Obe-cel in Severe, Refractory Systemic Lupus Erythematosus (SLE) With Active Lupus Nephritis (LN) (LUMINA)

The purpose of this study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of VX-147 in adult and pediatric participants with apolipoprotein L1 (APOL1)-mediated proteinuric kidney disease.

Inclusion criteria:

• Willing and able to give written informed consent for participation in the study or written informed consent signed by a legal guardian or representative
• Ability and willingness to adhere to protocol's Schedule of Activities and other requirements
• Participants must be 12 to 65 years of age inclusive at the time of signing the informed consent.
• Female Participants: - a female participant is eligible to participate if she is not pregnant or breastfeeding
• Diagnosis of SLE fulfilling the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria for Systemic Lupus Erythematosus.
• Positive for at least 1 of the following autoantibodies: antinuclear antibodies (ANA), or anti-dsDNA or anti-Smith.

• Severe, Active SLE defined as:

  • SLEDAI-2K score of ≥ 8 points AND
  • Severe active LN based on a renal biopsy: Class III, IV or V (V only in combination with class III or IV)
• Refractory SLE defined as failure to previous lines of therapy

Exclusion Criteria:

• Prior treatment at any time with anti-CD19 therapy
• More than 1 acute, severe lupus-related flare during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible
• Significant, likely irreversible organ damage related to SLE (e.g., end-stage renal disease) that in the opinion of the Investigator renders CD19 CAR T cell therapy unlikely to benefit the participant
• History of primary antiphospholipid antibody syndrome
• Active or uncontrolled fungal, bacterial, or viral infection
• History of malignant neoplasms unless disease free for at least 24 months
• History of heart, lung, renal, liver transplant or hematopoietic stem cell transplant

Conditions:
• Lupus