Rheumatoid Arthritis
Conditions
Brief summary
The primary objective of this study is to evaluate the effect of GS-9876 versus placebo for the treatment of signs and symptoms of rheumatoid arthritis (RA) in participants with active RA as measured by change from baseline in Disease Activity Score for 28 joint count using C-reactive protein (CRP) (DAS28 (CRP)) at Week 12.
Interventions
DRUGGS-9876
One tablet administered orally once daily
DRUGFilgotinib
Two tablets administered orally once daily
DRUGGS-9876 placebo
One tablet administered orally once daily
Two tablets administered orally once daily
DRUGMethotrexate
Background therapy with methotrexate administered orally or parenterally once weekly
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: * Active RA disease as defined by: a tender joint count (TJC) of ≥ 6 (out of 68), a swollen joint count (SJC) of ≥ 6 (out of 66) at screening and Day 1 * Inadequate response to treatment with oral or parenteral methotrexate (MTX) 7.5 to 25 mg/week continuously for at least 12 weeks * No evidence of active or latent tuberculosis Key
Exclusion criteria
* Prior treatment with B-cell depleting agents (eg, rituximab), unless more than 6 months prior to the first dose of study drug and documented return of CD19+ cells at screening * Prior treatment with any commercially available or investigational spleen tyrosine kinase (SYK) inhibitor * Concurrent treatment with any other conventional synthetic DMARD (csDMARD) other than MTX and/or hydroxychloroquine (HCQ) (prior csDMARD treatment allowed if appropriate wash out as defined in the protocol) * Concurrent treatment with any biological disease modifying anti-rheumatic drug (bDMARD)(prior bDMARD treatment allowed if appropriate wash out as defined in the protocol). Prior failure to treatment with bDMARDs is not an exclusion criterion. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Disease Activity Score 28 C-Reactive Protein (DAS28 (CRP)) at Week 12 | Baseline; Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved American College of Rheumatology (ACR)20 Improvement at Week 12 | Week 12 | American College of Rheumatology (ACR)20 response was defined as having ≥ 20% improvement from baseline in the number of tender and the number of swollen joints, and a 20% improvement in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity (PhGA), Participant's Global Assessment of Disease Activity (PtGA), Participant's pain assessment, Participant's assessment of physical function (HAQ-DI) score, and C-reactive protein (CRP). |
| Percentage of Participants Who Achieved ACR50 Improvement at Week 12 | Week 12 | ACR50 response was defined as having ≥ 50% improvement from baseline in the number of tender and the number of swollen joints, and a 50% improvement in at least 3 of the following 5 criteria: PhGA, PtGA, Participant's pain assessment, HAQ-DI score, and CRP. |
| Percentage of Participants Who Achieved ACR70 Improvement at Week 12 | Week 12 | ACR70 response was defined as having ≥ 70% improvement from baseline in the number of tender and the number of swollen joints, and a 70% improvement in at least 3 of the following 5 criteria: PhGA, PtGA, Participant's pain assessment, HAQ-DI score, and CRP. |
| Change From Baseline in The Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12 | Baseline; Week 12 | The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a self-reported tool used to assess the ability to perform tasks in 8 functional categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Responses in each functional category were collected as 0 (without any difficulty) to 3 (unable to do a task in that area). The HAQ-DI score ranges from 0 (no disability) to 3 (completely disabled), when 6 or more categories are non-missing. |
Countries
Bulgaria, Czechia, Georgia, Moldova, Poland, Ukraine, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States and Europe. The first participant was screened on 21 September 2016. The last study visit occurred on 20 September 2017.
