Lupus Membranous Nephropathy
Conditions
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).
Interventions
DRUGFilgotinib
200 mg tablet administered orally once daily
DRUGLanraplenib
30 mg tablet administered orally once daily
Tablet administered orally once daily
Tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Urine Protein From Baseline (Day 1) to Week 16 | Baseline; Week 16 | Urine protein was assessed by urinary protein excretion during a 24-hour urine collection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Day 1) in Urine Protein at Week 16 | Baseline; 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 | Baseline; Week 16 | — |
| Change From Baseline (Day 1) in Urine Protein Creatinine Ratio (UPCR) at Week 16 | Baseline; Week 16 | UPCR was assessed by urine protein excretion during a 24-hour urine collection. |
| Percentage of Participants With Partial Remission at Week 16 | 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 | Week 16 | Complete Remission was defined as urine protein excretion below 0.5 g/day, with no hematuria. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in United States. The first participant was screened on 06 October 2017. The last study visit occurred on 03 February 2020.
Pre-assignment details
22 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Lanraplenib 30 mg Participants were randomized to receive lanraplenib 30 mg tablet + filgotinib placebo tablet orally once daily for 16 weeks in Blinded Treatment Phase. | 4 |
| Filgotinib 200 mg Participants were randomized to receive filgotinib 200 mg tablet + lanraplenib placebo tablet orally once daily for 16 weeks in Blinded Treatment Phase. | 5 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Blinded Phase (Up to Week 16) | Adverse Event | 2 | 1 | 0 | 0 |
| Blinded Phase (Up to Week 16) | Protocol Violation | 1 | 0 | 0 | 0 |
| Blinded Phase (Week 16 to 32) | Lack of Efficacy | 0 | 0 | 1 | 0 |
| Extended Blinded Phase (Week 32 to 52) | Lack of Efficacy | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Lanraplenib 30 mg | Filgotinib 200 mg | Total |
|---|---|---|---|
| 24-Hour Urine Protein | 6.0 g/day STANDARD_DEVIATION 4.65 | 3.3 g/day STANDARD_DEVIATION 2.47 | 4.5 g/day STANDARD_DEVIATION 3.62 |
| Age, Continuous | 36 years STANDARD_DEVIATION 15.8 | 35 years STANDARD_DEVIATION 16.9 | 35 years STANDARD_DEVIATION 15.4 |
| Estimated Glomerular Filtration Rate (eGFR) | 116.1 mL/min/1.73m^2 STANDARD_DEVIATION 55.41 | 102.6 mL/min/1.73m^2 STANDARD_DEVIATION 30.61 | 108.6 mL/min/1.73m^2 STANDARD_DEVIATION 40.87 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
| Urine Protein Creatinine Ratio (UPCR) | 5.1 mg/mg STANDARD_DEVIATION 4.38 | 1.9 mg/mg STANDARD_DEVIATION 1.04 | 3.3 mg/mg STANDARD_DEVIATION 3.23 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 5 | 0 / 0 | 0 / 3 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 4 / 4 | 3 / 5 | 0 / 0 | 1 / 3 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 1 / 4 | 0 / 5 | 0 / 0 | 0 / 3 | 0 / 1 | 0 / 1 |
Outcome results
Primary
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.
Time frame: Baseline; Week 16
Population: Participants in the Full Analysis Set (included all randomized participants who took at least 1 dose of study drug) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanraplenib 30 mg | Percent Change in Urine Protein From Baseline (Day 1) to Week 16 | -2.8 percent change | — |
| Filgotinib 200 mg | Percent Change in Urine Protein From Baseline (Day 1) to Week 16 | -51.2 percent change | Standard Deviation 25.67 |
Secondary
Change From Baseline (Day 1) in Estimated Glomerular Filtration Rate (eGFR) at Week 16
Time frame: Baseline; Week 16
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanraplenib 30 mg | Change From Baseline (Day 1) in Estimated Glomerular Filtration Rate (eGFR) at Week 16 | -59.4 mL/min/1.73 m^2 | — |
| Filgotinib 200 mg | Change From Baseline (Day 1) in Estimated Glomerular Filtration Rate (eGFR) at Week 16 | -2.0 mL/min/1.73 m^2 | Standard Deviation 11.35 |
Secondary
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.
Time frame: Baseline; Week 16
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanraplenib 30 mg | Change From Baseline (Day 1) in Urine Protein at Week 16 | -0.177 g/day | — |
| Filgotinib 200 mg | Change From Baseline (Day 1) in Urine Protein at Week 16 | -2.151 g/day | Standard Deviation 2.2591 |
Secondary
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.
Time frame: Baseline; Week 16
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanraplenib 30 mg | Change From Baseline (Day 1) in Urine Protein Creatinine Ratio (UPCR) at Week 16 | -4.407 mg/mg | — |
| Filgotinib 200 mg | Change From Baseline (Day 1) in Urine Protein Creatinine Ratio (UPCR) at Week 16 | -0.808 mg/mg | Standard Deviation 0.7539 |
Secondary
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.
Time frame: Week 16
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanraplenib 30 mg | Percentage of Participants With Complete Remission at Week 16 | 0 percentage of participants |
| Filgotinib 200 mg | Percentage of Participants With Complete Remission at Week 16 | 0 percentage of participants |
Secondary
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 \[urine protein excretion \< 3 g/day\]).
Time frame: Week 16
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanraplenib 30 mg | Percentage of Participants With Partial Remission at Week 16 | 0 percentage of participants |
| Filgotinib 200 mg | Percentage of Participants With Partial Remission at Week 16 | 50.0 percentage of participants |