Ulcerative Colitis
Conditions
Brief summary
Participants who were in clinical remission on 200 milligram (mg) filgotinib once daily for at least 2 consecutive quarterly visits in the ongoing SELECTION-LTE study (GS-US-418-3899, NCT02914535), were planned to be rolled over and randomized in this study. The primary objective of this study was to evaluate the efficacy of filgotinib in participants in stable clinical remission on 200 mg filgotinib once daily for whom the dose was decreased to 100 mg once daily compared to participants remaining on 200 mg once daily.
Detailed description
Participants were planned to receive the blinded treatment until primary analysis time point. After unblinding at the study primary analysis time point, participants would have received unblinded treatment. The clinical trial was originally designed with the primary endpoint to be assessed at Week 48. Due to early termination of the study, none of the participants completed 48 weeks of treatment. All participants participated in blinded treatment period only and the study was unblinded globally after study completion.
Interventions
DRUGFilgotinib
Administered orally once daily
DRUGPlacebo
Administered orally once daily
Sponsors
Galapagos NV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study was double-blinded to treatment assignment until the last subject has reached the primary analysis time point.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants must have participated in the SELECTION-LTE study (GS-US-418-3899), who were on 200 mg filgotinib once daily and fulfilled the following conditions: * partial Mayo Clinical Score remission over a period of at least 2 consecutive quarterly visits in the SELECTION-LTE study (GS-US-418-3899) prior to screening of the present study; * free of corticosteroids for at least 12 weeks prior to and including baseline; * fecal calprotectin (FCP) ≤250 microgram per gram (μg/g) at last observation within 6 months prior to screening or FCP ≤250 μg/g during the screening of the present study. * sigmoidoscopy ES of 0 or 1 (local score) at screening. * Willing to refrain from live attenuated vaccines during the study and for 12 weeks after the last dose of filgotinib in the study. * Female participants of childbearing potential must have had a negative highly sensitive (serum beta human chorionic gonadotropin) pregnancy test during screening and must have agreed to continued monthly urine dipstick pregnancy testing during filgotinib treatment. * Female participants of childbearing potential must have agreed to use highly effective contraception measures as defined in the protocol. Key
Exclusion criteria
* Any chronic medical condition (including but not limited to, cardiac or pulmonary disease, alcohol, or drug abuse) that, in the opinion of the investigator or sponsor, would make the participant unsuitable for the study or would prevent compliance with the study protocol. * Participant had a known hypersensitivity to filgotinib ingredients or history of a significant allergic reaction to filgotinib ingredients as determined by the investigator. * Female participant who was pregnant or breastfeeding, or intended to become pregnant or breastfeed, and/or plans to undergo egg donation or egg harvesting for the purpose of current or future fertilization, during the study and until the end of the study. * Participant was unable or unwilling to comply with restrictions regarding prior and concomitant medication as described in the protocol. * Participant had a positive QuantiFERON® tuberculosis (TB) test at screening or had 2 indeterminate QuantiFERON® TB test results that required Investigational product (IP) treatment interruption, or participant had sign and symptoms of TB reactivation at screening. * History of malignancy during or in the last 5 years prior to participation in the UC parent studies, except for participants who had been successfully treated for nonmelanoma skin cancer or cervical carcinoma in situ. * Participant met discontinuation criteria of the SELECTION-LTE study (GS-US-418-3899). NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Corticosteroid-free Clinical Remission Based on Modified Mayo Clinical Score (mMCS) | Week 48 | The mMCS is a tool designed to measure disease activity for ulcerative colitis. The mMCS was calculated as the sum of the 3 subscores: stool frequency, rectal bleeding, and endoscopy. Each subscore was graded from 0 to 3 with higher scores indicating more severe disease activity. The total mMCS score ranged from 0 to 9 with higher scores indicating more severe disease activity. The mMCS remission was defined as a total score of score ≤2, with endoscopic subscore of ≤1, stool frequency subscore of ≤1, and a rectal bleeding subscore of 0. Corticosteroid-free mMCS remission was defined as being free of corticosteroids for at least 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to ES-Confirmed UC Flare | Baseline up to Week 48 | An ES-confirmed UC flare was defined as an increase in rectal bleeding subscore by at least 1 point and an increase in stool frequency subscore by at least 2 points and an increase in endoscopic subscore by at least 1 point. Each subscore graded from 0 to 3 with higher scores indicating more severe disease. |
