AB-101 in Combination With B-Cell Depleting mAb in Patients Who Failed Treatment for Class III or IV Lupus Nephritis or Other Forms of Refractory Systemic Lupus Erythematosus
Purpose
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.
Conditions
- Lupus Nephritis - WHO Class III
- Lupus Nephritis - WHO Class IV
- Refractory Systemic Lupus Erythematosus
Eligibility
- Eligible Ages
- Between 18 Years and 99 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
for Lupus Nephritis: - Adult subjects with biopsy proven lupus nephritis Class III or IV either with or without the presence of Class V according to the 2018 Revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria, who failed or did not respond to previous standard of care treatment approaches - A kidney biopsy must be performed < 24 weeks prior to the screening visit or during the screening period. - Eligible subjects must have evidence of active disease on renal biopsy based on the modified NIH Lupus Nephritis activity and chronicity indices. - Eligible subjects must have detectable anti-double stranded DNA antibody titers for enrollment. Inclusion Criteria for Refractory Systemic Lupus Erythematosus: - Diagnosis of SLE according to the 2019 EULAR/ACR Classification Criteria - Total SLE Disease Activity Index (SELENA-SLEDAI score) >8 sat screening - Failed at least 12 weeks of 2 conventional therapies for SLE
Exclusion Criteria
- Known past or current malignancy other than protocol stipulated low grade cancers, or curable cancer in complete response for >2 years - Known clinically significant cardiac disease - Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE - Subjects with known active viral infections or, if with a history of HBV or HCV infections, have a viral load above the institution's limit of quantitation
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Phase 1: Dose confirmation of AB-101 as Monotherapy |
|
|
|
Experimental Phase 1: Dose confirmation of AB-101 plus Rituximab combination |
|
|
|
Experimental Phase 1: Dose confirmation of AB-101 plus Obinutuzumab combination |
|
Recruiting Locations
Birmingham, Alabama 35294
More Details
- Status
- Recruiting
- Sponsor
- Artiva Biotherapeutics, Inc.