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New treatment option for Systemic Sclerosis
Official title A Phase 1/2 Study of NKX019 in Subjects With Immune-Mediated Diseases (Ntrust-2)
ClinicalTrials.gov ID: NCT06733935
What this study is testing
What is NKX019?
NKX019 is an investigational medicine, being studied as a potential treatment for systemic sclerosis.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 2: a mid-size study of how well it works
- Which group you join is decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 to 75
You may be able to join if
- General
- 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...
- For participants taking corticosteroids, the prednisone (or equivalent) dose must be ≤20 mg/day at 2 weeks prior to Screening and stable for ≥ 14...
You likely can't join 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 (\ 10 pack/year)...
See the full eligibility criteria
Who can join
- General
- 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 SSc
- 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...
- 10 years or less since the first non-Raynaud's sign or symptom
- Inadequate response or intolerance to at least one treatment, including cyclophosphamide, methotrexate, MMF/mycophenolic acid, nintedanib, rituximab, or tocilizumab IIM
- Diagnosis for IIM as per 2017 ACR/EULAR Classification Criteria
- One positive myositis antibody
- Activity defined as manual muscle testing (MMT-8) score \<136/150
- Creatinine kinase or aldolase ≥ 1.5 x ULN and Clinician Global Assessment ≥ 2 cm with at least one of the following:
- Evidence on magnetic resonance imaging (MRI) of active myositis within the last 6 months
- Electromyography (EMG) with active myositis within the last 6 months
- Muscle Biopsy of active myositis within last 6 months
- 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...
- Inadequate response to treatment defined as ≥ 3 months failure (or intolerance) to at least 2 immunosuppressive therapies (including glucocorticoids) AAV:
- Meets the 2022 ACR/EULAR classification criteria for Granulomatosis with Polyangiitis (GPA) (Robson 2022) or Microscopic Polyangiitis (MPA) (Suppiah 2022)
- 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
- Positive test for anti-proteinase-3 (PR3-ANCA) or anti-myeloperoxidase (MPO-ANCA) at screening
- Have at least one "major" item, or at least 3 other items, or at least 2 renal items on the BVAS version 3 RA
- Documented diagnosis of RA, meeting the 2010 ACR/EULAR classification criteria
- Rheumatoid Factor (RF) or Anti-Citrullinated Protein Antibody (ACPA) positive
- CRP \>3 mg/L
- 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:
- At least 1 conventional synthetic DMARD (csDMARD) (eg, methotrexate, leflunomide, sulfasalazine, hydroxychloroquine) AND
- 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...
- Minimum of 6 swollen joint counts (SJCs) and 6 tender joint counts (TJCs) according to joint assessment General
What rules you out
- 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 (\ 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...
- 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 ≤...
- 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 ≤ 40%), or severe cardiac insufficiency
- Prolongation of the QT interval corrected for heart rate (QTc) (Fridericia) interval of \> 480 msec
- 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
- Active bleeding disorders
- 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...
- Pregnancy, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions
- Current infection requiring active systemic anti-infective therapy or recent acute infection requiring systemic therapy within 30 days of planned LD
- History of positive HIV test at screening, Hepatitis B or C positive at screening, active tuberculosis (TB) or latent TB requiring suppressive therapy
- 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
- 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...
- Prior cellular therapy including mesenchymal, CAR-T or CAR-NK cells
- 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...
- 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...
- Gastrointestinal (GI) dysmotility requiring total parenteral nutrition (TPN)
- Renal crisis or Pericardial tamponade within 6 months prior to enrollment
- Current gangrene of a digit IIM Exclusion Criteria:
- Evidence of severe chronic proximal muscle involvement of upper or lower extremities, based on Magnetic Resonance Imaging (MRI) defined as:
- ≥15% fibro-fatty replacement in core muscle groups (including gluteus and vastus musculature), and/or
- ≥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
- MMT-8 of ≤ 80
- 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...
- Generalized severe musculoskeletal or neuro-muscular conditions other than IIM
- Immune-mediated necrotizing myopathy AAV Exclusion Criteria:
- Alveolar hemorrhage requiring invasive pulmonary ventilation support
- Required dialysis or plasma exchange within 12 weeks prior to screening
- 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...
The study team makes the final eligibility decision.
Where it's taking place
- Orange, California, United States
- Gainesville, Florida, United States
- Miami, Florida, United States
- Plantation, Florida, United States
- Chicago, Illinois, United States
- Fairway, Kansas, United States
- Ann Arbor, Michigan, United States
- Minneapolis, Minnesota, United States
- Hackensack, New Jersey, United States
- Summit, New Jersey, United States
- New York, New York, United States
- Stony Brook, New York, United States
- Syracuse, New York, United States
- Dallas, Texas, United States
- Houston, Texas, United States
- Melbourne, Victoria, Australia
- Manati, Puerto Rico
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years to 75 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Orange, California, United States; Gainesville, Florida, United States; Miami, Florida, United States; Plantation, Florida, United States; Chicago, Illinois, United States; Fairway, Kansas, United States and 11 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.