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

• ClinicalTrials.gov Identifier: NCT03285711
• Recruitment Status: Completed
• First Posted: September 18, 2017
• Results First Posted: May 18, 2020
• Last Update Posted: May 18, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Lupus Membranous Nephropathy	Drug: Filgotinib; Drug: Lanraplenib; Drug: Filgotinib placebo; Drug: Lanraplenib placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: October 6, 2017
• Actual Primary Completion Date: May 3, 2019
• Actual Study Completion Date: February 3, 2020

Arms and Interventions

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 Name: 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 Name: GS-9876; Drug: Filgotinib placebo; Tablet administered orally once daily

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Change From Baseline (Day 1) in Urine Protein at Week 16 [ Time Frame: Baseline; Week 16 ]
   Urine protein was assessed by urinary protein excretion during a 24-hour urine collection.
2. Change From Baseline (Day 1) in Estimated Glomerular Filtration Rate (eGFR) at Week 16 [ Time Frame: Baseline; Week 16 ]
3. Change From Baseline (Day 1) in Urine Protein Creatinine Ratio (UPCR) at Week 16 [ Time Frame: Baseline; Week 16 ]
   UPCR was assessed by urine protein excretion during a 24-hour urine collection.
4. Percentage of Participants With Partial Remission at Week 16 [ Time Frame: 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]).
5. Percentage of Participants With Complete Remission at Week 16 [ Time Frame: Week 16 ]
   Complete Remission was defined as urine protein excretion below 0.5 g/day, with no hematuria.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham (UAB)

Birmingham, Alabama, United States, 35294

United States, California

Stanford University

Palo Alto, California, United States, 94304

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610-0272

United States, Georgia

Emory University School of Medicine

Atlanta, Georgia, United States, 30303

Georgia Nephrology Research Institute

Lawrenceville, Georgia, United States, 30046

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, North Carolina

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

Chapel Hill, North Carolina, United States, 27599-7155

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Monitor; Gilead Sciences

  Study Documents (Full-Text)

Documents provided by Gilead Sciences:

Study Protocol  [PDF] March 21, 2018

Statistical Analysis Plan  [PDF] January 28, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT03285711
• Other Study ID Numbers: GS-US-437-4093
• First Posted: September 18, 2017
• Results First Posted: May 18, 2020
• Last Update Posted: May 18, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Kidney Diseases; Glomerulonephritis, Membranous; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Nephritis; Autoimmune Diseases; Immune System Diseases