RecruitingPhase 1 / Phase 2

A Phase 1/2 Study of NKX019 in Subjects With Immune-Mediated Diseases (Ntrust-2)

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 75 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests the safety of NKX019 and how well people can handle it. NKX019 uses immune cells from a donor that are changed to target a protein called CD19. It is for adults with certain autoimmune diseases, in which the immune system attacks the body.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be 18 to 75 years old, sign a consent form, and be able to follow the study schedule and rules.
  • Have a kidney filtering test result (eGFR) of at least 45.
  • If able to become pregnant, have negative pregnancy tests and avoid sex or use approved birth control from 2 weeks before the first dose until 1 year after the last dose.
  • If taking steroids, meet the study’s stable-dose rules and take no more than 20 mg of prednisone daily, or an equal dose of another steroid. Other medicines that change or weaken the immune system must have stable doses for at least 4 weeks before screening.
  • For systemic sclerosis, which can harden skin and affect organs: meet diagnosis rules, have severe or worsening skin disease and/or qualifying lung scarring, and have symptoms other than Raynaud’s for no more than 10 years. At least one listed treatment must not have helped enough or caused side effects you could not tolerate.
  • For inflammatory muscle disease: meet diagnosis rules, have a positive muscle-disease antibody test, and meet muscle weakness and disease activity rules. At least 2 immune-suppressing treatments must have failed after at least 3 months or caused side effects you could not tolerate. Some types have different activity rules.
  • For ANCA-associated vasculitis, which causes swollen blood vessels: have GPA or MPA, a positive PR3-ANCA or MPO-ANCA test, and meet disease activity rules. Disease must have returned or resisted repeated treatment, or need long or repeated courses of unacceptably high steroid doses.
  • For rheumatoid arthritis: meet diagnosis rules, have a positive RF or ACPA blood test, CRP above 3, and at least 6 swollen and 6 tender joints. Meet the study’s rules for poor response after at least 12 weeks of treatment with several types of arthritis medicines.

