Belimumab With Rituximab for Primary Membranous Nephropathy

Summary

Participation Requirements

Description

This trial is a two-part study (Part A and Part B) of adults with primary membranous nephropathy (MN), ages 18-75 inclusive. The study will be conducted at multiple sites in the United States and Canada. Part A: Open-label Phase Part A is an open-label, pharmacokinetics (PK) phase to compare belimum...

This trial is a two-part study (Part A and Part B) of adults with primary membranous nephropathy (MN), ages 18-75 inclusive. The study will be conducted at multiple sites in the United States and Canada. Part A: Open-label Phase Part A is an open-label, pharmacokinetics (PK) phase to compare belimumab exposure between participants who have "low" proteinuria (? 4 to < 8 g/day) and "high" proteinuria (? 8 g/day) at the Screening Visit, Visit-1. Part A will enroll 20 individuals with primary MN: 10 individuals with low proteinuria and 10 individuals with high proteinuria. All Part A participants will receive 200 mg subcutaneous belimumab weekly for 52 doses (weeks 0-51), unless a dose increase is warranted by the PK analysis. Trough serum belimumab levels will be obtained weekly following the first 4 doses of belimumab. Participants will receive rituximab 1000 mg intravenously (IV) at weeks 4 and 6. All participants will be followed after the 52 week treatment period on no study medication until week 156. Belimumab serum trough levels will be analyzed after all participants receive the first 4 belimumab doses to compare belimumab exposure between the low and high proteinuria groups. Belimumab serum trough levels will also be analyzed to determine if a different proteinuria level (instead of 8 g/day) warrants increased belimumab dosing and should be used to define "high" proteinuria. Dose determinations for participants with high proteinuria in Parts A and B will be made by an adjudication committee. The study participation phase is 156 weeks (3 years), which includes a treatment phase of 52 weeks and a post-treatment observation phase of 104 weeks. Part B: Randomized Phase Part B is a prospective, randomized, phase II, double-blind, placebo-controlled, multicenter clinical trial in adults with primary MN. Part B will commence after the analysis of the PK data in Part A. A total of 104 participants will be randomized in a 1:1 fashion into two treatment arms. Randomization will be stratified by low and high proteinuria as determined by the identified threshold in Part A. Participants in both arms will receive rituximab 1000 mg IV at weeks 4 and 6. Participants randomized to the experimental arm will receive subcutaneous belimumab 200 mg weekly for 52 doses (weeks 0-51), unless the results from Part A indicate that participants with high proteinuria should receive belimumab 400 mg weekly. If the participant's proteinuria subsequently decreases to below the high proteinuria threshold, the belimumab dose will be decreased to 200 mg weekly for the remainder of the treatment phase. Participants randomized to the comparator arm will receive subcutaneous belimumab placebo according to the same dose and schedule. The study participation phase is 156 weeks (3 years), which includes a treatment phase of 52 weeks and a post-treatment observation phase of 104 weeks.

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