Noninfectious Uveitis
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of filgotinib versus placebo for the treatment of the signs and symptoms of noninfectious uveitis as measured by the percentage of participants failing treatment for active noninfectious uveitis by Week 24.
Interventions
DRUGFilgotinib
Tablet(s) administered orally
Tablet(s) administered orally
DRUGPrednisone
Tablet(s) administered orally
Sponsors
Galapagos NV
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Is diagnosed with active noninfectious intermediate-, posterior-, or pan-uveitis * Must have active uveitic disease at the Day 1/Baseline visit as defined by the presence of at least 1 of the following parameters in at least one eye despite 2 weeks of maintenance therapy with oral prednisone (≥ 10 mg/day to ≤ 60 mg/day) or an oral corticosteroid equivalent: * Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion * ≥ 2+ anterior chamber cells per the Standardization of Uveitis Nomenclature (SUN) criteria * ≥ 2+ vitreous haze per the National Eye Institute/Standardization of Uveitis Nomenclature (NEI/SUN) criteria * No evidence of active tuberculosis (TB) or untreated latent TB Key
Exclusion criteria
* Participants with elevated intraocular pressures and/or severe glaucoma * Confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus (CMV), Human T-Lymphotropic Virus Type 1 (HTLV-1), Whipple's disease, Herpes Zoster virus (HZV), Lyme disease, toxoplasmosis and herpes simplex virus (HSV) Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Failing Treatment for Active NonInfectious Uveitis by Week 24 | Week 6 through Week 24 | Treatment failure was a participant meeting at least 1 of these criteria in at least 1 eye: New active, inflammatory lesions relative to Day 1/Baseline (all visits starting Week (Wk) 6); Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (change of Grade 0 to Grade 2+/Grade 0.5+ to Grade 3+) (all visits after Wk 6) relative to best state (RBS) achieved in Anterior Chamber (AC) cell grade (Standardization of Uveitis Nomenclature \[SUN\] criteria)\[AC cell grades range from 0 (0 cells) to 4+ (\>50 cells), higher scores=severe uveitis\]; Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (all visits after Wk 6) RBS achieved in Vitreous Haze (VH) grade (National Eye Institute \[NEI\]/SUN criteria)\[VH grades range from 0 (no evident VH) to 4+ (optic nerve head is obscured), higher scores=severe uveitis\]; Worsening of best corrected visual acuity (BCVA) by ≥15 letters RBS achieved (all visits starting Wk 6), measured by an eye chart, fewer correct letters=severe uveitis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Vitreous Haze (VH) Grade in Each Eye (NEI/SUN Criteria), From Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) Visit or Early Termination (ET) | Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks) | Grading of VH was based on the publication from the NEI which has also been adapted by the SUN working group. VH grades range from 0 (no evident VH) to 4+ (optic nerve head is obscured), with higher scores indicating greater severity of uveitis. A negative change from best state value obtained prior to Week 6 indicates improvement. |
| Change in Anterior Chamber (AC) Cell Grade in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks) | The number of AC cells observed within a 1 mm × 1 mm slit beam were recorded for each eye. The reported number was used to determine the grade according to the SUN criteria. AC cell grades range from 0 (0 cells in field) to 4+ (\>50 cells in field), with higher scores indicating more cells visible in the AC and greater severity of uveitis. A negative change from best state value obtained prior to Week 6 indicates improvement. |
| Change in Logarithm of the Minimal Angle of Resolution (logMAR) Best Corrected Visual Acuity (BCVA) in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks) | BCVA is the best possible vision that an eye can achieve with the set of glasses or contact lenses. A refraction test was performed to measure the appropriate lens strength to focus light on the retina. Using the appropriate corrective lenses based on that visit's refraction, participant's BCVA was measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. In the ETDRS system, 15 letters is equal to a change in 3 lines of visual acuity. If the participant is unable to read letters on a testing chart, visual acuity is described as ranging from ability to count fingers, recognize hand movements, or light perception. The smaller BVCA score indicates greater severity of uveitis. A positive change from best state value obtained prior to Week 6 indicates improvement. |
