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

A Phase 2, Randomized, Double-Blind, Multicenter Study Evaluating the Safety and Efficacy of Filgotinib and GS-9876 in Subjects With Lupus Membranous Nephropathy (LMN)

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).

Study Overview

• Status: Completed
• Conditions: Lupus Membranous Nephropathy
• Intervention / Treatment: Drug: Filgotinib; Drug: Lanraplenib; Drug: Filgotinib placebo; Drug: Lanraplenib placebo

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham (UAB)
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Florida
    • Gainesville, Florida, United States, 32610-0272
      • University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University School Of Medicine
    • Lawrenceville, Georgia, United States, 30046
      • Georgia Nephrology Research Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7155
      • University of North Carolina at Chapel Hill / UNC School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lanraplenib 30 mg; 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.	Drug: Lanraplenib; 30 mg tablet administered orally once daily; Other Names: GS-9876; Drug: Filgotinib placebo; Tablet administered orally once daily
Experimental: Filgotinib 200 mg; 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.	Drug: Filgotinib; 200 mg tablet administered orally once daily; Other Names: GS-6034; GLPG0634; Drug: Lanraplenib placebo; Tablet administered orally once daily
Experimental: Lanraplenib 30 mg to Filgotinib 200 mg; 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.	Drug: Filgotinib; 200 mg tablet administered orally once daily; Other Names: GS-6034; GLPG0634; Drug: Lanraplenib placebo; Tablet administered orally once daily
Experimental: Filgotinib 200 mg to Lanraplenib 30 mg; 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.	Drug: Lanraplenib; 30 mg tablet administered orally once daily; Other Names: GS-9876; Drug: Filgotinib placebo; Tablet administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Urine Protein From Baseline (Day 1) to Week 16	Urine protein was assessed by urinary protein excretion during a 24-hour urine collection.	Baseline; Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline (Day 1) in Urine Protein at Week 16	Urine protein was assessed by urinary protein excretion during a 24-hour urine collection.	Baseline; Week 16
Change From Baseline (Day 1) in Estimated Glomerular Filtration Rate (eGFR) at Week 16		Baseline; Week 16
Change From Baseline (Day 1) in Urine Protein Creatinine Ratio (UPCR) at Week 16	UPCR was assessed by urine protein excretion during a 24-hour urine collection.	Baseline; Week 16
Percentage of Participants With Partial Remission at Week 16	Partial Remission was defined as urine protein excretion below < 3 g/day and urine protein excretion decrease by ≥ 50% among participants with baseline (Day 1) nephrotic range proteinuria [urine protein excretion ≥ 3 g/day]; or urine protein excretion decrease by ≥ 50% among participants with subnephrotic range proteinuria [urine protein excretion < 3 g/day]).	Week 16
Percentage of Participants With Complete Remission at Week 16	Complete Remission was defined as urine protein excretion below 0.5 g/day, with no hematuria.	Week 16

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Monitor, Gilead Sciences

Publications and helpful links

General Publications

• Baker M, Chaichian Y, Genovese M, Derebail V, Rao P, Chatham W, Bubb M, Lim S, Hajian H, Gurtovaya O, Patel U, Tumlin J. Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy. RMD Open. 2020 Dec;6(3):e001490. doi: 10.1136/rmdopen-2020-001490.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2017
• Primary Completion (Actual): May 3, 2019
• Study Completion (Actual): February 3, 2020

Study Registration Dates

• First Submitted: September 14, 2017
• First Submitted That Met QC Criteria: September 14, 2017
• First Posted (Actual): September 18, 2017

Study Record Updates

• Last Update Posted (Actual): May 18, 2020
• Last Update Submitted That Met QC Criteria: May 1, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, Membranous
• Other Study ID Numbers: GS-US-437-4093

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No