Rheumatoid Arthritis
Conditions
Brief summary
The primary objective of this study is to evaluate the long-term safety and tolerability of filgotinib in participants who have completed one of the parent studies of filgotinib in rheumatoid arthritis (RA).
Interventions
DRUGFilgotinib
Tablet(s) administered orally once daily
Tablet(s) administered orally once daily
Sponsors
Alfasigma S.p.A.
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This study was originally designed and initiated as a double-blind study but the study design will change to open-label following implementation of the protocol amendment # 4.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Males or females who may benefit from filgotinib as judged by the investigator AND who completed a Gilead sponsored filgotinib parent study for RA as outlined below: * Have completed GS-US-417-0301, GS-US-417-0302 or GS-US-417-0303 on study drug * OR * Have completed GS-US-417-0302 on standard of care therapy due to RA non-responder status * Females of childbearing potential must have a negative pregnancy test prior to first dose of study drug in the long term extension (LTE) * Females of childbearing potential who engage in heterosexual intercourse must agree to protocol-approved methods of contraception Key
Exclusion criteria
* Diagnosis of an autoimmune or inflammatory joint disease other than RA, which would put the participant at risk by participating in the study or would interfere with study assessments/data interpretation, per judgment of the investigator * Known hypersensitivity to the study drug or its excipients * Any medical condition which would put the participant at risk by participating in the study or would interfere with study assessments/data interpretation, per judgment of the investigator NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Day 1 to Week 376 (end of study) | An adverse event (AE) was any untoward medical occurrence in a clinical study participant after administration of an investigational product, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or significant medical event. A TEAE was any AE with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or premature discontinuation of study drug. |
| Number of Participants Who Reported Treatment-Emergent Graded Laboratory Abnormalities in Serum Chemistry Parameters | Day 1 to Week 376 (end of study) | Treatment-emergent laboratory abnormalities were defined as an increase of at least one toxicity grade from the LTE baseline at any post-baseline time point, up to and including 30 days after the last study drug dose for subjects who permanently discontinued treatment. Abnormalities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03, as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), and Grade 4 (life-threatening). Blood samples were collected by venipuncture in the arm at the specified time points. The laboratory values outside the normal range were flagged and the clinical relevance was determined by Medical Monitor and Clinical Investigators. |
| Number of Participants Who Reported Treatment-Emergent Graded Laboratory Abnormalities in Hematology Parameters | Day 1 to Week 376 (end of study) | Treatment-emergent laboratory abnormalities were defined as an increase of at least one toxicity grade from the LTE baseline at any post-baseline time point, up to and including 30 days after the last study drug dose for subjects who permanently discontinued treatment. Abnormalities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03, as Grade 1 (mild), Grade 2 (moderate), and Grade 3 (severe) and Grade 4 (life-threatening). Blood samples were collected by venipuncture in the arm at the specified time points. The laboratory values outside the normal range were flagged and the clinical relevance was determined by Medical Monitor and Clinical Investigators. |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Baseline and At Week 312 | SBP and DBP were collected at specified timepoints after participants had remained in a resting position for at least 5 minutes. The LTE baseline value was defined as the last available value collected on or prior to the date of the first dose of any study drug in the LTE. Change from the LTE baseline to a postbaseline visit was defined as the postbaseline value minus the LTE baseline value. |
| Change From Baseline in Pulse Rate | Baseline and At Week 312 | Pulse rate was collected at specified timepoints after participants had remained in a resting position for at least 5 minutes. The LTE baseline value was defined as the last available value collected on or prior to the date of the first dose of any study drug in the LTE. Change from the LTE baseline to a postbaseline visit was defined as the postbaseline value minus the LTE baseline value. |
| Change From Baseline in Respiration Rate | Baseline and At Week 312 | Changes in respiration rates were collected at specified timepoints after participants had remained in a resting position for at least 5 minutes. The LTE baseline value was defined as the last available value collected on or prior to the date of the first dose of any study drug in the LTE. Change from the LTE baseline to a postbaseline visit was defined as the postbaseline value minus the LTE baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved American College of Rheumatology (ACR) for 20, 50 and 70 | At Week 312 | ACR is the improvement from the parent study baseline in swollen joint count (66 joints) where joints were classified as swollen or not swollen, tender joint count (68) where scoring was performed on different aspects of tenderness, and improvement in 3 of 5 items: Subject pain assessment: pain score form Health Assessment Questionnaire Disability Index (HAQ-DI; scale 0=no difficulty to 3=unable to do) was calculated; Subject global assessment of disease activity: a horizontal visual analog scale (VAS; 0=best to 10=worst) was used to assess the participants arthritis status; Physicians global assessment of disease activity: A horizontal VAS (0=best to 10=worst) was used; Subject's assessment of physical function: HAQ-DI (scale 0=no difficulty to 3=unable to do) was used to calculate participants physical function and Acute-phase reactant value: C-reactive level protein is measured. ACR20, 50 and 70 responders were participants with at least 20%, 50% and 70% achievement respectively. |
Countries
Argentina, Australia, Belgium, Bulgaria, Canada, Chile, Czechia, France, Germany, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Malaysia, Mexico, New Zealand, Poland, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORAlfasigma Study Director
Alfasigma S.p.A.
Participant flow
Recruitment details
An open-label, multicenter, long-term extension study (LTE) that assessed safety and efficacy of filgotinib in participants with rheumatoid arthritis. Eligible participants from studies GS-US-417-0301(NCT02889796), GS-US-417-0302(NCT02873936), and GS-US-417-0303(NCT02886728) were enrolled. Participants who had received a fixed dose of filgotinib in the parent studies continued the same dosage, while those who had received placebo were randomized to receive either 100 mg or 200 mg of filgotinib.
Pre-assignment details
A total of 2731 participants were enrolled in the study of which 2729 participants received at least 1 dose of study drug. The study was considered completed because, 350 participants were discontinued from the study by sponsor only after following commercial availability of filgotinib to ensure continuous access to filgotinib therapy.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 221 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 265 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 192 Participants |
| Race (NIH/OMB) Asian | 186 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 1861 Participants |
| Sex: Female, Male Female | 2198 Participants |
| Sex: Female, Male Male | 235 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 | 45 / 1,195 | 6 / 335 | 26 / 863 | 13 / 336 |
| other Total, other adverse events | 1,071 / 1,195 | 300 / 335 | 769 / 863 | 283 / 336 |
| serious Total, serious adverse events | 288 / 1,195 | 74 / 335 | 212 / 863 | 87 / 336 |
Outcome results
None listed