Lupus Nephritis - WHO Class III, Lupus Nephritis - WHO Class IV, Refractory Systemic Lupus Erythematosus, SLE
Conditions
Keywords
SLE, Lupus, Lupus Nephritis, AlloNK
Brief summary
AB-101 (also known as AlloNK) is an off-the shelf, allogeneic cell product made of natural killer cells, also called NK cells. White blood cells are part of the immune system and NK cells are a type of white blood cell that is known to enhance the effect of monoclonal antibody therapies. This clinical trial will enroll adult patients with lupus nephritis Class III or IV either with or without the presence of Class V who relapsed or did not respond to previous standard of care treatment approaches, or other forms of refractory systemic lupus erythematosus. The primary objective is to assess the safety, tolerability and preliminary activity of AB-101 plus a B-cell depleting mAb (e.g., rituximab, obinutuzumab) after cyclophosphamide and fludarabine in adult subjects with relapsed/refractory lupus nephritis Class III or IV, with or without the presence of Class V, or other forms of refractory systemic lupus erythematosus. Patients will be assigned to receive either AB-101 alone as monotherapy or in combination with a B-cell depleting mAb (e.g., rituximab, obinutuzumab). All patients will receive at least 1 treatment cycle of AB-101, followed by scheduled assessments of overall health and response status. Patients may receive up to 2 cycles of treatment spaced 24 weeks apart.
Interventions
DRUGAB-101
NK Cell Therapy
DRUGCyclophosphamide
Lymphodepleting chemotherapy
DRUGFludarabine
Lymphodepleting chemotherapy
DRUGRituximab
Anti-CD20 antibody therapy
DRUGObinutuzumab
Anti-CD20 antibody therapy
Sponsors
Artiva Biotherapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for all subjects (Lupus Nephritis or SLE) * Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria * Subjects must have had an inadequate response with at least two prior lines of standard of care (SoC) treatment. Inclusion Criteria for LN: * Adult subjects with lupus nephritis Class III or IV (with or without the presence of Class V) * Evidence of active disease on renal biopsy. * All subjects are required to receive adequate concomitant antihypertensive and antiproteinuric therapy with blockade of the renin-angiotensin system Inclusion Criteria for SLE: * Total systemic lupus erythematosus disease activity index (SLEDAI-2K score) ≥ 8, and clinical SLEDAI-2K ≥ 4. * British Isles Lupus Assessment Group 2004 (BILAG-2004) activity score of A in ≥ 1 organ, or a BILAG-2004 activity score of B in ≥ 2 organs. * Subjects have failed at least two conventional therapies
Exclusion criteria
* Known past or current malignancy * Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE * Subjects with known active viral infections * Severe active CNS Lupus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events | From the time of consent through 104 weeks after initiation of study treatment | Incidence, severity and causality of adverse events and serious adverse events |
| AB-101 Clinical Activity | From the time of first dose through 104 weeks after initiation of study treatment | Determined by Overall Response Rate in subjects with lupus nephritis and refractory systemic lupus erythematosus |
Countries
United States
Outcome results
None listed