Cutaneous Lupus Erythematosus
Conditions
Brief summary
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).
Interventions
DRUGLanraplenib
30 mg tablets administered orally once daily with or without food
DRUGFilgotinib
200 mg tablets administered orally once daily with or without food
Tablets administered orally once daily with or without food
Tablets administered orally once daily with or without food
Sponsors
Galapagos NV
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score From Baseline to Week 12 | Baseline; 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants at Week 12 With Decrease of ≥ 5 Points in CLASI Activity Score From Baseline | Baseline; 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. |
| Percentage of Participants at Week 12 With No Worsening in CLASI Activity Score From Baseline | Baseline; 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. Worsening was defined as ≥ 3 point increase in CLASI activity score. |
| Percentage of Participants at Week 24 With Decrease of ≥ 5 Points in CLASI Activity Score From Baseline | Baseline; Week 24 | 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. |
| Percentage of Participants at Week 24 With No Worsening in CLASI Activity Score From Baseline | Baseline; Week 24 | 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. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States and Canada. The first participant was screened on 24 May 2017. The last study visit occurred on 18 December 2019.
Pre-assignment details
72 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Lanraplenib 30 mg Lanraplenib 30 mg + filgotinib placebo tablets orally once daily for 48 weeks | 19 |
| Filgotinib 200 mg Filgotinib 200 mg + lanraplenib placebo tablets orally once daily for 48 weeks | 17 |
| Placebo Participants received filgotinib placebo + lanraplenib placebo tablets orally once daily for 12 weeks. After Week 12 Visit, participants were rerandomized 1:1 and received filgotinib 200 mg + lanraplenib placebo or lanraplenib 30 mg + filgotinib placebo once daily in a blinded fashion through Week 48. | 9 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Treatment Period (Up to Week 12) | Adverse Event | 4 | 1 | 0 | 0 | 0 |
| Treatment Period (Up to Week 12) | Lost to Follow-up | 1 | 1 | 1 | 0 | 0 |
| Treatment Period (Up to Week 12) | Randomized but not treated | 0 | 1 | 1 | 0 | 0 |
| Treatment Period (Up to Week 12) | Withdrew Consent | 0 | 1 | 0 | 0 | 0 |
| Treatment Period (Week 12 to 48) | Investigator's Discretion | 0 | 0 | 0 | 1 | 0 |
| Treatment Period (Week 12 to 48) | Lack of Efficacy | 2 | 0 | 0 | 0 | 0 |
| Treatment Period (Week 12 to 48) | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Treatment Period (Week 12 to 48) | Withdrew Consent | 0 | 2 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Lanraplenib 30 mg | Filgotinib 200 mg |
|---|---|---|---|---|
| Age, Continuous | 47 years STANDARD_DEVIATION 10.1 | 46 years STANDARD_DEVIATION 7.3 | 51 years STANDARD_DEVIATION 9 | 43 years STANDARD_DEVIATION 11.5 |
| Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score | 17.6 score on a scale STANDARD_DEVIATION 9.89 | 14.8 score on a scale STANDARD_DEVIATION 4.79 | 17.1 score on a scale STANDARD_DEVIATION 6.11 | 19.7 score on a scale STANDARD_DEVIATION 14.35 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 15 Participants | 1 Participants | 6 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 9 Participants | 2 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 36 Participants | 7 Participants | 16 Participants | 13 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 25 Participants | 6 Participants | 12 Participants | 7 Participants |
| Region of Enrollment Canada | 8 participants | 3 participants | 4 participants | 1 participants |
| Region of Enrollment United States | 37 participants | 6 participants | 15 participants | 16 participants |
| Sex: Female, Male Female | 45 Participants | 9 Participants | 19 Participants | 17 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 17 | 0 / 9 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 17 / 19 | 11 / 17 | 6 / 9 | 3 / 4 | 3 / 4 |
| serious Total, serious adverse events | 2 / 19 | 1 / 17 | 0 / 9 | 0 / 4 | 0 / 4 |
Outcome results
Primary
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.
Time frame: Baseline; Week 12
Population: Treatment policy-estimand is the primary estimand for the primary endpoint analysis which involved participants in the Full Analysis Set (who were randomized and received at least one dose of study drug \[filgotinib, lanraplenib or placebo\]) with available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lanraplenib 30 mg | Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score From Baseline to Week 12 | -4.5 score on a scale | Standard Error 1.91 |
| Filgotinib 200 mg | Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score From Baseline to Week 12 | -8.7 score on a scale | Standard Error 1.85 |
| Placebo | Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score From Baseline to Week 12 | -5.5 score on a scale | Standard Error 2.56 |
p-value: 0.75Mixed-effect repeated measures model
p-value: 0.3047Mixed-effect repeated measures model
Secondary
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.
Time frame: Baseline; Week 12
Population: Participants in the Full Analysis Set were analyzed. Missing data are imputed as No Response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanraplenib 30 mg | Percentage of Participants at Week 12 With Decrease of ≥ 5 Points in CLASI Activity Score From Baseline | 47.4 Percentage of participants |
| Filgotinib 200 mg | Percentage of Participants at Week 12 With Decrease of ≥ 5 Points in CLASI Activity Score From Baseline | 64.7 Percentage of participants |
| Placebo | Percentage of Participants at Week 12 With Decrease of ≥ 5 Points in CLASI Activity Score From Baseline | 44.4 Percentage of participants |
p-value: 0.8869Cochran-Mantel-Haenszel
p-value: 0.3293Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline; Week 12
Population: Participants in the Full Analysis Set were analyzed. Missing data are imputed as No Response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanraplenib 30 mg | Percentage of Participants at Week 12 With No Worsening in CLASI Activity Score From Baseline | 84.2 Percentage of participants |
| Filgotinib 200 mg | Percentage of Participants at Week 12 With No Worsening in CLASI Activity Score From Baseline | 94.1 Percentage of participants |
| Placebo | Percentage of Participants at Week 12 With No Worsening in CLASI Activity Score From Baseline | 88.9 Percentage of participants |
p-value: 0.7456Cochran-Mantel-Haenszel
p-value: 0.6407Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set who were randomized to Filgotinib 200 mg or Lanraplenib 200 mg.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanraplenib 30 mg | Percentage of Participants at Week 24 With Decrease of ≥ 5 Points in CLASI Activity Score From Baseline | 50.0 Percentage of participants |
| Filgotinib 200 mg | Percentage of Participants at Week 24 With Decrease of ≥ 5 Points in CLASI Activity Score From Baseline | 83.3 Percentage of participants |
p-value: <0.0001One sample exact binomial test
p-value: <0.0001One sample exact binomial test
Secondary
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.
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set who were randomized to Filgotinib 200 mg or Lanraplenib 200 mg.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanraplenib 30 mg | Percentage of Participants at Week 24 With No Worsening in CLASI Activity Score From Baseline | 85.7 Percentage of participants |
| Filgotinib 200 mg | Percentage of Participants at Week 24 With No Worsening in CLASI Activity Score From Baseline | 100.0 Percentage of participants |
p-value: <0.0001One sample exact binomial test
p-value: <0.0001One sample exact binomial test