This study will evaluate the safety and activity of AB-101 in combination with rituximab in B-cell associated autoimmune diseases where rituximab is currently FDA approved (e.g., Rheumatoid Arthritis (RA), Pemphigus Vulgaris (PV), Granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA) as a therapeutic, or is recommended (e.g., in Systemic Lupus Erythematosus (SLE) as a cornerstone for disease management.
Males or female subjects, ≥ 18 years of age at the time of signing informed consent.
Ability to understand the requirements of the study.
Willingness to provide written informed consent.
Willingness to comply with the study protocol procedures.
Immunoglobulin replacement therapies (IV or SC)
Plasmapheresis. 8. History of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant, or are due to receive such transplantation.
History of a rheumatologic autoimmune disease other than RA (except secondary Sjögren's)
Significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis, Felty's syndrome)
Single group
AB-101
DrugSubjects in all 4 indications will receive only one cycle of treatment. Subjects with RA, PV or SLE will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2 and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 1000 mg on Day 1 and Day 15 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13 and Day 20 Subjects with GPA and MPA will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2, and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 375 mg/m2 on Day -2, Day 6, Day 13, and Day 20 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13, and Day 20 The first dose of AB-101 should be administered at least 48 hours after the last infusion of the lymphodepletion regimen.
Rituximab
DrugSubjects in all 4 indications will receive only one cycle of treatment. Subjects with RA, PV or SLE will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2 and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 1000 mg on Day 1 and Day 15 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13 and Day 20 Subjects with GPA and MPA will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2, and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 375 mg/m2 on Day -2, Day 6, Day 13, and Day 20 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13, and Day 20 The first dose of AB-101 should be administered at least 48 hours after the last infusion of the lymphodepletion regimen.
Cyclophosphamide
DrugSubjects in all 4 indications will receive only one cycle of treatment. Subjects with RA, PV or SLE will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2 and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 1000 mg on Day 1 and Day 15 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13 and Day 20 Subjects with GPA and MPA will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2, and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 375 mg/m2 on Day -2, Day 6, Day 13, and Day 20 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13, and Day 20 The first dose of AB-101 should be administered at least 48 hours after the last infusion of the lymphodepletion regimen.
Fludarabine
DrugSubjects in all 4 indications will receive only one cycle of treatment. Subjects with RA, PV or SLE will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2 and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 1000 mg on Day 1 and Day 15 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13 and Day 20 Subjects with GPA and MPA will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2, and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 375 mg/m2 on Day -2, Day 6, Day 13, and Day 20 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13, and Day 20 The first dose of AB-101 should be administered at least 48 hours after the last infusion of the lymphodepletion regimen.
Incidence of adverse events and relationship to study drug
We will evaluate the Incidence of adverse events and relationship to study drug
Incidence of Serious Adverse Events (SAE) and causality assessment
We will evaluate the Incidence of adverse events and relationship to study drug
Total hospitalizations, duration of hospitalizations through the course of the study
We will evaluate the Incidence of adverse events and relationship to study drug
RA: Change From Baseline in DAS28 at Week 12 and 24
RA: Change From Baseline in DAS28 at Week 12 and 24
PV: Change from baseline in the Pemphigus Disease Area Index (PDAI) at Week 12 and 24
PV: Change from baseline in the Pemphigus Disease Area Index (PDAI) at Week 12 and 24
GPA / MPA: Change from baseline in the Birmingham Vasculitis Activity Score at Week 12 and 24
GPA / MPA: Change from baseline in the Birmingham Vasculitis Activity Score at Week 12
SLE: Change from baseline in the SLE Disease Activity Index (SLEDAI) at Week 12 and 24
SLE: Change from baseline in the SLE Disease Activity Index (SLEDAI) at Week 12 and 24
Pharmacokinetics and Immunogenicity
Blood samples for pharmacokinetic analysis and immunogenicity will be collected according to the SoA
Patient Reported Outcomes
Patient Reported Outcomes
Pharmacodynamic Biomarkers
The following biomarkers will be measured at baseline and according to the scheduled of assessments. Autoantibodies: ANA, anti-dsDNA, aCL (IgG, IgM, IgA isotypes), anti-Sm, and anti- C1q 2. Serum immunoglobulin isotypes: IgA, IgG, IgM 3. Serum complement (C3, C4) 4. Serum cytokines/chemokines, urinary biomarkers 5. Peripheral B cell subsets, T and NK lymphocytes 6. DSG 1 and DSG 3 autoantibodies
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IRIS Research and Development, LLC
Lead sponsor
Artiva Biotherapeutics, Inc.
Collaborator