| Time to Treatment Failure on or After Week 6 | Week 6 through Week 52 | Treatment failure was a participant meeting at least 1 of these criteria in at least 1 eye: New active, inflammatory lesions relative to Day 1/Baseline (all visits starting Wk 6); Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (change of Grade 0 to Grade 2+/Grade 0.5+ to Grade 3+) (all visits after Wk 6) relative to best state (RBS) achieved in AC cell grade (SUN criteria) \[AC cell grades range from 0 (0 cells) to 4+ (\>50 cells), higher scores=severe uveitis\]; Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (all visits after Wk 6) RBS achieved in VH grade (NEI/SUN criteria) \[VH grades range from 0 (no evident VH) to 4+ (optic nerve head is obscured), higher scores=severe uveitis\]; Worsening of BCVA by ≥15 letters RBS achieved (all visits starting Wk 6), measured by an eye chart, fewer correct letters=severe uveitis. |
| Time to Development of Macular Edema in At Least One Eye on or After Week 6 | Week 6 through Week 52 | Time in weeks until the development of Macular edema or Week 52 or EOT or ET. Macular edema is determined by OCT and is defined as central retinal thickness ≥ 300 microns if using Cirrus machine, or ≥ 315 microns if using Spectralis machine. |
| Plasma Concentration of Filgotinib | Day 1 post dose, Weeks 4 and 6 predose, Week 12 post dose, Weeks 24, 36, 52 (EOT), ET at any time | — |
| Plasma Concentration of Metabolite, GS-829845 | Day 1 post dose, Weeks 4 and 6 predose, Week 12 post dose, Weeks 24, 36, 52 (EOT), ET at any time | — |
| Log Change in Central Retinal Thickness in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks) | Central retinal thickness is measured by optical coherence tomography (OCT). Central retinal thickness is defined as the thickness of the retina in the center of the foveal pit (1 mm subfield). The larger central retinal thickness value indicates greater severity of uveitis. A negative change from best state value obtained prior to Week 6 indicates improvement. |
Countries
Australia, Canada, Germany, Israel, New Zealand, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States, the United Kingdom, Canada, Australia, Germany, Israel, and New Zealand. The first participant was screened on 26 July 2017. The last study visit occurred on 22 April 2021.
Pre-assignment details
116 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Filgotinib Participants received filgotinib 200 mg tablet orally, once daily for up to 52 weeks along with a standardized prednisone burst of 60 mg/day at Day 1/Baseline followed by a protocol-defined mandatory taper schedule up to Week 15. | 37 |
| Placebo Participants received placebo to match filgotinib tablet orally, once daily for up to 52 weeks along with a standardized prednisone burst of 60 mg/day at Day 1/Baseline followed by a protocol-defined mandatory taper schedule up to Week 15. | 35 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Investigator's Discretion | 1 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Pregnancy/Partner Pregnancy | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | Filgotinib |
|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 15.5 | 43 years STANDARD_DEVIATION 15.7 | 48 years STANDARD_DEVIATION 15.1 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 14 Participants | 10 Participants | 4 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 57 Participants | 25 Participants | 32 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Black or African American | 10 Participants | 8 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 55 Participants | 26 Participants | 29 Participants |
| Region of Enrollment Australia | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Canada | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Germany | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Israel | 1 participants | 1 participants | 0 participants |
| Region of Enrollment New Zealand | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United Kingdom | 6 participants | 2 participants | 4 participants |
| Region of Enrollment United States | 60 participants | 31 participants | 29 participants |
| Sex: Female, Male Female | 43 Participants | 20 Participants | 23 Participants |
| Sex: Female, Male Male | 29 Participants | 15 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 36 |
| other Total, other adverse events | 28 / 37 | 19 / 35 |
| serious Total, serious adverse events | 5 / 37 | 2 / 35 |
Outcome results
Primary
Percentage of Participants Failing Treatment for Active NonInfectious Uveitis by Week 24
Treatment failure was a participant meeting at least 1 of these criteria in at least 1 eye: New active, inflammatory lesions relative to Day 1/Baseline (all visits starting Week (Wk) 6); Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (change of Grade 0 to Grade 2+/Grade 0.5+ to Grade 3+) (all visits after Wk 6) relative to best state (RBS) achieved in Anterior Chamber (AC) cell grade (Standardization of Uveitis Nomenclature \[SUN\] criteria)\[AC cell grades range from 0 (0 cells) to 4+ (\>50 cells), higher scores=severe uveitis\]; Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (all visits after Wk 6) RBS achieved in Vitreous Haze (VH) grade (National Eye Institute \[NEI\]/SUN criteria)\[VH grades range from 0 (no evident VH) to 4+ (optic nerve head is obscured), higher scores=severe uveitis\]; Worsening of best corrected visual acuity (BCVA) by ≥15 letters RBS achieved (all visits starting Wk 6), measured by an eye chart, fewer correct letters=severe uveitis.