Pre-assignment details
140 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| GS-9876 30 mg GS-9876 30 mg tablet orally once daily + filgotinib placebo 2 tablets orally once daily for 12 weeks and background therapy with methotrexate orally or parenterally once weekly | 20 |
| GS-9876 10 mg GS-9876 10 mg tablet orally once daily + filgotinib placebo 2 tablets orally once daily for 12 weeks and background therapy with methotrexate orally or parenterally once weekly | 20 |
| Filgotinib Filgotinib 2 x 100 mg tablet orally once daily + GS-9876 placebo tablet orally once daily for 12 weeks and background therapy with methotrexate orally or parenterally once weekly | 21 |
| Placebo GS-9876 placebo tablet orally once daily + filgotinib placebo 2 tablets orally once daily for 12 weeks and background therapy with methotrexate orally or parenterally once weekly | 22 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Investigator's Discretion | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Filgotinib | GS-9876 30 mg | Placebo | GS-9876 10 mg |
|---|---|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 11.5 | 53 years STANDARD_DEVIATION 15.4 | 58 years STANDARD_DEVIATION 7 | 54 years STANDARD_DEVIATION 10.9 | 56 years STANDARD_DEVIATION 11.4 |
| Disease Activity Score 28 C-Reactive Protein (DAS28 CRP) | 5.75 units on a scale STANDARD_DEVIATION 0.961 | 6.09 units on a scale STANDARD_DEVIATION 1.112 | 5.78 units on a scale STANDARD_DEVIATION 0.691 | 5.51 units on a scale STANDARD_DEVIATION 1.003 | 5.65 units on a scale STANDARD_DEVIATION 0.941 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 79 Participants | 19 Participants | 19 Participants | 22 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Health Assessment Questionnaire Disease Index (HAQ-DI) | 1.49 units on a scale STANDARD_DEVIATION 0.563 | 1.61 units on a scale STANDARD_DEVIATION 0.591 | 1.38 units on a scale STANDARD_DEVIATION 0.65 | 1.51 units on a scale STANDARD_DEVIATION 0.577 | 1.47 units on a scale STANDARD_DEVIATION 0.425 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 00 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 77 Participants | 21 Participants | 20 Participants | 19 Participants | 17 Participants |
| Region of Enrollment Bulgaria | 7 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Czechia | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Georgia | 10 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Moldova | 18 Participants | 6 Participants | 3 Participants | 4 Participants | 5 Participants |
| Region of Enrollment Poland | 6 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment Ukraine | 6 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 33 Participants | 8 Participants | 8 Participants | 9 Participants | 8 Participants |
| Sex: Female, Male Female | 69 Participants | 17 Participants | 15 Participants | 21 Participants | 16 Participants |
| Sex: Female, Male Male | 14 Participants | 4 Participants | 5 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 21 | 0 / 22 |
| other Total, other adverse events | 7 / 20 | 8 / 20 | 4 / 21 | 1 / 22 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 21 | 0 / 22 |
Outcome results
Primary
Change From Baseline in Disease Activity Score 28 C-Reactive Protein (DAS28 (CRP)) at Week 12
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.
Time frame: Baseline; Week 12
Population: Participants in the Full Analysis Set (participants who received at least 1 dose of study drug) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GS-9876 30 mg | Change From Baseline in Disease Activity Score 28 C-Reactive Protein (DAS28 (CRP)) at Week 12 | -1.26 units on a scale | Standard Deviation 1.276 |
| GS-9876 10 mg | Change From Baseline in Disease Activity Score 28 C-Reactive Protein (DAS28 (CRP)) at Week 12 | -0.78 units on a scale | Standard Deviation 1.119 |
| Filgotinib | Change From Baseline in Disease Activity Score 28 C-Reactive Protein (DAS28 (CRP)) at Week 12 | -2.46 units on a scale | Standard Deviation 1.242 |
| Placebo | Change From Baseline in Disease Activity Score 28 C-Reactive Protein (DAS28 (CRP)) at Week 12 | -1.36 units on a scale | Standard Deviation 1.044 |
p-value: 0.978Cochran-Mantel-Haenszel
p-value: 0.3Cochran-Mantel-Haenszel
p-value: 0.002Cochran-Mantel-Haenszel
Secondary
Change From Baseline in The Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a self-reported tool used to assess the ability to perform tasks in 8 functional categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Responses in each functional category were collected as 0 (without any difficulty) to 3 (unable to do a task in that area). The HAQ-DI score ranges from 0 (no disability) to 3 (completely disabled), when 6 or more categories are non-missing.
