RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-11-04

Study Completion:2028-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06733935

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 70 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age ≥18 and ≤70 2. For participants taking corticosteroids, 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 3. For subjects on immunosuppressives or immunomodulators (other than corticosteroids), all doses must be stable for ≥ 4 weeks prior to Screening 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: 1. 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: * An increase in mRSS of ≥ 3 units * Involvement of 1 new body area with ≥ 2 mRSS units * 2 new body areas with ≥ 1 mRSS unit 2. 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: * Worsening respiratory symptoms * Evidence of progression on HRCT, or * Evidence of absolute decline in FVC ≥ 5% (Raghu et al 2022) 3. Presence of anti-nuclear antibody ≥ 2 x upper limit of normal (ULN) 4. 10 years or less since the first non-Raynaud's sign or symptom 5. Inadequate response or intolerance to at least one treatment, including cyclophosphamide, methotrexate, MMF/mycophenolic acid, nintedanib, rituximab, or tocilizumab 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 5. Refractory disease defined as ≥ 6 months failure (or intolerance) to at least 2 immunosuppressive therapies (including glucocorticoids) 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	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. Patients 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) ≤ 40% of predicted at screening (per Investigator or Sponsor judgement) 8. White blood cell count \< 3,000/mm\^3; hemoglobin levels ≤ 9 g/dL; absolute neutrophil count (ANC) ≤ 2,000/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 16. Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Subjects 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 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 19. Immunosuppressive / immunomodulatory therapies for disease under study within 14 days or 5 half-lives of the drug (whichever is shorter), prior to LD, with notable exceptions a. For those participants on B-cell-depleting or B-cell-modulating drugs (eg, rituximab, belimumab), the participants must have received first dose ≥6 months prior to LD

Inclusion Criteria

Exclusion Criteria

1. Age ≥18 and ≤70
2. For participants taking corticosteroids, 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
3. For subjects on immunosuppressives or immunomodulators (other than corticosteroids), all doses must be stable for ≥ 4 weeks prior to Screening
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:
1. 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:
* An increase in mRSS of ≥ 3 units
* Involvement of 1 new body area with ≥ 2 mRSS units
* 2 new body areas with ≥ 1 mRSS unit
2. 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:
* Worsening respiratory symptoms
* Evidence of progression on HRCT, or
* Evidence of absolute decline in FVC ≥ 5% (Raghu et al 2022)
3. Presence of anti-nuclear antibody ≥ 2 x upper limit of normal (ULN)
4. 10 years or less since the first non-Raynaud's sign or symptom
5. Inadequate response or intolerance to at least one treatment, including cyclophosphamide, methotrexate, MMF/mycophenolic acid, nintedanib, rituximab, or tocilizumab
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
5. Refractory disease defined as ≥ 6 months failure (or intolerance) to at least 2 immunosuppressive therapies (including glucocorticoids)
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

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. Patients 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) ≤ 40% of predicted at screening (per Investigator or Sponsor judgement)
8. White blood cell count \< 3,000/mm\^3; hemoglobin levels ≤ 9 g/dL; absolute neutrophil count (ANC) ≤ 2,000/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
16. Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Subjects 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
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
19. Immunosuppressive / immunomodulatory therapies for disease under study within 14 days or 5 half-lives of the drug (whichever is shorter), prior to LD, with notable exceptions a. For those participants on B-cell-depleting or B-cell-modulating drugs (eg, rituximab, belimumab), the participants must have received first dose ≥6 months prior to LD

Contacts and Locations

Study Contact

Nkarta Central Contact

CONTACT

Only use email

clinicaltrials@nkartatx.com

Principal Investigator

Shawn Rose

STUDY_DIRECTOR

Nkarta, Inc.

Study Locations (Sites)

Nkarta Investigational Site

Orange, California, 92868

United States

Nkarta Investigational Site

Miami, Florida, 33133

United States

Nkarta Investigational Site

Chicago, Illinois, 60612

United States

Nkarta Investigational Site

Fairway, Kansas, 66205

United States

Nkarta Investigational Site

Ann Arbor, Michigan, 48109

United States

Nkarta Investigational Site

Hackensack, New Jersey, 07601

United States

Nkarta Investigational Site

Stony Brook, New York, 11794

United States

Nkarta Investigational Site

Dallas, Texas, 75201

United States

Nkarta Investigational Site

Houston, Texas, 77002

United States

Collaborators and Investigators

Sponsor: Nkarta, Inc.

Shawn Rose, STUDY_DIRECTOR, Nkarta, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-11-04

Study Completion Date2028-10

Study Record Updates

Study Start Date2024-11-04

Study Completion Date2028-10

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Systemic Sclerosis
Idiopathic Inflammatory Myopathies
Antineutrophil Cytoplasmic Antibody-Associated Vasculitis