Time frame: Week 6 through Week 24
Population: Evaluable Analysis Set included all randomized participants who received at least one dose of study drug and did not permanently discontinue from the study prior to Week 6.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib | Percentage of Participants Failing Treatment for Active NonInfectious Uveitis by Week 24 | 37.5 percentage of participants |
| Placebo | Percentage of Participants Failing Treatment for Active NonInfectious Uveitis by Week 24 | 67.6 percentage of participants |
p-value: 0.006495% CI: [-56.2, -4.1]Cochran-Mantel-Haenszel
Secondary
Change in Anterior Chamber (AC) Cell Grade in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET
The number of AC cells observed within a 1 mm × 1 mm slit beam were recorded for each eye. The reported number was used to determine the grade according to the SUN criteria. AC cell grades range from 0 (0 cells in field) to 4+ (\>50 cells in field), with higher scores indicating more cells visible in the AC and greater severity of uveitis. A negative change from best state value obtained prior to Week 6 indicates improvement.
Time frame: Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Population: Participants in the Evaluable Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Filgotinib | Change in Anterior Chamber (AC) Cell Grade in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Best State Prior to Week 6 | 0.0 score | Standard Deviation 0.09 |
| Filgotinib | Change in Anterior Chamber (AC) Cell Grade in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Best State Prior to Week 6 | 0.0 score | Standard Deviation 0.12 |
| Filgotinib | Change in Anterior Chamber (AC) Cell Grade in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Change From Best State at Week 52/EOT/ET | 0.2 score | Standard Deviation 0.59 |
| Filgotinib | Change in Anterior Chamber (AC) Cell Grade in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Change From Best State at Week 52/EOT/ET | 0.2 score | Standard Deviation 0.53 |
| Placebo | Change in Anterior Chamber (AC) Cell Grade in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Change From Best State at Week 52/EOT/ET | 0.7 score | Standard Deviation 1.05 |
| Placebo | Change in Anterior Chamber (AC) Cell Grade in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Best State Prior to Week 6 | 0.1 score | Standard Deviation 0.19 |
| Placebo | Change in Anterior Chamber (AC) Cell Grade in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Change From Best State at Week 52/EOT/ET | 0.6 score | Standard Deviation 0.87 |
| Placebo | Change in Anterior Chamber (AC) Cell Grade in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Best State Prior to Week 6 | 0.1 score | Standard Deviation 0.25 |
p-value: 0.014595% CI: [-0.8, -0.1]Repeated Measure ANCOVA
Secondary
Change in Logarithm of the Minimal Angle of Resolution (logMAR) Best Corrected Visual Acuity (BCVA) in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET
BCVA is the best possible vision that an eye can achieve with the set of glasses or contact lenses. A refraction test was performed to measure the appropriate lens strength to focus light on the retina. Using the appropriate corrective lenses based on that visit's refraction, participant's BCVA was measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. In the ETDRS system, 15 letters is equal to a change in 3 lines of visual acuity. If the participant is unable to read letters on a testing chart, visual acuity is described as ranging from ability to count fingers, recognize hand movements, or light perception. The smaller BVCA score indicates greater severity of uveitis. A positive change from best state value obtained prior to Week 6 indicates improvement.
