Phase
Condition
Nephrotic Syndrome
Collagen Vascular Diseases
Idiopathic Membranous Nephropathy
Treatment
Fludarabine, Cyclophosphamide
NKX019
Cyclophosphamide
Clinical Study ID
Ages 18-65 All Genders
Study Summary
Eligibility Criteria
Inclusion
General Inclusion Criteria:
Age ≥18 and ≤65
Progression despite maximal tolerated doses of renin-angiotensin system (RAS)blockade agents
For participants taking chronic corticosteroids for management of the disease understudy, stable dose for ≥ 14 days before the screening visit with planned reductionto ≤ 5 mg prednisone by the time of LD start
Negative SARS-CoV-2 test
LN-specific Inclusion Criteria:
Score of 10 or more points on the American College of Rheumatology (ACR) 2019classification criteria for SLE
Active nephritis Class III, IV, and/or V using the 2018 International Society ofNephrology and Renal Pathology Society (ISN/RPS) criteria (Bajema 2018) as evidencedon kidney biopsy during screening or within 6 months before screening. Per NIHindices, subjects must have at least moderate activity score and no more thanmoderate chronicity index
Active renal disease as defined by urinary protein:creatinine ratio (UPCR) ≥ 1.5 g/gor proteinuria ≥1.5 g/day and ≤ 7 g/day
Positive antinuclear antibodies (ANA) ≥ 1:80 OR anti-dsDNA OR anti-Smith (anti-Sm)
Refractory LN defined as having received ≥ 2 prior therapies for LN
pMN-specific Inclusion Criteria:
Evidence of pMN by renal biopsy during screening or within 6 months before screening
Active renal disease at screening defined by UPCR ≥ 3.5 g/g or proteinuria ≥ 3.5g/day
Positive anti-PLA2R antibodies
Refractory or intolerant to either B cell-depleting agents and/or cyclophosphamideand/or calcineurin inhibitors defined as not achieving a complete remission after 180 days, or partial remission after 90 days
Exclusion
General Exclusion Criteria:
eGFR < 45 ml/min/1.73 m^2
Currently requiring renal dialysis or expected to require dialysis during the studyperiod
Previous solid organ or hematopoietic cell transplant or planned transplant withinstudy treatment period
Congenital or acquired immunodeficiency resulting in severe infection or thosereceiving chronic immunoglobulin replacement therapy
Liver disease or dysfunction, including cirrhosis and/or aspartate aminotransferase,alanine aminotransferase, or bilirubin ≥ 3 times the upper limit of normal
Pulmonary comorbidity including chronic obstructive pulmonary disease or asthmarequiring daily oral steroids, resting hypoxemia (<92% oxygen saturation via pulseoximetry) on room air, or significant smoking history (i.e. >10 pack/year)
White blood cell count < 3,000/mm^3; hemoglobin levels < 9 gm/dL absolute neutrophilcount < 2,000/mm^3; platelet count < 100,000/mm^3
Major cardiac disease, abnormalities, or interventions as defined by, but notlimited to:
Uncontrolled angina or unstable life-threatening arrhythmias
History of myocardial infarction within 12 weeks prior to the first dose ofNKX019
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 cardiacinsufficiency.
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 2thrombotic or embolic events within 12 weeks prior to the first dose of NKX019
Uncontrolled hypertension (systolic blood pressure > 160mmHg and diastolic > 90mmHg) despite therapy
Active bleeding disorders
Any overlapping autoimmune condition for which the condition itself or the treatmentof that condition may affect the study assessments or outcomes; conditions thatcould cause a secondary nephropathy; or kidney biopsy-confirmed significant renaldisease other than disease under study
Pregnancy, breast feeding or, if of childbearing potential, not using adequatecontraceptive precautions
Current infection requiring active systemic anti-infective therapy or recent acuteinfection requiring systemic therapy within 30 days of planned LD
History of positive HIV antibody or test positive at screening, Hepatitis B or Cpositive at screening, active tuberculosis (TB) or latent TB requiring suppressivetherapy
Malignancy within 5 years of screening, with the exception of basal and squamouscell carcinomas treated by complete excision. Subjects with cervical dysplasia thatis cervical intraepithelial neoplasia but have been treated with conization or loopelectrosurgical excision procedure and have had a normal repeat Papanicolaou testare allowed
Prior cellular therapy
Central nervous system (CNS) comorbidity or any autoimmune disease with CNSinvolvement within 90 days prior to the first dose of NKX019 as well as active CNSlupus within 1 year prior to screening
Any other acute or chronic medical or psychiatric condition, or known laboratoryabnormality that, in the Investigator's opinion, is expected to interfere or impactstudy participation
Prior immunosuppressive/immunomodulating therapies, including investigationalagents, within 14 days or 5 half-lives of the drug (whichever is shorter), prior toLD. Note: Prior antibody therapies not allowed within 90 days of LD
Currently taking or known need for any of the medications prohibited in the studyprotocol
Known hypersensitivity or contraindications to the study treatment including LD; orother components such as human serum albumin or dimethyl sulfoxide
LN-specific Exclusion Criteria:
- Known antiphospholipid antibody syndrome (APS); or high-risk profile
Study Design
Study Description
Connect with a study center
Nkarta Investigational Site
Manatí, 00674
Puerto RicoActive - Recruiting
Nkarta Investigational Site
Little Rock, Arkansas 72205
United StatesActive - Recruiting
University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
United StatesActive - Recruiting
Nkarta Investigational Site
Gainesville, Florida 32610
United StatesActive - Recruiting
University of Florida Health Shands Hospital
Gainesville, Florida 32610
United StatesActive - Recruiting
Nkarta Investigational Site
Miami, Florida 33133
United StatesActive - Recruiting
Emory University
Atlanta, Georgia 30322
United StatesActive - Recruiting
Nkarta Investigational Site
Atlanta, Georgia 30322
United StatesActive - Recruiting
Nkarta Investigational Site
Chicago, Illinois 60612
United StatesActive - Recruiting
Nkarta Investigational Site
New Orleans, Louisiana 70018
United StatesActive - Recruiting
Nkarta Investigational Site
Worcester, Massachusetts 01655
United StatesActive - Recruiting
University of Massachusetts
Worcester, Massachusetts 01655
United StatesActive - Recruiting
NYU Langone Health
New York, New York 10016
United StatesActive - Recruiting
Nkarta Investigational Site
New York, New York 10016
United StatesActive - Recruiting
Nkarta Investigational Site
Stony Brook, New York 11794
United StatesActive - Recruiting
Nkarta Investigational Site
Dallas, Texas 75201
United StatesActive - Recruiting
Nkarta Investigational Site
Houston, Texas 77002
United StatesActive - Recruiting
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