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

NCT03285711 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: GS-US-437-4093
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 7

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change From Baseline (Day 1) in Urine Protein at Week 16

  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

  Baseline; Week 16

• Percentage of Participants With Partial Remission at Week 16

  Week 16

• Percentage of Participants With Complete Remission at Week 16

  Week 16

Study Arms (4)

Lanraplenib 30 mg

EXPERIMENTAL

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; Drug: Filgotinib placebo

Filgotinib 200 mg

EXPERIMENTAL

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; Drug: Lanraplenib placebo

Lanraplenib 30 mg to Filgotinib 200 mg

EXPERIMENTAL

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; Drug: Lanraplenib placebo

Filgotinib 200 mg to Lanraplenib 30 mg

EXPERIMENTAL

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; Drug: Filgotinib placebo

Interventions

Filgotinib DRUG

200 mg tablet administered orally once daily

Also known as: GS-6034, GLPG0634

Filgotinib 200 mg; Lanraplenib 30 mg to Filgotinib 200 mg

Lanraplenib DRUG

30 mg tablet administered orally once daily

Also known as: GS-9876

Filgotinib 200 mg to Lanraplenib 30 mg; Lanraplenib 30 mg

Filgotinib placebo DRUG

Tablet administered orally once daily

Filgotinib 200 mg to Lanraplenib 30 mg; Lanraplenib 30 mg

Lanraplenib placebo DRUG

Tablet administered orally once daily

Filgotinib 200 mg; Lanraplenib 30 mg to Filgotinib 200 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (7)

University of Alabama at Birmingham (UAB)

Birmingham, Alabama, 35294, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of Florida

Gainesville, Florida, 32610-0272, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30303, United States

Location

Georgia Nephrology Research Institute

Lawrenceville, Georgia, 30046, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

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

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

Location

Related Publications (1)

• 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.

  PMID: 33380521 DERIVED

MeSH Terms

Interventions

GLPG0634

Limitations and Caveats

Gilead made a decision to discontinue enrollment after very low enrollment over 16 months. This decision was not due to any safety concerns. Only 9 participants were enrolled and 3 participants completed study, no inferential analyses were performed.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Monitor

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2017
• First Posted: September 18, 2017
• Study Start: October 6, 2017
• Primary Completion: May 3, 2019
• Study Completion: February 3, 2020
• Last Updated: May 18, 2020
• Results First Posted: May 18, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)