Time frame: Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Population: Participants in the Evaluable Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Filgotinib | Change in Logarithm of the Minimal Angle of Resolution (logMAR) Best Corrected Visual Acuity (BCVA) in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Best State Prior to Week 6 | 0.09 logMAR | Standard Deviation 0.195 |
| Filgotinib | Change in Logarithm of the Minimal Angle of Resolution (logMAR) Best Corrected Visual Acuity (BCVA) in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Best State Prior to Week 6 | 0.09 logMAR | Standard Deviation 0.193 |
| Filgotinib | Change in Logarithm of the Minimal Angle of Resolution (logMAR) Best Corrected Visual Acuity (BCVA) in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Change From Best State at Week 52/EOT/ET | 0.03 logMAR | Standard Deviation 0.154 |
| Filgotinib | Change in Logarithm of the Minimal Angle of Resolution (logMAR) Best Corrected Visual Acuity (BCVA) in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Change From Best State at Week 52/EOT/ET | -0.01 logMAR | Standard Deviation 0.116 |
| Placebo | Change in Logarithm of the Minimal Angle of Resolution (logMAR) Best Corrected Visual Acuity (BCVA) in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Change From Best State at Week 52/EOT/ET | 0.07 logMAR | Standard Deviation 0.144 |
| Placebo | Change in Logarithm of the Minimal Angle of Resolution (logMAR) Best Corrected Visual Acuity (BCVA) in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Best State Prior to Week 6 | 0.07 logMAR | Standard Deviation 0.209 |
| Placebo | Change in Logarithm of the Minimal Angle of Resolution (logMAR) Best Corrected Visual Acuity (BCVA) in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Change From Best State at Week 52/EOT/ET | 0.05 logMAR | Standard Deviation 0.112 |
| Placebo | Change in Logarithm of the Minimal Angle of Resolution (logMAR) Best Corrected Visual Acuity (BCVA) in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Best State Prior to Week 6 | 0.12 logMAR | Standard Deviation 0.28 |
p-value: 0.038995% CI: [-0.1, 0]Repeated Measure ANCOVA
Secondary
Change in Vitreous Haze (VH) Grade in Each Eye (NEI/SUN Criteria), From Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) Visit or Early Termination (ET)
Grading of VH was based on the publication from the NEI which has also been adapted by the SUN working group. VH grades range from 0 (no evident VH) to 4+ (optic nerve head is obscured), with higher scores indicating greater severity of uveitis. A negative change from best state value obtained prior to Week 6 indicates improvement.
Time frame: Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Population: Participants in the Evaluable Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Filgotinib | Change in Vitreous Haze (VH) Grade in Each Eye (NEI/SUN Criteria), From Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) Visit or Early Termination (ET) | Left Eye: Change From Best State at Week 52/EOT/ET | 0.1 score | Standard Deviation 0.79 |
| Filgotinib | Change in Vitreous Haze (VH) Grade in Each Eye (NEI/SUN Criteria), From Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) Visit or Early Termination (ET) | Left Eye: Best State Prior to Week 6 | 0.3 score | Standard Deviation 0.4 |
| Filgotinib | Change in Vitreous Haze (VH) Grade in Each Eye (NEI/SUN Criteria), From Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) Visit or Early Termination (ET) | Right Eye: Change From Best State at Week 52/EOT/ET | 0.1 score | Standard Deviation 0.62 |
| Filgotinib | Change in Vitreous Haze (VH) Grade in Each Eye (NEI/SUN Criteria), From Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) Visit or Early Termination (ET) | Right Eye: Best State Prior to Week 6 | 0.3 score | Standard Deviation 0.36 |