| Change From Baseline in C-Reactive Protein (CRP) | Baseline, Week 4, Week 12, Week 24, Week 36, and Week 48 | CRP is an acute-phase protein which provides an objective criterion of inflammatory activity. |
| Time to Patient-Reported Outcome Based on 2 Items (PRO2) Flare | Baseline up to Week 48 | PRO2 flare was defined as a PRO2 score worsening of at least 2 points and an absolute PRO2 score of at least 3, with stool frequency subscore ≥2, and rectal bleeding subscore ≥1. PRO2 included items of stool frequency and rectal bleeding. The range of each item score was 0 to 3 with higher scores indicating more severe disease. |
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Baseline, Week 48 | The IBDQ is disease-specific questionnaire used for an assessment of Health Related Quality of Life (HRQoL) in participants with the Inflammatory Bowel Disease (IBD). It comprised of 32 questions divided into four health subscales: bowel symptoms (10 questions); systemic symptoms, including sleep disorders and fatigue (5 questions); emotional function such as depression, aggression, and irritation (12 questions); and social function, meaning the ability to participate in social activities and to work (5 questions). The IBDQ total score was calculated as the sum of the responses (each ranging from 1 \[severe problem\] to 7 \[normal health\]) to all 32 questions. Total IBDQ score ranged from 32 to 224 with a higher score indicating a better HRQoL. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation | Baseline up to Week 48 | An adverse event (AE) was any untoward medical occurrence, new or worsening of any preexisting condition, in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with this treatment. A TEAE was defined as * An AE which had a start date equal to or after the date of the first administration of study drug in this study and no later than 30 days after last administration of study drug. * And was either a newly reported event, or a worsening of an existing event. Serious TEAE was defined as a TEAE that * Resulted in death and was life-threatening; * Required in-patient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly / birth defect; * Was medically significant. |
| Change From Baseline in Fecal Calprotectin (FCP) | Baseline, Week 4, Week 12, Week 24, Week 36, and Week 48 | Fecal calprotectin, a very stable biomarker, was a 36 kilodalton calcium and zinc binding protein of S-100 protein family which was neutrophil derived. It represents 60% of cytosolic proteins in neutrophils and was a measurement of neutrophil migration to the gastrointestinal tract. |
Countries
Belgium, Czechia, France, Germany, Hungary, Italy, Poland, South Africa, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants who were in clinical remission with filgotinib 200 milligrams (mg) once daily for at least 2 consecutive quarterly visits in the ongoing long-term extension (LTE) SELECTION-LTE study (GS-US-418-3899; NCT02914535) and who met the eligibility criteria, were rolled over and randomized to this study. Participants were enrolled at study sites in Poland, France, Germany, the United States, Belgium, Republic of Korea, Spain, and the United Kingdom.
Pre-assignment details
The clinical trial was originally designed with the primary endpoint to be assessed at Week 48 after which participants would have received unblinded treatment. Due to early termination of the study, none of the participants completed 48 weeks of treatment. All participants participated in blinded treatment period only and the study was unblinded globally after study completion.
Participants by arm
| Arm | Count |
|---|---|
| Filgotinib 200 mg Participants received filgotinib 200 mg and placebo to match filgotinib 100 mg once daily orally. | 11 |
| Filgotinib 100 mg Participants received filgotinib 100 mg and placebo to match filgotinib 200 mg once daily orally. | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study terminated by sponsor | 10 | 10 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Filgotinib 100 mg | Total | Filgotinib 200 mg |
|---|---|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 10.7 | 57.4 years STANDARD_DEVIATION 9.5 | 56.5 years STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 21 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 21 Participants | 10 Participants |
| Sex: Female, Male Female | 6 Participants | 14 Participants | 8 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 6 / 11 | 6 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Percentage of Participants in Corticosteroid-free Clinical Remission Based on Modified Mayo Clinical Score (mMCS)
The mMCS is a tool designed to measure disease activity for ulcerative colitis. The mMCS was calculated as the sum of the 3 subscores: stool frequency, rectal bleeding, and endoscopy. Each subscore was graded from 0 to 3 with higher scores indicating more severe disease activity. The total mMCS score ranged from 0 to 9 with higher scores indicating more severe disease activity. The mMCS remission was defined as a total score of score ≤2, with endoscopic subscore of ≤1, stool frequency subscore of ≤1, and a rectal bleeding subscore of 0. Corticosteroid-free mMCS remission was defined as being free of corticosteroids for at least 12 weeks.
