Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GS-9876
Lanraplenib · 4 trials · 4 indications
CLASI Activity is scored based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and nonscarring alopecia. Evaluation of erythema and scale/hyperkeratosis is based on a table: rows represent anatomical areas and columns represent major clinical symptoms. The extent of involvement for each of the skin symptoms is documented for each anatomic area. The total score ranges from 0-70, with higher scores indicating more severe skin disease.
Response was defined as: Improvement ≥ 20% in ≥ 3 of 5 participant-reported Sjogren's syndrome (SjS) related visual analogue score (VAS) measures (participant's assessment of global disease, pain, oral dryness, ocular dryness and fatigue), with no increase defined as \> 30 mm from baseline (Day 1) in any of the above 5 VAS measures, AND either ≥ 20% improvement in high sensitivity C-reactive protein (hsCRP) (if hsCRP ≥ 1.5 x upper limit of normal \[ULN\] on Day 1) or no increase in hsCRP to ≥ 1.5 x ULN (if hsCRP \< 1.5 x ULN on Day 1).
Disease Activity Score 28 C-Reactive Protein (DAS28 (CRP)) is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), participant's global assessment of disease activity (visual analog scale: 0 = no disease activity to 100 = maximum disease activity) and C-Reactive Protein (CRP) for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.
AUClast is defined as the concentration of drug from time zero to the last observable concentration. CLcr was estimated using the CG equation for renal function as recommended by the FDA and international guidance documents. CG equation: For men: CLcr (mL/min) = (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) For women: CLcr (mL/min) = 0.85 × (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) Participants were classified based on estimated CLcr as: Moderate renal impairment: CLcr 30-59 mL/min Severe renal impairment: CLcr 15-29 mL/min Healthy control: CLcr ≥ 90 mL/min
AUCinf is defined as the concentration of drug extrapolated to infinite time. CLcr was estimated using the CG equation for renal function as recommended by the FDA and international guidance documents. CG equation: For men: CLcr (mL/min) = (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) For women: CLcr (mL/min) = 0.85 × (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) Participants were classified based on estimated CLcr as: Moderate renal impairment: CLcr 30-59 mL/min Severe renal impairment: CLcr 15-29 mL/min Healthy control: CLcr ≥ 90 mL/min
Cmax is defined as the maximum concentration of drug. CLcr was estimated using the CG equation for renal function as recommended by the FDA and international guidance documents. CG equation: For men: CLcr (mL/min) = (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) For women: CLcr (mL/min) = 0.85 × (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) Participants were classified based on estimated CLcr as: Moderate renal impairment: CLcr 30-59 mL/min Severe renal impairment: CLcr 15-29 mL/min Healthy control: CLcr ≥ 90 mL/min
| Arm | Type | Description |
|---|---|---|
| Lanraplenib 30 mg | EXPERIMENTAL | Lanraplenib + filgotinib placebo for 48 weeks |
| Filgotinib 200 mg | EXPERIMENTAL | Filgotinib + lanraplenib placebo for 48 weeks |
| Placebo | PLACEBO_COMPARATOR | Filgotinib placebo + lanraplenib placebo for 12 weeks |
| Placebo to Lanraplenib 30 mg | EXPERIMENTAL | After Week 12 Visit, participants on placebo will be rerandomized 1:1 and receive lanraplenib + filgotinib placebo in a blinded fashion through Week 48. |
| Placebo to Filgotinib 200 mg | EXPERIMENTAL | After Week 12 Visit, participants on placebo will be rerandomized 1:1 and receive filgotinib + lanraplenib placebo in a blinded fashion through Week 48. |
| Lanraplenib | EXPERIMENTAL | Lanraplenib + filgotinib placebo + tirabrutinib placebo for up to 49.4 weeks. |
| Filgotinib | EXPERIMENTAL | Filgotinib + lanraplenib placebo + tirabrutinib placebo for up to 50.4 weeks. |
| Tirabrutinib | EXPERIMENTAL | Tirabrutinib + filgotinib placebo + lanraplenib placebo for up to 50.3 weeks. |
