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

NCT ID: NCT03285711

Last Updated: 2020-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-06
• Study Completion Date: 2020-02-03

Brief Summary

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).

Conditions

Lupus Membranous Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Lanraplenib

Intervention Type: DRUG

30 mg tablet administered orally once daily

Filgotinib placebo

Intervention Type: DRUG

Tablet administered orally once daily

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.

Group Type: EXPERIMENTAL

Filgotinib

Intervention Type: DRUG

200 mg tablet administered orally once daily

Lanraplenib placebo

Intervention Type: DRUG

Tablet administered orally once daily

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.

Group Type: EXPERIMENTAL

Filgotinib

Intervention Type: DRUG

200 mg tablet administered orally once daily

Lanraplenib placebo

Intervention Type: DRUG

Tablet administered orally once daily

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.

Group Type: EXPERIMENTAL

Lanraplenib

Intervention Type: DRUG

30 mg tablet administered orally once daily

Filgotinib placebo

Intervention Type: DRUG

Tablet administered orally once daily

Interventions

Filgotinib

200 mg tablet administered orally once daily

Intervention Type: DRUG

Lanraplenib

30 mg tablet administered orally once daily

Intervention Type: DRUG

Filgotinib placebo

Tablet administered orally once daily

Intervention Type: DRUG

Lanraplenib placebo

Tablet administered orally once daily

Intervention Type: DRUG

Other Intervention Names

GS-6034; GLPG0634; GS-9876

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Monitor

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

University of Alabama at Birmingham (UAB)

Birmingham, Alabama, United States

Stanford University

Palo Alto, California, United States

University of Florida

Gainesville, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Georgia Nephrology Research Institute

Lawrenceville, Georgia, United States

University of Michigan

Ann Arbor, Michigan, United States

University of North Carolina at Chapel Hill / UNC School of Medicine

Chapel Hill, North Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33380521 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GS-US-437-4093

Identifier Type: -

Identifier Source: org_study_id