Study to Evaluate Safety and Efficacy of Filgotinib and Lanraplenib in Females With Moderately-to-Severely Active Cutaneous Lupus Erythematosus (CLE)

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 (formerly GS-9876) in females with moderately-to-severely active cutaneous lupus erythematosus (CLE).

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Filgotinib and GS-9876 in Female Subjects With Moderately-to-Severely Active Cutaneous Lupus Erythematosus (CLE)

Conditions
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Cutaneous Lupus Erythematosus

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


Participation Criteria
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Eligibility Criteria
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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 and Day 1 Prior intolerance or inadequate response to at least one of the listed medications for the treatment of CLE Stable dose (defined as no change in prescription for at least 28 days prior to Day 1) of antimalarials and/or topical or oral corticosteroids is permitted during the study. Individuals who are not planning to continue these medications during the study must have discontinued them at least 28 days prior to Day 1 Key Exclusion Criteria: Use of prohibited concomitant medications per study 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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Female

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lanraplenib 30 mg<br>Lanraplenib + filgotinib placebo for 48 weeks | Drug: Lanraplenib<br>* 30 mg tablets administered orally once daily with or without food<br>* Other names: GS-9876;Drug: Filgotinib placebo<br>* Tablets administered orally once daily with or without food<br>|
| Experimental: Filgotinib 200 mg<br>Filgotinib + lanraplenib placebo for 48 weeks | Drug: Filgotinib<br>* 200 mg tablets administered orally once daily with or without food<br>* Other names: GS-6034;Drug: Lanraplenib placebo<br>* Tablets administered orally once daily with or without food<br>|
| Placebo Comparator: Placebo<br>Filgotinib placebo + lanraplenib placebo for 12 weeks | Drug: Lanraplenib placebo<br>* Tablets administered orally once daily with or without food<br>Drug: Filgotinib placebo<br>* Tablets administered orally once daily with or without food<br>|
| Experimental: Placebo to Lanraplenib 30 mg<br>After Week 12 Visit, participants on placebo will be rerandomized 1:1 and receive lanraplenib + filgotinib placebo in a blinded fashion through Week 48. | Drug: Lanraplenib<br>* 30 mg tablets administered orally once daily with or without food<br>* Other names: GS-9876;Drug: Filgotinib placebo<br>* Tablets administered orally once daily with or without food<br>|
| Experimental: Placebo to Filgotinib 200 mg<br>After Week 12 Visit, participants on placebo will be rerandomized 1:1 and receive filgotinib + lanraplenib placebo in a blinded fashion through Week 48. | Drug: Filgotinib<br>* 200 mg tablets administered orally once daily with or without food<br>* Other names: GS-6034;Drug: Lanraplenib placebo<br>* Tablets administered orally once daily with or without food<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score From Baseline to Week 12 | 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. | Baseline; Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants at Week 12 With Decrease of ≥ 5 Points in CLASI Activity Score From Baseline | 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. | Baseline; Week 12 | 
| Percentage of Participants at Week 12 With No Worsening in CLASI Activity Score From Baseline | 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. Worsening was defined as ≥ 3 point increase in CLASI activity score. | Baseline; Week 12 | 
| Percentage of Participants at Week 24 With Decrease of ≥ 5 Points in CLASI Activity Score From Baseline | 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. | Baseline; Week 24 | 
| Percentage of Participants at Week 24 With No Worsening in CLASI Activity Score From Baseline | 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. Worsening was defined as ≥ 3 point increase in CLASI activity score. | Baseline; Week 24 |