| Placebo, then active treatment | PLACEBO_COMPARATOR | Filgotinib placebo + lanraplenib placebo + tirabrutinib placebo for 24 weeks. Following completion of the Week 24 assessments and procedures, participants will be rerandomized 1:1:1, in a blinded fashion and receive either of the following study drugs through Week 48: * filgotinib + lanraplenib placebo + tirabrutinib placebo * lanraplenib + filgotinib placebo + tirabrutinib placebo * tirabrutinib + filgotinib placebo + lanraplenib placebo |
| GS-9876 - 30 mg | EXPERIMENTAL | GS-9876 30 mg + filgotinib placebo for 12 weeks |
| GS-9876 - 10 mg | EXPERIMENTAL | GS-9876 10 mg + filgotinib placebo for 12 weeks |
| Moderate Renal Impairment (Cohort 1) | EXPERIMENTAL | Participants with moderate renal impairment and matched healthy controls will receive a single dose of lanraplenib |
| Severe Renal Impairment (Adaptive Cohort 2) | EXPERIMENTAL | Participants with severe renal impairment and matched healthy controls will receive a single dose of lanraplenib |
| Mild Renal Impairment (Adaptive Cohort 3) | EXPERIMENTAL | Participants with mild renal impairment and matched healthy controls will receive a single dose of lanraplenib |
| Name | Type | Description |
|---|---|---|
| Lanraplenib | DRUG | 30 mg tablets administered orally once daily with or without food |
| Filgotinib | DRUG | 200 mg tablets administered orally once daily with or without food |
| Lanraplenib placebo | DRUG | Tablets administered orally once daily with or without food |
| Filgotinib placebo | DRUG | Tablets administered orally once daily with or without food |
| Tirabrutinib | DRUG | 1 x 40 mg tablet administered orally once daily |
| Tirabrutinib placebo | DRUG | 1 x tablet administered orally once daily |
| GS-9876 | DRUG | One tablet administered orally once daily |
| GS-9876 placebo | DRUG | One tablet administered orally once daily |
| Methotrexate | DRUG | Background therapy with methotrexate administered orally or parenterally once weekly |
| Lanraplenib. | DRUG | 20 mg (2 X 10 mg) tablets administered orally in a fasted state on Day 1 |
Key Inclusion Criteria: * Must have a diagnosis of CLE, either chronic (e.g., discoid) or subacute CLE per investigator evaluation, with the following: * Moderately-to-severely active CLE (Cutaneous lupus erythematosus disease area and severity index \[CLASI\] activity score ≥ 10) at screening a...
Lanraplenib is an investigational small molecule developed by Gilead Sciences, Inc. (ticker GILD) for immunology indications. It has been studied in cutaneous lupus erythematosus, Sjogren's syndrome, and inflammatory disease. It is a SYK inhibitor and remains in clinical development rather than being an approved medicine.
Lanraplenib has been studied in cutaneous lupus erythematosus, Sjogren's syndrome, and inflammatory disease. Its clinical program includes a Phase 2 trial in moderately-to-severely active cutaneous lupus erythematosus in females and a Phase 2 trial in adults with active Sjogren's syndrome. It is investigational and not an approved treatment.
Lanraplenib targets SYK, also called spleen tyrosine kinase. It acts as a SYK inhibitor, a small molecule designed to block signaling through this kinase. SYK is a target of interest in immunology research, and lanraplenib's development has focused on immune-mediated conditions such as cutaneous lupus erythematosus and Sjogren's syndrome.
Gilead Sciences, Inc., which trades under the ticker GILD, is the developer of lanraplenib. The company has sponsored the clinical studies of the compound in immunology indications, including cutaneous lupus erythematosus and Sjogren's syndrome.
Lanraplenib is in Phase 2 development. Its Phase 2 studies include NCT03134222 in cutaneous lupus erythematosus and NCT03100942 in Sjogren's syndrome, both completed. A Phase 1 pharmacokinetic study, NCT02959138, evaluated the drug in adults with impaired renal function. Lanraplenib is investigational and has not been approved by the FDA.
Lanraplenib has been evaluated in completed trials including NCT03134222, a Phase 2 study in females with moderately-to-severely active cutaneous lupus erythematosus, and NCT03100942, a Phase 2 study in adults with active Sjogren's syndrome. NCT02959138 was a Phase 1 pharmacokinetic study in adults with impaired renal function.