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Abstract: PO1623

Itolizumab, a Novel Anti-CD6 Therapy, in Systemic Lupus Erythematosus Patients: Interim Safety Results from the Phase 1b EQUALISE Dose-Escalation Study

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Putterman, Chaim, Yeshiva University Department of Medicine, Bronx, New York, United States
  • Furie, Richard, Northwell Health, New Hyde Park, New York, United States
  • Radhakrishnan, Jai, Columbia University, New York, New York, United States
  • Mathur, Vandana S., Equillium, Inc, La Jolla, California, United States
  • Polu, Krishna Reddy, Equillium, Inc, La Jolla, California, United States
  • Connelly, Stephen, Equillium, Inc, La Jolla, California, United States
  • Rothman, Joel M., Equillium, Inc, La Jolla, California, United States
  • Ng, Cherie T., Equillium, Inc, La Jolla, California, United States
  • Chinn, Leslie, Equillium, Inc, La Jolla, California, United States
  • Fung, Maple M., Equillium, Inc, La Jolla, California, United States
  • Thomas, Dolca, Equillium, Inc, La Jolla, California, United States
  • Kalunian, Kenneth, University of California San Diego, La Jolla, California, United States
Background

CD6 is a co-stimulatory receptor predominantly expressed on T cells. The CD6 ligand, ALCAM, is expressed on antigen presenting cells, epithelial and endothelial cells. Itolizumab (ITO) is a humanized IgG1 monoclonal antibody that binds CD6 and blocks ALCAM interaction to inhibit T cell activation and trafficking.

Methods

EQUALISE is an open-label Phase 1b 2-part study evaluating the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of subcutaneous doses (SC) of ITO (0.4 to 3.2 mg/kg). Part A enrolled adults with active or inactive SLE who received ≥1 SLE treatment. Treated subjects received ITO SC Q2 weeks x 2. Part B, which evaluates ITO in subjects with active proliferative Class III/IV LN for 24 weeks, is currently enrolling (NCT04128579).

Results

Part A enrolled 34 subjects: 0.4 mg/kg (n=6), 0.8 mg/kg (n=7), 1.6 mg/kg (n=7), 2.4 mg/kg (n=6), and 3.2 mg/kg (n=8). Similar baseline characteristics were noted across cohorts. The mean age was 51, with 94% female, 74% white and ~11 years since SLE diagnosis. C3 and C4 were within normal ranges. Mean eGFR was 98 ml/min/1.73m2 and the median UPCR was 91 mg/g (range 48-1505).
SC dosing of 0.4 mg/kg to 2.4 mg/kg (n=26) was well tolerated, with 38% reporting an AE, predominantly mild injection site reactions, with no SAEs reported. >85% of 3.2 mg/kg subjects reported an AE, the most common was injection site reactions, with 2 non-treatment related SAEs reported in 1 subject (hypotension, syncope). 4 3.2 mg/kg subjects (50%) discontinued treatment after 1 dose voluntarily. In all cohorts, there were no notable changes in vital signs or labs, except for transient declines in lymphocyte counts without clinical sequelae.
PK and PD results show dose-proportional increases in ITO exposure and rapid and dose-dependent decreases in CD4 cell surface expression of CD6.

Conclusion

2 SC doses of ITO up to 2.4 mg/kg SC in SLE subjects were well tolerated; with less tolerability to the 3.2 mg/kg dose, as 50% discontinued after 1 dose. The data support continued evaluation of ITO in SLE/LN. The ongoing EQUALISE Part B assesses ITO safety and efficacy in Class III/IV LN patients.

Funding

  • Commercial Support