Time frame: Baseline; Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GS-9876 30 mg | Change From Baseline in The Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12 | -0.46 units on a scale | Standard Deviation 0.48 |
| GS-9876 10 mg | Change From Baseline in The Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12 | -0.18 units on a scale | Standard Deviation 0.8 |
| Filgotinib | Change From Baseline in The Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12 | -0.70 units on a scale | Standard Deviation 0.649 |
| Placebo | Change From Baseline in The Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12 | -0.39 units on a scale | Standard Deviation 0.389 |
p-value: 0.52895% CI: [-0.49, 0.25]Cochran-Mantel-Haenszel
p-value: 0.29395% CI: [-0.17, 0.57]Cochran-Mantel-Haenszel
p-value: 0.07295% CI: [-0.7, 0.03]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved ACR50 Improvement at Week 12
ACR50 response was defined as having ≥ 50% improvement from baseline in the number of tender and the number of swollen joints, and a 50% improvement in at least 3 of the following 5 criteria: PhGA, PtGA, Participant's pain assessment, HAQ-DI score, and CRP.
Time frame: Week 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GS-9876 30 mg | Percentage of Participants Who Achieved ACR50 Improvement at Week 12 | 20.0 percentage of participants |
| GS-9876 10 mg | Percentage of Participants Who Achieved ACR50 Improvement at Week 12 | 20.0 percentage of participants |
| Filgotinib | Percentage of Participants Who Achieved ACR50 Improvement at Week 12 | 47.6 percentage of participants |
| Placebo | Percentage of Participants Who Achieved ACR50 Improvement at Week 12 | 22.7 percentage of participants |
p-value: 0.85395% CI: [-32, 27.5]Cochran-Mantel-Haenszel
p-value: 0.85295% CI: [-32, 27.5]Cochran-Mantel-Haenszel
p-value: 0.09295% CI: [-6.6, 51.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved ACR70 Improvement at Week 12
ACR70 response was defined as having ≥ 70% improvement from baseline in the number of tender and the number of swollen joints, and a 70% improvement in at least 3 of the following 5 criteria: PhGA, PtGA, Participant's pain assessment, HAQ-DI score, and CRP.
Time frame: Week 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GS-9876 30 mg | Percentage of Participants Who Achieved ACR70 Improvement at Week 12 | 5.0 percentage of participants |
| GS-9876 10 mg | Percentage of Participants Who Achieved ACR70 Improvement at Week 12 | 15.0 percentage of participants |
| Filgotinib | Percentage of Participants Who Achieved ACR70 Improvement at Week 12 | 38.1 percentage of participants |
| Placebo | Percentage of Participants Who Achieved ACR70 Improvement at Week 12 | 13.6 percentage of participants |
p-value: 0.3695% CI: [-37.9, 22.5]Cochran-Mantel-Haenszel
p-value: 0.89695% CI: [-28, 31.7]Cochran-Mantel-Haenszel
p-value: 0.07295% CI: [-6.6, 50.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved American College of Rheumatology (ACR)20 Improvement at Week 12
American College of Rheumatology (ACR)20 response was defined as having ≥ 20% improvement from baseline in the number of tender and the number of swollen joints, and a 20% improvement in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity (PhGA), Participant's Global Assessment of Disease Activity (PtGA), Participant's pain assessment, Participant's assessment of physical function (HAQ-DI) score, and C-reactive protein (CRP).
Time frame: Week 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GS-9876 30 mg | Percentage of Participants Who Achieved American College of Rheumatology (ACR)20 Improvement at Week 12 | 35.0 percentage of participants |
| GS-9876 10 mg | Percentage of Participants Who Achieved American College of Rheumatology (ACR)20 Improvement at Week 12 | 25.0 percentage of participants |
| Filgotinib | Percentage of Participants Who Achieved American College of Rheumatology (ACR)20 Improvement at Week 12 | 81.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved American College of Rheumatology (ACR)20 Improvement at Week 12 | 40.9 percentage of participants |
p-value: 0.6695% CI: [-36, 24]Cochran-Mantel-Haenszel
p-value: 0.27795% CI: [-44.7, 13.8]Cochran-Mantel-Haenszel
p-value: 0.00995% CI: [10.7, 65.6]Cochran-Mantel-Haenszel