CC-97540 in Patients With Antineutrophil Cytoplasmic Antibody-associated Vasculitis

Inclusion Criteria

• •Able to voluntarily provide written informed consent prior to the performance of any study-specific procedures.
• •-≥18 years of age at the time of signing informed consent.
• •Classification as granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) per the American College of Rheumatology (ACR) / European Alliance of Associations for Rheumatology (EULAR) 2022 definitions (Robson et al., 2022, Suppiah et al., 2022) (see Appendix A).
• •Current or historical positive proteinase 3 (PR3) or myeloperoxidase (MPO) antibody testing or a cytoplasmic (cANCA) or perinuclear antineutrophil cytoplasmic antibody (pANCA) immunofluorescence pattern. (Antibodies and immunofluorescence may currently be negative.)
• •Active ANCA-associated vasculitis within 6 weeks of screening presenting as either:
• •Relapsed disease (BVASv3 \> 0 following prior remission) despite standard-of-care treatment per the ACR/Vasculitis Foundation (VF) Guidelines for the Management of ANCA-Associated Vasculitis (Chung et al., 2021), or
• •Refractory disease (persistent BVASv3 positivity) despite standard-of-care treatment per the ACR/VF Guidelines (Chung et al., 2021). Refractory disease is defined as persistent BVASv3 positivity despite at least 6 weeks of appropriate guideline-indicated standard-of-care treatment per the ACR/VF Guidelines for the Management of ANCA-Associated Vasculitis.
• •Appropriate guideline-indicated standard-of-care treatment per the ACR/VF Guidelines for the Management of ANCA-Associated Vasculitis includes:
• •either rituximab or cyclophosphamide for severe disease;
• •or, methotrexate or azathioprine for non-severe disease.
• •-Severe disease activity defined as:
• •1 or more major BVAS/WG criteria or at least 3 minor BVASv3 items (see Appendix B), or
• •1 or more of cutaneous ulceration, retroorbital disease, sinonasal disease with bony or cartilage damage, subglottic stenosis, or renal involvement, or
• •Unanimous expert committee consensus on severity (3/3 agreement).
• •* Left ventricular ejection fraction \> 45%.
• •* Adequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \<2.5 × upper limit of normal (ULN) and direct bilirubin \<1.5 × ULN. Elevation in bilirubin attributable to Gilbert's syndrome is permitted.
• •* Adequate renal function defined by creatinine clearance \>30 ml/min using the Cockcroft-Gault formula. Measured creatinine clearance from a 24-hour urine collection is acceptable if clinically indicated. For select subjects, including those with short stature or low lean muscle mass, alternative calculators to Cockcroft-Gault such as Modification in Diet Renal Disease (MDRD), Chronic Kidney Disease Epidemiology (CKD-EPI), or Cystatin C measurements may be used.
• •* Absolute lymphocyte count of ≥ 300 cells/uL.
• •* Adequate organ function defined as:
• •Hemoglobin ≥ 8 g/dL
• •Platelet count ≥ 75,000/uL
• •* Willingness to adhere to contraceptive requirements. The effects of CC-97540 CAR T cells on the developing human fetus are unknown. Lymphodepleting chemotherapy poses genotoxic, fetotoxic, and infertility risks. For these reasons, women of child-bearing potential and men with partners of childbearing potential must use effective contraception beginning prior to leukapheresis and continuing for at least 12 months after CC-97540 infusion. Due to potential unknown interactions of CC-97540 with hormonal contraception, an additional barrier method should be used if hormonal contraception is chosen. Participants who become pregnant or suspect pregnancy during the study must notify the treating physician immediately.
• •* Ability and willingness to adhere to the study visit schedule and all protocol requirements.