Study to Evaluate the Safety and Efficacy of Filgotinib and Lanraplenib in Adults With Lupus Membranous Nephropathy (LMN)

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Lupus Membranous Nephropathy

Treatments: Drug: Filgotinib placebo; Drug: Lanraplenib placebo; Drug: Lanraplenib; Drug: Filgotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03285711

GS-US-437-4093

Details and patient eligibility

About

The primary objective of this study is to evaluate the efficacy of filgotinib and lanraplenib (previously GS-9876) in adults with lupus membranous nephropathy (LMN).

Enrollment: 9 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Kidney biopsy within the 36 months prior to screening with a histologic diagnosis of LMN (International Society of Nephrology [ISN] and the Renal Pathology Society [RPS] 2003 classification of lupus nephritis), either Class V alone, or Class V in combination with Class II.
• Urine protein excretion ≥ 1.5 grams per day
• Estimated glomerular filtration rate (eGFR) ≥ 40 mg/min/1.73m^2 based on the modification of diet in renal disease (MDRD) formulation at screening
• No evidence of active or latent tuberculosis (TB) as assessed during screening

Key Exclusion Criteria:

• Prior treatments as follows:

  • Previous treatment with a janus kinase (JAK) inhibitor within 3 months of Day 1
  • Use of rituximab or other selective B lymphocyte depleting agents (including experimental agents) within 6 months of Day 1. Enrollment is permitted if the last dose was given > 6 months and CD19-positive B cells are detectable at Screening.

• Use of any concomitant prohibited medications as described in the protocol

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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9 participants in 4 patient groups

Lanraplenib 30 mg

Experimental group

Description:

Participants receive lanraplenib 30 mg tablet + filgotinib placebo tablet orally once daily for 16 weeks in Blinded Treatment Phase. Participants who achieve ≥ 35% reduction in urinary protein excretion from baseline continue to receive same blinded study treatment for additional 16 weeks. Participants who did not achieve a ≥ 35% reduction in urinary protein excretion will switch treatment. After 32 weeks of blinded treatment, participants who have ≥ 35% reduction in urinary protein excretion from baseline continue their assigned blinded treatment for additional 20 weeks in Extended Blinded Treatment Phase.

Treatment:

Drug: Lanraplenib

Drug: Filgotinib placebo

Filgotinib 200 mg

Experimental group

Description:

Participants receive filgotinib 200 mg tablet + lanraplenib placebo tablet orally once daily for 16 weeks in Blinded Treatment Phase. Participants who achieve ≥ 35% reduction in urinary protein excretion from baseline continue to receive same blinded study treatment for additional 16 weeks. Participants who did not achieve a ≥ 35% reduction in urinary protein excretion will switch treatment. After 32 weeks of blinded treatment, participants who have ≥ 35% reduction in urinary protein excretion from baseline continue their assigned blinded treatment for additional 20 weeks in Extended Blinded Treatment Phase.

Treatment:

Drug: Filgotinib

Drug: Lanraplenib placebo

Lanraplenib 30 mg to Filgotinib 200 mg

Experimental group

Description:

At Week 16, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from baseline to Week 16 switch treatment and receive filgotinib 200 mg + lanraplenib placebo for additional 16 weeks. At Week 32, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from Week 16 to Week 32 can continue whichever treatment that lead to the greatest reduction in urinary protein excretion, or either treatment per investigator's discretion for additional 20 weeks in Extended Blinded Treatment Phase.

Treatment:

Drug: Filgotinib

Drug: Lanraplenib placebo

Filgotinib 200 mg to Lanraplenib 30 mg

Experimental group

Description:

At Week 16, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from baseline to Week 16 switch treatment and receive lanraplenib 30 mg + filgotinib placebo for additional 16 weeks. At Week 32, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from Week 16 to Week 32 can continue whichever treatment that lead to the greatest reduction in urinary protein excretion, or either treatment per investigator's discretion for additional 20 weeks in Extended Blinded Treatment Phase.

Treatment:

Drug: Lanraplenib

Drug: Filgotinib placebo