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

NCT06733935 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Ntrust-2
• Study Type: interventional
• Target: 240
• Locations: 3 countries
• Sites: 17

Brief Summary

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.

Conditions

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Sclerosis; Idiopathic Inflammatory Myopathies; Rheumatoid Arthritis

Keywords

CD19; CAR; Allogeneic; NKX019; Natural Killer Cells; Interleukin-15; IL-15; Cell Therapy; Immunotherapy; Adoptive cell therapy; Scleroderma; Myositis; AAV; Systemic Sclerosis; Idiopathic Inflammatory Myopathies; Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis; Ntrust-2; Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (43)

• For all participants with Interstitial Lung Disease (ILD)

  Up to 2 years after NKX019 infusion

• For all participants with Interstitial Lung Disease (ILD)

  Up to 2 years after NKX019 infusion

• For all participants with Interstitial Lung Disease (ILD)

  Up to 2 years after NKX019 infusion

• For all participants with Interstitial Lung Disease (ILD)

  Up to 2 years after NKX019 infusion

• For all participants with Interstitial Lung Disease (ILD)

  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; Drug: Cyclophosphamide

Interventions

NKX019 DRUG

NKX019 is an investigational allogeneic CD19-Directed CAR NK

NKX019 - CAR NK cell therapy

Fludarabine DRUG

Lymphodepletion

NKX019 - CAR NK cell therapy

Cyclophosphamide DRUG

Lymphodepletion

NKX019 - CAR NK cell therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤75
• Signed informed consent form and ability to adhere to the study visit schedule and comply with other protocol requirements
• 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
• 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
• For participants on immunosuppressives or immunomodulators (other than corticosteroids), all doses must be stable for ≥ 4 weeks prior to Screening
• eGFR as calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of ≥45 mL/min/1.73 m2 at screening
• Meets the 2013 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for SSc
• 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

You may not qualify if:

• eGFR \< 45 ml/min/1.73m2
• 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 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
• Participants with ILD with any of the following:
• Requires supplemental oxygen therapy
• FVC \<45% of predicted
• 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
• 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
• 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

Sponsors & Collaborators

• Nkarta, Inc.: lead

Study Sites (17)

Nkarta Investigational Site

Orange, California, 92868, United States

RECRUITING

Nkarta Investigational Site

Gainesville, Florida, 32601, United States

RECRUITING

Nkarta Investigational Site

Miami, Florida, 33133, United States

WITHDRAWN

Nkarta Investigational Site

Plantation, Florida, 33317, United States

RECRUITING

Nkarta Investigational Site

Chicago, Illinois, 60612, United States

RECRUITING

Nkarta Investigational Site

Fairway, Kansas, 66205, United States

RECRUITING

Nkarta Investigational Site

Ann Arbor, Michigan, 48109, United States

RECRUITING

Nkarta Investigational Site

Minneapolis, Minnesota, 55455, United States

RECRUITING

Nkarta Investigational Site

Hackensack, New Jersey, 07601, United States

RECRUITING

Nkarta Investigational Site

Summit, New Jersey, 07302, 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

Melbourne, Victoria, 3000, Australia

RECRUITING

Nkarta Investigational Site

Manati, 00674, Puerto Rico

RECRUITING

Related Links

• The Ntrust-2 Study for Autoimmune Diseases

MeSH Terms

Conditions

Scleroderma, Systemic; Myositis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Arthritis, Rheumatoid; Scleroderma, Diffuse

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Autoimmune Diseases; Immune System Diseases; Arthritis; Joint Diseases; Rheumatic 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: December 4, 2024
• First Posted: December 13, 2024
• Study Start: November 4, 2024
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: June 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); AU (1); US (15)