Time frame: Week 48
Population: As the study was terminated prior to any participant reaching the primary analysis time point at Week 48, the data for this endpoint was not collected and analyzed.
Secondary
Change From Baseline in C-Reactive Protein (CRP)
CRP is an acute-phase protein which provides an objective criterion of inflammatory activity.
Time frame: Baseline, Week 4, Week 12, Week 24, Week 36, and Week 48
Population: Participants in the FAS with available data were analyzed. As the study was terminated prior to any participant reaching the Week 48 time point, the data for Week 48 time point was not collected and analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Filgotinib 200 mg | Change From Baseline in C-Reactive Protein (CRP) | Change at Week 4 | 0.166 milligrams per liter (mg/L) | Standard Deviation 0.533 |
| Filgotinib 200 mg | Change From Baseline in C-Reactive Protein (CRP) | Change at Week 12 | 0.532 milligrams per liter (mg/L) | Standard Deviation 1.128 |
| Filgotinib 200 mg | Change From Baseline in C-Reactive Protein (CRP) | Change at Week 24 | 0.156 milligrams per liter (mg/L) | Standard Deviation 0.128 |
| Filgotinib 200 mg | Change From Baseline in C-Reactive Protein (CRP) | Change at Week 36 | 0.367 milligrams per liter (mg/L) | Standard Deviation 0.192 |
| Filgotinib 100 mg | Change From Baseline in C-Reactive Protein (CRP) | Change at Week 36 | 1.443 milligrams per liter (mg/L) | Standard Deviation 0.525 |
| Filgotinib 100 mg | Change From Baseline in C-Reactive Protein (CRP) | Change at Week 4 | 1.713 milligrams per liter (mg/L) | Standard Deviation 4.423 |
| Filgotinib 100 mg | Change From Baseline in C-Reactive Protein (CRP) | Change at Week 24 | 16.002 milligrams per liter (mg/L) | Standard Deviation 34.093 |
| Filgotinib 100 mg | Change From Baseline in C-Reactive Protein (CRP) | Change at Week 12 | 10.406 milligrams per liter (mg/L) | Standard Deviation 26.944 |
Secondary
Change From Baseline in Fecal Calprotectin (FCP)
Fecal calprotectin, a very stable biomarker, was a 36 kilodalton calcium and zinc binding protein of S-100 protein family which was neutrophil derived. It represents 60% of cytosolic proteins in neutrophils and was a measurement of neutrophil migration to the gastrointestinal tract.
