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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Lupus Membranous Nephropathy

Intervention / Treatment
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* Drug: Filgotinib
* Drug: Lanraplenib
* Drug: Filgotinib placebo
* Drug: Lanraplenib placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lanraplenib 30 mg<br>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<br>* 30 mg tablet administered orally once daily<br>* Other names: GS-9876;Drug: Filgotinib placebo<br>* Tablet administered orally once daily<br>|
| Experimental: Filgotinib 200 mg<br>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<br>* 200 mg tablet administered orally once daily<br>* Other names: GLPG0634;Drug: Lanraplenib placebo<br>* Tablet administered orally once daily<br>|
| Experimental: Lanraplenib 30 mg to Filgotinib 200 mg<br>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<br>* 200 mg tablet administered orally once daily<br>* Other names: GLPG0634;Drug: Lanraplenib placebo<br>* Tablet administered orally once daily<br>|
| Experimental: Filgotinib 200 mg to Lanraplenib 30 mg<br>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<br>* 30 mg tablet administered orally once daily<br>* Other names: GS-9876;Drug: Filgotinib placebo<br>* Tablet administered orally once daily<br>|

What is the study measuring?
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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 |