DSMB recommendation

The purpose of this study is to assess the efficacy and safety of voclosporin compared to placebo in achieving renal response following 24 weeks of therapy in adolescent and pediatric subjects with active lupus nephritis (LN).

This is a 24 week, dose escalation study of voclosporin in addition to standard of care with mycophenolate mofetil (MMF) and steroids, consisting of 3 treatment periods: Period 1 is double-blind, placebo controlled receiving 15.8 mg twice daily, Period 2 is open-label receiving 23.7 mg twice daily, Period 3 is open-label receiving 15.8 mg twice daily.

Key Inclusion Criteria:

• Previous diagnosis of systemic lupus erythematosus (SLE) as per the 2019 EULAR/ ACR classification criteria.
• Subjects with kidney biopsy confirmed active lupus nephritis.

Exclusion Criteria:

• Estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2 at screening.

• Current or medical history of:

  • Congenital or acquired immunodeficiency.
  • Clinically significant drug or alcohol abuse prior to screening.
  • Malignant neoplasm.
  • Lymphoproliferative disease or previous total lymphoid irradiation.
  • Known severe viral infections within 3 months of screening; or known human immunodeficiency virus infection, or hepatitis B or C virus infection at any time prior to screening.
  • Active tuberculosis (TB) or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid.

• Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period.

• Other known clinically significant active medical conditions, for which the condition or the treatment of the condition may affect the study assessments or outcomes.

• Currently taking or known need for any of the following medications:

  • Immunosuppression biologic agents within 12 weeks prior to randomization, cyclophosphamide, calcineurin inhibitors (CNIs) and live attenuated vaccines, initiation or dose change of ACE inhibitors/ARBs within 4 weeks prior to randomization, IV corticosteroids and IV immunoglobulin within 2 weeks prior to screening, strong CYP3A4/5 inhibitors and inducers within 2 weeks prior to randomization.

Double blind (participant, care provider, investigator and outcome assessor) for period 1 and Open-label for period 2 and period 3