Time frame: Baseline, Week 4, Week 12, Week 24, Week 36, and Week 48
Population: Participants in the FAS with available data were analyzed. As the study was terminated prior to any participant reaching the Week 48 time point, the data for Week 48 time point was not collected and analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Filgotinib 200 mg | Change From Baseline in Fecal Calprotectin (FCP) | Change at Week 4 | -27.6 milligrams per kilogram (mg/kg) | Standard Deviation 37.2 |
| Filgotinib 200 mg | Change From Baseline in Fecal Calprotectin (FCP) | Change at Week 12 | -16.7 milligrams per kilogram (mg/kg) | Standard Deviation 48.1 |
| Filgotinib 200 mg | Change From Baseline in Fecal Calprotectin (FCP) | Change at Week 24 | -52.0 milligrams per kilogram (mg/kg) | Standard Deviation 54.6 |
| Filgotinib 200 mg | Change From Baseline in Fecal Calprotectin (FCP) | Change at Week 36 | -46.5 milligrams per kilogram (mg/kg) | Standard Deviation 65.8 |
| Filgotinib 100 mg | Change From Baseline in Fecal Calprotectin (FCP) | Change at Week 36 | -8.0 milligrams per kilogram (mg/kg) | Standard Deviation 70.4 |
| Filgotinib 100 mg | Change From Baseline in Fecal Calprotectin (FCP) | Change at Week 4 | 142.5 milligrams per kilogram (mg/kg) | Standard Deviation 307.7 |
| Filgotinib 100 mg | Change From Baseline in Fecal Calprotectin (FCP) | Change at Week 24 | 374.3 milligrams per kilogram (mg/kg) | Standard Deviation 674.8 |
| Filgotinib 100 mg | Change From Baseline in Fecal Calprotectin (FCP) | Change at Week 12 | 920.6 milligrams per kilogram (mg/kg) | Standard Deviation 1996.2 |
Secondary
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score
The IBDQ is disease-specific questionnaire used for an assessment of Health Related Quality of Life (HRQoL) in participants with the Inflammatory Bowel Disease (IBD). It comprised of 32 questions divided into four health subscales: bowel symptoms (10 questions); systemic symptoms, including sleep disorders and fatigue (5 questions); emotional function such as depression, aggression, and irritation (12 questions); and social function, meaning the ability to participate in social activities and to work (5 questions). The IBDQ total score was calculated as the sum of the responses (each ranging from 1 \[severe problem\] to 7 \[normal health\]) to all 32 questions. Total IBDQ score ranged from 32 to 224 with a higher score indicating a better HRQoL.
Time frame: Baseline, Week 48
Population: As the study was terminated prior to any participant reaching the Week 48 time point, the data for this endpoint was not collected and analyzed.
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation
An adverse event (AE) was any untoward medical occurrence, new or worsening of any preexisting condition, in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with this treatment. A TEAE was defined as * An AE which had a start date equal to or after the date of the first administration of study drug in this study and no later than 30 days after last administration of study drug. * And was either a newly reported event, or a worsening of an existing event. Serious TEAE was defined as a TEAE that * Resulted in death and was life-threatening; * Required in-patient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly / birth defect; * Was medically significant.
Time frame: Baseline up to Week 48
Population: Participants in the Safety analysis set were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Filgotinib 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation | TEAEs | 6 Participants |
| Filgotinib 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation | Serious TEAEs | 0 Participants |
| Filgotinib 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation | TEAEs Leading to Treatment Discontinuation | 0 Participants |
| Filgotinib 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation | TEAEs | 6 Participants |
| Filgotinib 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation | Serious TEAEs | 0 Participants |
| Filgotinib 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation | TEAEs Leading to Treatment Discontinuation | 0 Participants |
Secondary
Time to ES-Confirmed UC Flare
An ES-confirmed UC flare was defined as an increase in rectal bleeding subscore by at least 1 point and an increase in stool frequency subscore by at least 2 points and an increase in endoscopic subscore by at least 1 point. Each subscore graded from 0 to 3 with higher scores indicating more severe disease.
Time frame: Baseline up to Week 48
Population: Participants in the FAS were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib 200 mg | Time to ES-Confirmed UC Flare | NA days |
| Filgotinib 100 mg | Time to ES-Confirmed UC Flare | NA days |
Secondary
Time to Patient-Reported Outcome Based on 2 Items (PRO2) Flare
PRO2 flare was defined as a PRO2 score worsening of at least 2 points and an absolute PRO2 score of at least 3, with stool frequency subscore ≥2, and rectal bleeding subscore ≥1. PRO2 included items of stool frequency and rectal bleeding. The range of each item score was 0 to 3 with higher scores indicating more severe disease.
Time frame: Baseline up to Week 48
Population: Participants in the Full Analysis Set (FAS) (all randomized participants who were administered study drug at least once) were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib 200 mg | Time to Patient-Reported Outcome Based on 2 Items (PRO2) Flare | NA days |
| Filgotinib 100 mg | Time to Patient-Reported Outcome Based on 2 Items (PRO2) Flare | NA days |