| Placebo | Change in Vitreous Haze (VH) Grade in Each Eye (NEI/SUN Criteria), From Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) Visit or Early Termination (ET) | Right Eye: Change From Best State at Week 52/EOT/ET | 0.2 score | Standard Deviation 0.66 |
| Placebo | Change in Vitreous Haze (VH) Grade in Each Eye (NEI/SUN Criteria), From Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) Visit or Early Termination (ET) | Left Eye: Change From Best State at Week 52/EOT/ET | 0.3 score | Standard Deviation 0.75 |
| Placebo | Change in Vitreous Haze (VH) Grade in Each Eye (NEI/SUN Criteria), From Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) Visit or Early Termination (ET) | Right Eye: Best State Prior to Week 6 | 0.3 score | Standard Deviation 0.45 |
| Placebo | Change in Vitreous Haze (VH) Grade in Each Eye (NEI/SUN Criteria), From Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) Visit or Early Termination (ET) | Left Eye: Best State Prior to Week 6 | 0.2 score | Standard Deviation 0.33 |
p-value: 0.35595% CI: [-0.4, 0.2]Repeated Measure ANCOVA
Secondary
Log Change in Central Retinal Thickness in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET
Central retinal thickness is measured by optical coherence tomography (OCT). Central retinal thickness is defined as the thickness of the retina in the center of the foveal pit (1 mm subfield). The larger central retinal thickness value indicates greater severity of uveitis. A negative change from best state value obtained prior to Week 6 indicates improvement.
Time frame: Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Population: Participants in the Evaluable Analysis Set with the available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Filgotinib | Log Change in Central Retinal Thickness in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Best State Prior to Week 6 | 2.45 log microns | Standard Deviation 0.059 |
| Filgotinib | Log Change in Central Retinal Thickness in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Best State Prior to Week 6 | 2.47 log microns | Standard Deviation 0.056 |
| Filgotinib | Log Change in Central Retinal Thickness in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Change From Best State at Week 52/EOT/ET | 0.01 log microns | Standard Deviation 0.062 |
| Filgotinib | Log Change in Central Retinal Thickness in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Change From Best State at Week 52/EOT/ET | 0.01 log microns | Standard Deviation 0.049 |
| Placebo | Log Change in Central Retinal Thickness in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Change From Best State at Week 52/EOT/ET | 0.03 log microns | Standard Deviation 0.055 |
| Placebo | Log Change in Central Retinal Thickness in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Best State Prior to Week 6 | 2.46 log microns | Standard Deviation 0.097 |
| Placebo | Log Change in Central Retinal Thickness in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Left Eye: Change From Best State at Week 52/EOT/ET | 0.04 log microns | Standard Deviation 0.08 |
| Placebo | Log Change in Central Retinal Thickness in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET | Right Eye: Best State Prior to Week 6 | 2.44 log microns | Standard Deviation 0.104 |
p-value: 0.03495% CI: [-0.05, 0]Repeated Measure ANCOVA
Secondary
Plasma Concentration of Filgotinib
Time frame: Day 1 post dose, Weeks 4 and 6 predose, Week 12 post dose, Weeks 24, 36, 52 (EOT), ET at any time
Population: Participants in the Safety Analysis Set who have at least one non-missing concentration data with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Filgotinib | Plasma Concentration of Filgotinib | Day 1 Postdose | 748.5 nanograms per millilitre (ng/ml) | Standard Deviation 1043.84 |
| Filgotinib | Plasma Concentration of Filgotinib | Week 4 Predose | 173.3 nanograms per millilitre (ng/ml) | Standard Deviation 364.46 |
| Filgotinib | Plasma Concentration of Filgotinib | Week 6 Predose | 133.9 nanograms per millilitre (ng/ml) | Standard Deviation 306.18 |