Who can't join

  • Kidney filtering test result below 45, current or expected dialysis, or certain serious kidney diseases other than the disease being studied. Dialysis is a treatment that filters blood.
  • Past organ or blood-forming cell transplant, or a transplant planned during study treatment.
  • An immune system weakness that causes severe infections, ongoing antibody replacement treatment, or a current or recent infection needing medicine that treats infection throughout the body.
  • Liver disease or poor liver function, including liver scarring or bilirubin at least 3 times the normal upper limit.
  • Certain serious lung problems, including COPD or asthma needing daily steroid pills, low oxygen at rest, or active lung disease with a significant smoking history. Lung scarring needing extra oxygen or with very low breathing test results may also exclude you.
  • Bone marrow problems not caused by the active autoimmune disease that meet the study’s low blood count and recent transfusion rules, or an active bleeding disorder.
  • Certain serious heart or blood vessel problems, such as unstable chest pain or heart rhythms, severe heart failure, any past heart bypass surgery, or a recent heart attack or serious blood clot.
  • Pregnancy, breastfeeding, or not using adequate birth control when able to become pregnant. Another autoimmune condition or its treatment may also exclude you if it could affect study results.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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. For participants taking corticosteroids, 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 5. For participants on immunosuppressives or immunomodulators (other than corticosteroids), all doses must be stable for ≥ 4 weeks prior to Screening 6. eGFR as calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of ≥45 mL/min/1.73 m2 at screening SSc Inclusion Criteria: 1. Meets the 2013 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for SSc 2. Meet criteria a and/or b: a. Severe skin involvement defined as mRSS ≥ 30 or active skin disease defined as mRSS ≥ 15 at screening and one or more of the following within the prior 6 months of screening: i. An increase in mRSS of ≥ 3 units ii. Involvement of 1 new body area with ≥ 2 mRSS units iii. 2 new body areas with ≥ 1 mRSS unit b. Moderate to severe Interstitial Lung Disease (ILD) defined by evidence of ILD on High-resolution computed tomography (HRCT) and FVC \< 70% of predicted or DLCO (hemoglobin or alveolar volume corrected) \< 70% of predicted or ILD on HRCT and progressive ILD meeting at least 2 of the following 3 criteria within the prior 6 months of screening: i. Worsening respiratory symptoms ii. Evidence of progression on HRCT, or iii. Evidence of absolute decline in FVC ≥ 5% 3. 10 years or less since the first non-Raynaud's sign or symptom 4. Inadequate response or intolerance to at least one treatment, including cyclophosphamide, methotrexate, MMF/mycophenolic acid, nintedanib, rituximab, or tocilizumab IIM Inclusion Criteria: 1. Diagnosis for IIM as per 2017 ACR/EULAR Classification Criteria 2. One positive myositis antibody 3. Activity defined as manual muscle testing (MMT-8) score \<136/150 4. Creatinine kinase or aldolase ≥ 1.5 x ULN and Clinician Global Assessment ≥ 2 cm with at least one of the following: 1. Evidence on magnetic resonance imaging (MRI) of active myositis within the last 6 months 2. Electromyography (EMG) with active myositis within the last 6 months 3. Muscle Biopsy of active myositis within last 6 months 4. Global extramuscular activity score ≥2 cm per Clinician global assessment (CGA) using a visual analog scale (VAS) (0-100 mm) Note: Participants with DM or ASyS may be eligible despite CK or aldolase \<1.5 × ULN, provided they have a Clinician Global Assessment ≥2 cm and meet at least one of criteria (a)-(d) above OR have a CDASI score of ≥20. 5. Inadequate response to treatment defined as ≥ 3 months failure (or intolerance) to at least 2 immunosuppressive therapies (including glucocorticoids) AAV: 1. Meets the 2022 ACR/EULAR classification criteria for Granulomatosis with Polyangiitis (GPA) (Robson 2022) or Microscopic Polyangiitis (MPA) (Suppiah 2022) 2. Relapsed or refractory AAV despite repeated treatment with immunosuppressive agents or requiring prolonged and/or repeated courses of unacceptable doses of glucocorticoids to maintain disease control 3. Positive test for anti-proteinase-3 (PR3-ANCA) or anti-myeloperoxidase (MPO-ANCA) at screening 4. Have at least one "major" item, or at least 3 other items, or at least 2 renal items on the BVAS version 3 RA Inclusion Criteria: 1. Documented diagnosis of RA, meeting the 2010 ACR/EULAR classification criteria 2. Rheumatoid Factor (RF) or Anti-Citrullinated Protein Antibody (ACPA) positive 3. CRP \>3 mg/L 4. Inadequate response, defined as failure to achieve a clinically meaningful improvement (eg, ACR50 response or DAS28-low disease activity \[ie, DAS28 \>3.2\]) after at least 12 weeks of therapy with the following: 1. At least 1 conventional synthetic DMARD (csDMARD) (eg, methotrexate, leflunomide, sulfasalazine, hydroxychloroquine) AND 2. Either of the following: i. At least 2 biologic (b) DMARDs (eg, TNF inhibitors, abatacept, anti-IL-6 or anti-IL-6R, rituximab) with distinct mechanisms of action (MoAs) OR ii. At least 1 bDMARD and at least 1 targeted synthetic DMARD (tsDMARD) (eg, JAK inhibitor) AND c. Have failed no more than 3 biologics or tsDMARDs with unique mechanisms of action 5. Minimum of 6 swollen joint counts (SJCs) and 6 tender joint counts (TJCs) according to joint assessment General Exclusion Criteria: 1. eGFR \< 45 ml/min/1.73m2 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 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. Participants with ILD with any of the following: 1. Requires supplemental oxygen therapy 2. FVC \<45% of predicted 3. Diffusing capacity of the lung (DLCO) corrected for alveolar volume (AV) or Hemoglobin (Hgb) ≤ 40% of predicted at screening (per Investigator or Sponsor judgement) i. If the participant has a historical FVC value within the last year that exceeds the 45% threshold, discuss with the Medical Monitor should the Screening FVC be \<45% predicted 8. Bone marrow insufficiency unrelated to active underlying autoimmune disease with white blood cell count \< 3,000/mm\^3; hemoglobin levels ≤ 9 g/dL; absolute neutrophil count (ANC) ≤ 1500/mm\^3; platelet count ≤ 100,000/mm\^3, and blood transfusion within 60 days prior to LD 9. 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 10. Active bleeding disorders 11. 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 12. Pregnancy, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions 13. Current infection requiring active systemic anti-infective therapy or recent acute infection requiring systemic therapy within 30 days of planned LD 14. History of positive HIV test at screening, Hepatitis B or C positive at screening, active tuberculosis (TB) or latent TB requiring suppressive therapy 15. 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 16. 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 17. Prior cellular therapy including mesenchymal, CAR-T or CAR-NK cells 18. 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 evidence of CNS related autoimmune manifestations within 1 year prior to screening SSc Exclusion Criteria: 1. Moderate-to-severe Pulmonary arterial hypertension (PAH) on right heart catheterization requiring PAH specific treatment. Those participants with mild PAH (as defined by the 2022 ECS/ERS Guidelines, \[Humbert 2023\]) well controlled on therapy can be enrolled 2. Gastrointestinal (GI) dysmotility requiring total parenteral nutrition (TPN) 3. Renal crisis or Pericardial tamponade within 6 months prior to enrollment 4. Current gangrene of a digit IIM Exclusion Criteria: 1. Evidence of severe chronic proximal muscle involvement of upper or lower extremities, based on Magnetic Resonance Imaging (MRI) defined as: 1. ≥15% fibro-fatty replacement in core muscle groups (including gluteus and vastus musculature), and/or 2. ≥15% muscle atrophy in these regions Participants will also be excluded if the combined extent of fibro-fatty replacement and muscle atrophy exceeds 30% in aggregate 2. MMT-8 of ≤ 80 3. Findings of muscular inflammation or myopathy due to another cause, such as inclusion body myositis, cancer-associated myositis (myositis diagnosed within 2 years of cancer), amyloid myopathy, muscular dystrophy, metabolic myopathies, or myositis in the context of significant overlap with another systemic IIM rheumatologic disease (overlap myositis), except with Sjögren's syndrome 4. Generalized severe musculoskeletal or neuro-muscular conditions other than IIM 5. Immune-mediated necrotizing myopathy AAV Exclusion Criteria: 1. Alveolar hemorrhage requiring invasive pulmonary ventilation support 2. Required dialysis or plasma exchange within 12 weeks prior to screening 3. Any other known disease that may interfere with the assessments including eosinophilic GPA (Churg-Strauss), anti-glomerular basement membrane, systemic lupus erythematosus, IgA vasculitis (Henoch Schönlein), rheumatoid vasculitis, or cryoglobulinemic vasculitis

Study sites (16)

CA

  • Nkarta Investigational Site · Orange, CA 92868Nkarta Central Contact · Study contactMore trials in Orange

FL

IL

KS

MI

MN

NC

NJ

NY

TX

  • Nkarta Investigational Site · Dallas, TX 75201Nkarta Central Contact · Study contactMore trials in Dallas
  • Nkarta Investigational Site · Houston, TX 77002Nkarta Central Contact · Study contactMore trials in Houston