymphodepletion Therapy. Cyclophosphamide will help prepare your body to receive the treatment by decreasing the cells from your immune system to make space for the NKX019 cells. (non-experimental)

Also known as: Cy

NKX019 infusion

Eligibility Criteria

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

You may qualify if:

• Age: 18-65 years old at the time of informed consent
• Signed informed consent form, able to adhere to the study visit schedule, and comply with other requirements of the study as specified in the protocol
• Score of 8 or more points on the Hybrid-SLEDAI with at least 6 points from clinical items and at least one BILAG A or 2 B
• If SLE and LN: Active nephritis Class III or IV with or without Class V using the 2018 International Society of Nephrology and Renal Pathology Society (ISN/RPS) criteria as evidenced on kidney biopsy during screening or within 12 months before study enrollment. Per NIH indices, subjects must have at least activity score ≥ 2 and no more than moderate chronicity index. Subjects must have urinary protein:creatinine ratio (UPCR) ≥ 1.5 g/g or proteinuria ≥ 1.5 g/day, however, subjects must have ≤7g/ day of proteinuria.
• For patients with biopsies older than 6 months we will include an adjudication committee to review clinical data and decide on appropriateness of including the patient (see section 7.3). Additionally, all patients with active LN maximally tolerated doses of renin angiotensin aldosterone system (RAAS) blockade agents, except for patients with contraindications or intolerance to RAAS.
• Women of childbearing potential must have a negative serum pregnancy test at screening and agree to complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study agent until 1 year after the last dose of study agents OR consistent and correct use of acceptable birth control (e.g. levonorgestrel implants, ethinyl estradiol/etonogestrel vaginal ring; injectable progesterone, intrauterine device \[IUD\] with failure rate \< 1% per year, oral contraceptives, double barrier method, transdermal contraceptive patch) OR male partner sterilization with documentation of azoospermia prior to subject's entry into the study.
• Male patients must agree to always use a latex or other synthetic condom during any sexual activity with women of childbearing potential. Male participants must agree to continue to use a condom during the intervention period and for at least 1 year following last treatment with investigational product. Female partners of male participants should be advised to use a highly effective method of contraception during treatment period and at least 12 months following treatment.
• One of the following: positive antinuclear antibodies (ANA) ≥ 1:80 at screening OR positive anti-dsDNA OR positive anti-Smith (anti-Sm) as determined by the local laboratory.
• Refractory SLE defined as having received ≥ 2 prior therapies for SLE (one immunosuppressant and one biologic/advanced therapy) and had an inadequate response to therapy despite being on a therapeutic dose for ≥ 90 days.
• For subjects taking chronic corticosteroids for SLE/LN management, the dose must be stable for ≥ 14 days before screening and cannot exceed 20 mg prednisone/day or equivalent at LD start with planned taper to ≤ 5 mg prednisone by the time of LD start with planned taper to ≤ 5 mg prednisone by the time of the first NKX019 infusion.
• Negative SARS-CoV-2 test.

You may not qualify if:

• Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of \< 45 mL/min/1.73 m2 at screening.
• Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period
• More than 7 g/ day of proteinuria.
• 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 or resting hypoxemia (\< 90% oxygen saturation via pulse oximetry) on room air.
• \>10 pack years of smoking.
• Exacerbation of COPD/asthma requiring systemic steroid therapy within the past 6 months.
• Bone marrow insufficiency unrelated to active SLE (according to Investigator judgment) with white blood cell count \< 1,500/mm3; hemoglobin levels \< 9 g/dL absolute neutrophil count (ANC) \< 1,000/mm3; absolute lymphocyte count \</=500 mm3, or platelet count ≤ 75,000/mm3
• 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 ≤ 45%), or severe cardiac insufficiency

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Anca D Askanase, MD, MPH

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 19, 2024
• First Posted: July 24, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2040
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)