| Filgotinib | Plasma Concentration of Filgotinib | Week 12 Postdose | 1088.7 nanograms per millilitre (ng/ml) | Standard Deviation 856.57 |
| Filgotinib | Plasma Concentration of Filgotinib | Week 24 Single Anytime | 397.5 nanograms per millilitre (ng/ml) | Standard Deviation 561.57 |
| Filgotinib | Plasma Concentration of Filgotinib | Week 36 Single Anytime | 295.7 nanograms per millilitre (ng/ml) | Standard Deviation 420.25 |
| Filgotinib | Plasma Concentration of Filgotinib | Week 52 Single Anytime | 195.2 nanograms per millilitre (ng/ml) | Standard Deviation 344.54 |
| Filgotinib | Plasma Concentration of Filgotinib | Early Termination Single Anytime | 434.8 nanograms per millilitre (ng/ml) | Standard Deviation 478.72 |
Secondary
Plasma Concentration of Metabolite, GS-829845
Time frame: Day 1 post dose, Weeks 4 and 6 predose, Week 12 post dose, Weeks 24, 36, 52 (EOT), ET at any time
Population: Participants in the Safety Analysis Set who have at least one non-missing concentration data with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Filgotinib | Plasma Concentration of Metabolite, GS-829845 | Early Termination Single Anytime | 2171.0 ng/ml | Standard Deviation 1224.77 |
| Filgotinib | Plasma Concentration of Metabolite, GS-829845 | Day 1 Postdose | 230.8 ng/ml | Standard Deviation 317.98 |
| Filgotinib | Plasma Concentration of Metabolite, GS-829845 | Week 4 Predose | 2085.6 ng/ml | Standard Deviation 924.91 |
| Filgotinib | Plasma Concentration of Metabolite, GS-829845 | Week 6 Predose | 2107.7 ng/ml | Standard Deviation 749.28 |
| Filgotinib | Plasma Concentration of Metabolite, GS-829845 | Week 12 Postdose | 3237.0 ng/ml | Standard Deviation 1180.74 |
| Filgotinib | Plasma Concentration of Metabolite, GS-829845 | Week 24 Single Anytime | 3478.1 ng/ml | Standard Deviation 1137.63 |
| Filgotinib | Plasma Concentration of Metabolite, GS-829845 | Week 36 Single Anytime | 2944.3 ng/ml | Standard Deviation 1130.84 |
| Filgotinib | Plasma Concentration of Metabolite, GS-829845 | Week 52 Single Anytime | 2510.7 ng/ml | Standard Deviation 1732.59 |
Secondary
Time to Development of Macular Edema in At Least One Eye on or After Week 6
Time in weeks until the development of Macular edema or Week 52 or EOT or ET. Macular edema is determined by OCT and is defined as central retinal thickness ≥ 300 microns if using Cirrus machine, or ≥ 315 microns if using Spectralis machine.
Time frame: Week 6 through Week 52
Population: Participants in the Evaluable Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Time to Development of Macular Edema in At Least One Eye on or After Week 6 | 7.8 weeks |
| Placebo | Time to Development of Macular Edema in At Least One Eye on or After Week 6 | 12.3 weeks |
p-value: 0.589395% CI: [0.625, 2.277]Stratified Log-Rank Test
Secondary
Time to Treatment Failure on or After Week 6
Treatment failure was a participant meeting at least 1 of these criteria in at least 1 eye: New active, inflammatory lesions relative to Day 1/Baseline (all visits starting Wk 6); Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (change of Grade 0 to Grade 2+/Grade 0.5+ to Grade 3+) (all visits after Wk 6) relative to best state (RBS) achieved in AC cell grade (SUN criteria) \[AC cell grades range from 0 (0 cells) to 4+ (\>50 cells), higher scores=severe uveitis\]; Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (all visits after Wk 6) RBS achieved in VH grade (NEI/SUN criteria) \[VH grades range from 0 (no evident VH) to 4+ (optic nerve head is obscured), higher scores=severe uveitis\]; Worsening of BCVA by ≥15 letters RBS achieved (all visits starting Wk 6), measured by an eye chart, fewer correct letters=severe uveitis.
Time frame: Week 6 through Week 52
Population: Participants in the Evaluable Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Time to Treatment Failure on or After Week 6 | NA weeks |
| Placebo | Time to Treatment Failure on or After Week 6 | 22.0 weeks |
p-value: 0.001495% CI: [0.144, 0.663]Stratified Log-Rank Test