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Abstract: TH-PO1220

Phase 2 Open-Label Trial Evaluating the Efficacy and Safety of Obinutuzumab (OBI) in Treatment of Immunosuppression-Resistant Primary FSGS, or Contraindication to High-Dose Steroids: A Two-Year Study

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Zand, Ladan, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Greene, Eddie L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Cheungpasitporn, Wisit, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Vargas-Brochero, Maria J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Sethi, Sanjeev, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Ronco, Pierre M., Hopital Tenon Service d'Urgences nephrologiques et transplantation renale, Paris, Île-de-France, France
  • Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

We investigated the efficacy and safety of OBI, a type II anti-CD20 antibody, in patients with primary FSGS who were resistant/dependent on immunosuppressive therapy.

Methods

Patients received 2 doses of OBI (1g), 2 weeks apart at baseline and 6 m. Primary outcome was proteinuria change from baseline to 6 and 12 months. Secondary endpoints were complete (proteinuria <0.3g/d) or partial (50% reduction with proteinuria < 3.5 g/d) remission, & rates of serious adverse events and sustained proteinuria remission at 24 months.

Results

Twenty patients were enrolled. Average age 45.3±17.5 years, 55% male. Systolic BP: 132±17.5 mmHg, diastolic BP: 77.1±9.5 mmHg. Patients had failed 2-3 prior therapies. Nine patients had received rituximab previously. There was significant reduction in proteinuria from baseline [10.7 (7.5 – 13.7)] g/d to 12 m [3.9 (1.5, 8.6)] and 24 m [1.1 (0.5-5.9)] (p <0.01, p <0.001) (Table 1). At 24 m, 14 patients (70%) reached CR/PR (increased from 45% at 12 m). 3 serious adverse events (SAE): 2 in one patient hospitalized for suicidal ideation and pseudo-seizures, 1 patient development follicular lymphoma. SAEs were considered unrelated to OBI. Most common AE was infusion-related reactions in 7 patients (none discontinued therapy). There were 12 infections (4 COVID19), none required hospitalization.

Conclusion

OBI significantly reduced proteinuria in patients with primary FSGS who had failed 2-3 prior therapies at 12 and 24 months. Reduction in proteinuria was associated with an improvement in serum albumin and lipid panel and acceptable side effect profile.

Patients' laboratory and urine study data
 Baseline (N=20)12 months (N=20)18 months (N=19)24 months (N=19)p-value
Serum creatinine (mg/dL)1.4 (1.0, 2.4)1.3 (1.0, 1.6)1.3 (1.0, 1.5)1.2 (1.0, 1.6)0.34
eGFR (ml/min/BSA)59.6 ± 34.965.9 ± 33.768.5 ± 34.869.1 ± 34.50.23
Serum albumin (g/dL)2.5 ± 0.63.5 ± 0.83.8 ± 0.73.9 ± 0.7<0.001
Total Cholesterol (mg/dL)285 ± 120213 ± 49215 ± 101201 ± 100<0.001
Proteinuria (g/d)10.7 (7.5 , 13.7) 3.8 (1.5 , 8.6) 2.7 (0.8 , 5.6)1.1 (0.6 , 5.5)+<0.001
B-cell counts (cells/μl)160 (75 , 251)0 (0, 0)1 (0, 67)1 (0, 47)<0.001

* p-value is the comparison between baseline and 24 months. + The proteinuria at 24 months was significantly lower compared to 12 months (p<0.01). Results are reported as averages ± standard deviations or median and interquartile.

Funding

  • Commercial Support – Janssen Pharmaceuticals

Digital Object Identifier (DOI)