PRESERVE: LUPKYNIS in Combination With Belimumab, Obinutuzumab or Anifrolumab in Patients With Lupus Nephritis

PRESERVE: A Multi-Center Phase 4 Study of the Efficacy and Safety of LUPKYNIS in Combination With Belimumab, Obinutuzumab or Anifrolumab at Inducing Rapid Renal Response in Patients With Lupus Nephritis

The goal of this clinical study is to assess the efficacy and safety of LUPKYNIS® in combination with belimumab, obinutuzumab or anifrolumab at inducing rapid renal response in patients with lupus nephritis (LN).

Patients with LN will be administered LUPKYNIS in combination with belimumab, obinutuzumab or anifrolumab. Additionally, patients will receive treatment with a mycophenolic acid analog (MPAA), specifically mycophenolate mofetil (MMF) or mycophenolic acid (MPA), and oral prednisone (or equivalent).

Key Inclusion Criteria:

• Adults 18-75 years old

• Diagnosed with biopsy-proven lupus nephritis (LN) according to the 2003 International Society of Nephrology (ISN) / Renal Pathology Society (RPS) (class III, class IV, class III/V or class IV/V)

• Urine protein-to-creatine ratio (UPCR) ≥0.5 g/g and <5.0 g/g from a first morning void (FMV) urine sample

• Estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73 m2

• Concomitant biologic:

  • Patients on the belimumab or anifrolumab treatment regimens are receiving belimumab or anifrolumab (as applicable) prior to Screening or will initiate belimumab or anifrolumab (as applicable) on or before Day 1.
  • Patients on the obinutuzumab treatment regimen must have received at least 2 administrations of obinutuzumab prior to Screening.

• Willing to take mycophenolic acid analog (MPAA), either by continuing current MPAA therapy or by initiating it on or before Day 1

• Willing to take corticosteroids, either by continuing current corticosteroids (prednisone [or equivalent]) or by initiating on or before Day 1

Key Exclusion Criteria:

• Any B cell targeted therapy except for the concomitant biologics (belimumab and obinutuzumab) within 1 year prior to Screening unless demonstration of B cell count within the normal range

• Cyclophosphamide or any calcineurin inhibitor other than voclosporin (eg, cyclosporine and tacrolimus) within 3 months prior to Screening

• Any other immunosuppressive therapy except for the concomitant drugs (anifrolumab, MPAAs and oral prednisone [or equivalent]) and immunosuppressive agents used to treat a patient's underlying systemic lupus erythematosus (SLE), including, but not limited to, the examples below, within 30 days or 5 half-lives, whichever is longer, prior to Screening:

  • Anti-tumor necrosis factor (TNF) therapy (eg, adalimumab, etanercept, infliximab)
  • Anti-interleukin therapy (eg, risankizumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tocilizumab, dupilumab)
  • T cell costimulation modulator (eg, abatacept)
  • Intravenous immunoglobulin (IVIg)
  • Janus kinase (JAK) inhibitors (eg, upadacitinib)

• Pregnant, breastfeeding or intending to become pregnant during the Study