Principal Investigator: Neil Kramer, MD, MACR, FACP – Atlantic Health System

Hypothesis / Research Question

To see if addition of anifrolumab to standard of care (mycophenolate mofetil) for class III or IV (with or without concomitant class V) lupus nephritis improves renal response.

Brief Description

Patients with renal biopsy within the 6 months prior to screening showing class III, IV without or without class V lupus nephritis and have a UPCR > 1mg/mg will be randomized 1:1 to receive monthly anifrolumab or placebo, added to MMF 1000 mg BID and followed for 76 weeks. There will also be an open label long term extension study.

Key Criteria

• Inclusion: 1) Active proliferative LN Class III or IV either with or without the presence of Class V  2) Renal biopsy obtained within 6 months prior to signing the informed consent or during screening 3) Urine protein to creatinine ratio > 1mg/mg (113.17 mg/mmole) 4) eGFR > 35 mL/min/1.73 m2 5) Fulfills updated 2019 EULAR/ACR SLE classification criteria 6) No signs of active TB                             
• Exclusion: 1) Pure class V lupus nephritis 2) Primary immunodeficiency, splenectomy or HIV 3) Hepatitis C or active hepatitis B 4) Any history of cancer except cured skin nonmelanoma cancer or cervical cancer in situ. 5) Receipt within the prior 6 months of cyclophosphamide, >2.5 g/day MMF or tacrolimus >4 mg/day for more than 8 weeks.

Contact

  neil.kramer@atlantichealth.org
 (908) 598-7940

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

Principal Investigator: Neil Kramer, MD, MACR, FACP – Atlantic Health System

Hypothesis/Research Question

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 scleroderma and idiopathic inflammatory myopathies.

Brief Description

Dose escalation of NKX019 will utilize a "3+3" design to determine the recommended dose(s) for expansion for enrolling additional participants across indications. The study will evaluate safety and tolerability, preliminary efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity in participants with scleroderma and idiopathic inflammatory myopathies. Participants will receive a cycle consisting of lymphodepletion with fludarabine and cyclophosphamide (Flu/Cy) followed by three doses of NKX019. Participants who are cytopenic may receive a modified lymphodepletion regimen of Cy alone.

Key Criteria

• Inclusion: Age ≥18 and ≤70 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 For subjects on immunosuppressives or immunomodulators (other than corticosteroids), all doses must be stable for ≥ 4 weeks prior to 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: 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 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) Presence of anti-nuclear antibody ≥ 2 x upper limit of normal (ULN) 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 Refractory disease defined as ≥ 6 months failure (or intolerance) to at least 2 immunosuppressive therapies (including glucocorticoids).
• Exclusion: 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 Patients 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) ≤ 40% of predicted at screening (per Investigator or Sponsor judgement) 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.

Contact

 juliana.colecchia@atlantichealth.org
 (908) 522-7350

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 juliana.colecchia@atlantichealth.org
 (908) 522-7350

 More Information