Back to resultsStudy to Evaluate the Safety and Efficacy of Filgotinib and Lanraplenib in Adults With Lupus Membranous Nephropathy (LMN)
Primary Purpose
Lupus Membranous Nephropathy
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Filgotinib
Lanraplenib
Filgotinib placebo
Lanraplenib placebo
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Membranous Nephropathy
Eligibility 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.
Sites / Locations
- University of Alabama at Birmingham (UAB)
- Stanford University
- University of Florida
- Emory University School of Medicine
- Georgia Nephrology Research Institute
- University of Michigan
- University of North Carolina at Chapel Hill / UNC School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Lanraplenib 30 mg
Filgotinib 200 mg
Lanraplenib 30 mg to Filgotinib 200 mg
Filgotinib 200 mg to Lanraplenib 30 mg
Arm 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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Change From Baseline (Day 1) in Estimated Glomerular Filtration Rate (eGFR) at 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.
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]).
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03285711
Brief Title
Study to Evaluate the Safety and Efficacy of Filgotinib and Lanraplenib in Adults With Lupus Membranous Nephropathy (LMN)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
October 6, 2017 (Actual)
Primary Completion Date
May 3, 2019 (Actual)
Study Completion Date
February 3, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Membranous Nephropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lanraplenib 30 mg
Arm Type
Experimental
Arm 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.
Arm Title
Filgotinib 200 mg
Arm Type
Experimental
Arm 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.
Arm Title
Lanraplenib 30 mg to Filgotinib 200 mg
Arm Type
Experimental
Arm 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.
Arm Title
Filgotinib 200 mg to Lanraplenib 30 mg
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Filgotinib
Other Intervention Name(s)
GS-6034, GLPG0634
Intervention Description
200 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Lanraplenib
Other Intervention Name(s)
GS-9876
Intervention Description
30 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Filgotinib placebo
Intervention Description
Tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Lanraplenib placebo
Intervention Description
Tablet administered orally once daily
Primary Outcome Measure Information:
Title
Percent Change in Urine Protein From Baseline (Day 1) to Week 16
Description
Urine protein was assessed by urinary protein excretion during a 24-hour urine collection.
Time Frame
Baseline; Week 16
Secondary Outcome Measure Information:
Title
Change From Baseline (Day 1) in Urine Protein at Week 16
Description
Urine protein was assessed by urinary protein excretion during a 24-hour urine collection.
Time Frame
Baseline; Week 16
Title
Change From Baseline (Day 1) in Estimated Glomerular Filtration Rate (eGFR) at Week 16
Time Frame
Baseline; Week 16
Title
Change From Baseline (Day 1) in Urine Protein Creatinine Ratio (UPCR) at Week 16
Description
UPCR was assessed by urine protein excretion during a 24-hour urine collection.
Time Frame
Baseline; Week 16
Title
Percentage of Participants With Partial Remission at Week 16
Description
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]).
Time Frame
Week 16
Title
Percentage of Participants With Complete Remission at Week 16
Description
Complete Remission was defined as urine protein excretion below 0.5 g/day, with no hematuria.
Time Frame
Week 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Monitor
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham (UAB)
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0272
Country
United States
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Georgia Nephrology Research Institute
City
Lawrenceville
State/Province
Georgia
ZIP/Postal Code
30046
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of North Carolina at Chapel Hill / UNC School of Medicine
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7155
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33380521
Citation
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.
Results Reference
derived
Learn more about this trial
Study to Evaluate the Safety and Efficacy of Filgotinib and Lanraplenib in Adults With Lupus Membranous Nephropathy (LMN)
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