Low-dose ofatumumab for multidrug-resistant nephrotic syndrome in children: a randomized placebo-controlled trial

Pediatr Nephrol. 2020 Jun;35(6):997-1003. doi: 10.1007/s00467-020-04481-y. Epub 2020 Jan 28.


Background: Children with multidrug-resistant nephrotic syndrome (MRNS) are exposed to drug toxicity (steroids/calcineurin inhibitors (CNI)/mycophenolate mofetil (MMF)) and have an increased risk of kidney disease progression. In small case series, the fully humanized anti-CD20 antibody ofatumumab (OFA) induced remission in children with MRNS when at high dose (10,300 mg/1.73 m2) and partial remission at standard dose (1000 mg/1.73 m2).

Methods: This double-blind randomized placebo-controlled trial tested the efficacy of single infusion OFA in children with proven MRNS and initial chronic renal failure (eGFR [median/range] 119/38-155 ml/min/1.73 m2 in Placebo arm vs. 65/19-103 ml/min/1.73 m2 Intervention). Children who had been resistant to a combination of CNI and steroids, with or without MMF or rituximab, were randomized to receive single infusion OFA (1500 mg/1.73 m2) (Intervention arm) or normal saline (Placebo arm). We assessed complete or partial remission of proteinuria after 3 months (primary outcome), and after 6 and 12 months (secondary outcomes), as well as progression to end-stage kidney disease.

Results: After 13 of the planned 50 children (25%) were randomized, the data safety and monitoring board recommended study termination for futility. All 13 children remained nephrotic. Renal function worsened in 5 children (2 in Intervention arm, 3 in Placebo arm) who required renal replacement therapy during the study period. Circulating CD20 was reduced following OFA infusion and remained low for > 3 months.

Conclusions: OFA given in one single infusion of 1500 mg/1.73 m2 doses does not induce remission in MRNS. Regimens based on higher OFA doses should be tested in clinical trials.

Trial registration: https://clinicaltrials.gov: NCT02394106.

Keywords: Children; Multidrug-resistant nephrotic syndrome; Ofatumumab; Remission.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Drug Resistance, Multiple / drug effects
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Nephrotic Syndrome / drug therapy*
  • Remission Induction / methods
  • Treatment Failure


  • Antibodies, Monoclonal, Humanized
  • ofatumumab

Associated data

  • ClinicalTrials.gov/NCT02394106