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

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).

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.

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.

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.

https://clinicaltrials.gov: NCT02394106.