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

Plain English Summary

A Phase 1/2 Study of NKX019 in Subjects With Immune-Mediated Diseases (Ntrust-2) is a Phase 2 clinical trial sponsored by Nkarta, Inc. studying Systemic Sclerosis, Idiopathic Inflammatory Myopathies, Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. This trial tests a new cell therapy called NKX019 for autoimmune diseases. It is for adults with specific conditions like Systemic Sclerosis, Inflammatory Myopathies, or Vasculitis. Participation involves receiving NKX019, which is made from natural killer cells, after a lymphodepletion regimen. Current treatments for these conditions often involve broad immunosuppression; this therapy aims for a more targeted approach. The trial aims to enroll 144 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18-70 can join if they have Systemic Sclerosis, Inflammatory Myopathies, or Vasculitis that hasn't responded well to other treatments. Patients must have specific disease activity markers and meet certain criteria for lung or muscle involvement. Individuals with severe kidney impairment, recent transplants, certain immune deficiencies, or significant heart/lung issues cannot participate. Those with active infections or certain other autoimmune conditions may also be excluded. This trial is studying Systemic Sclerosis, Idiopathic Inflammatory Myopathies, Antineutrophil Cytoplasmic Antibody-Associated Vasculitis, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure the safety of NKX019 by tracking any serious side effects and toxicities that occur within the first month of treatment, helping to understand how well patients tolerate t The specific primary outcome measures are: Incidence of Dose-limiting toxicities (DLTs) [Safety and Tolerability] (The first 28 days after the first NKX019 dose); Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (From the first administration of NKX019 until the last administration of any study treatment + 30 days). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a significant unmet need for patients with severe autoimmune diseases by exploring a novel cell therapy that targets specific immune cells involved in the disease process. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Systemic Sclerosis, Idiopathic Inflammatory Myopathies, Antineutrophil Cytoplasmic Antibody-Associated Vasculitis, where improved treatment options are needed.

Investor Insight

This trial represents an investment in a novel CAR NK cell therapy platform for autoimmune diseases, a large and growing market, with potential for significant differentiation if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if NKX019 is a suitable option for your specific autoimmune condition and if you meet the eligibility criteria. Participation involves regular clinic visits for infusions, blood tests, and monitoring for side effects over a period of time. You will receive a special cell therapy (NKX019) after a preparatory treatment to help the new cells work better. This trial is currently recruiting participants. The trial is being conducted at 15 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 144 participants

Interventions

• DRUG: NKX019 — NKX019 is an investigational allogeneic CD19-Directed CAR NK
• DRUG: Fludarabine — Lymphodepletion
• DRUG: Cyclophosphamide — Lymphodepletion

Primary Outcomes

• Incidence of Dose-limiting toxicities (DLTs) [Safety and Tolerability] (The first 28 days after the first NKX019 dose)
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (From the first administration of NKX019 until the last administration of any study treatment + 30 days)

Secondary Outcomes

• 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 Systemic Sclerosis (SSc) (Up to 2 years after NKX019 infusion)

Full Eligibility Criteria

Inclusion 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

SSc:

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

IIM:

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)

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

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. 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 conditi

Trial Locations

• Nkarta Investigational Site, Orange, California, United States
• Nkarta Investigational Site, Miami, Florida, United States
• Nkarta Investigational Site, Plantation, Florida, United States
• Nkarta Investigational Site, Chicago, Illinois, United States
• Nkarta Investigational Site, Fairway, Kansas, United States
• Nkarta Investigational Site, Ann Arbor, Michigan, United States
• Nkarta Investigational Site, Minneapolis, Minnesota, United States
• Nkarta Investigational Site, Hackensack, New Jersey, United States
• Nkarta Investigational Site, Summit, New Jersey, United States
• Nkarta Investigational Site, New York, New York, United States
• ...and 5 more locations

Frequently Asked Questions

Related Conditions

• Systemic Sclerosis
• Idiopathic Inflammatory Myopathies
• Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
• Autoimmune Diseases
• Rheumatology
• Immunology
• Cell Therapy
• CAR T-cell Therapy
• CAR NK-cell Therapy
• Immunosuppression

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