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Filgotinib

Phase 3

Crohn's Disease | Small molecule | Immunology |Galapagos NV|Last Updated: Jun 4, 2024

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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment1,372
FDA Designations
No designations recorded
Clinical trial landscape

Filgotinib · 6 trials · 6 indications

Phase 3 1Phase 2 4Phase 1 1
NCT02914561Filgotinib in the Induction and Maintenance of Remission in Adults With Moderately to Severely Active Crohn's DiseaseCrohn's Disease
COMPLETED1,372 Analytics
PHASE3COMPLETED
Filgotinib in the Induction and Maintenance of Remission in Adults With Moderately to Severely Active Crohn's Disease
Crohn's DiseaseUnlock trial analytics
Study Endpoints
Primary Endpoints
Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10
Week 10

The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI of \< 150 points.

Induction Study: Percentage of Participants Who Achieved Endoscopic Response at Week 10
Week 10

The Simple Endoscopic Score for Crohn's Disease (SES-CD) assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Endoscopic response was defined as ≥ 50% reduction from baseline in total SES-CD score.

Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by CDAI at Week 58
Week 58

The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The sub scores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI of \< 150 points.

Maintenance Study: Percentage of Participants Who Achieved Endoscopic Response at Week 58
Week 58

The SES-CD assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Endoscopic response was defined as ≥ 50% reduction from baseline in total SES-CD score.

Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13
Baseline to Week 13

Baseline for sperm/semen parameters was the mean of 2 evaluable semen samples at screening. The normal range for sperm concentration is ≥15 million sperms/mL. Percentage change = (\[mean at Week 13 - baseline\] / baseline) × 100; value at Week 13 was the mean of 2 evaluable samples collected at Week 13.

Percentage of subjects who have reached ACR20 response as compared to placebo
Week 16

To assess the effect of filogotinib on PsA as assessed by ACR20 in PsA patients

Ankylosing Spondylitis disease activity score (ASDAS) in filgotinib treated subjects as compared to placebo
week 12

To evaluate the effect of filgotinib on the AS disease activity score

Number of Participants Experiencing Treatment-Emergent Adverse Events
From First dose to Week 437

An Adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. Treatment-emergent adverse events (TEAEs) were defined as any AEs with an onset date on or after the filgotinib start date in the core studies or GLPG0634-CL-205 (NCT02065700), and no later than 30 days after permanent discontinuation of filgotinib in GLPG0634-CL-205 (NCT02065700) or of either 30 days after the last dose date.

Maximum observed plasma concentration of filgotinib (Cmax)
From Day 1 pre-dose until Day 15
Cmax of GS-829845, major active metabolite
From Day 1 pre-dose until Day 15
Area under the plasma concentration-time curve from time zero till the last observed quantifiable concentration of filgotinib (AUC0-t)
From Day 1 pre-dose until Day 15
AUC0-t of GS-829845, major active metabolite
From Day 1 pre-dose until Day 15
Area under the plasma concentration time curve from time zero to infinity of filgotinib (AUC0-inf)
From Day 1 pre-dose until Day 15
AUC0-inf of GS-829845, major active metabolite
From Day 1 pre-dose until Day 15
Secondary Endpoints
Induction Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 10
Week 10
Induction Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 10
Week 10
Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 58
Week 58
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Cohort A: Filgotinib 200 (mg) (Induction Study)EXPERIMENTALBiologic naïve and biologic experienced participants received filgotinib 200 milligram (mg) with placebo-to-match (PTM) filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
Cohort A: Filgotinib 100 mg (Induction Study)EXPERIMENTALBiologic naïve and biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.
Cohort A: Placebo (Induction Study)PLACEBO_COMPARATORBiologic naïve and biologic experienced participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
Cohort B: Filgotinib 200 mg (Induction Study)EXPERIMENTALBiologic experienced participants received filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
Cohort B: Filgotinib 100 mg (Induction Study)EXPERIMENTALBiologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.
Cohort B: Placebo (Induction Study)PLACEBO_COMPARATORBiologic experienced participants received PTM filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)EXPERIMENTALParticipants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.
Filgotinib 200 mg to Placebo (Maintenance Study)EXPERIMENTALParticipants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.
Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)EXPERIMENTALParticipants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.
Filgotinib 100 mg to Placebo (Maintenance Study)EXPERIMENTALParticipants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.
Placebo to Placebo (Maintenance Study)PLACEBO_COMPARATORParticipants who received placebo in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.
FilgotinibEXPERIMENTALParticipants received filgotinib 200 milligrams (mg) tablet, orally, once daily up to Week 13 in the double-blind (DB) phase. At Week 13, participants who were arthritis responders, were unblinded and received open-label (OL) treatment filgotinib 200 mg, tablet, orally, once daily up to approximately 143 weeks (until Week 156) in the extension (EXT) phase and participants who were arthritis nonresponders discontinued blinded study drug and started standard of care (SOC) treatment in the EXT phase. Participants on DB treatment or OL filgotinib who entered the monitoring phase (if their sperm parameters met ≥50% decrease threshold in pre-specified semen parameters) discontinued the study drug and started SOC for up to 52 weeks.
PlaceboPLACEBO_COMPARATORParticipants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase. At Week 13, participants were unblinded and started SOC treatment in the EXT phase for up to approximately 143 weeks (until Week 156). Participants who entered the monitoring phase (if their sperm parameters met ≥50% decrease threshold in pre-specified semen parameters) continued on SOC treatment.
oral filgotinib tabletsEXPERIMENTAL -
placebo tabletsPLACEBO_COMPARATOR -
Filgotinib Darwin 1EXPERIMENTALParticipants in Study GLPG0634-CL-203 (NCT01888874) were rolled-over to receive an oral dose of filgotinib at a daily dose of 200 milligrams (mg) in this extension study, with the exception of male participants in the United States (US) who were limited to a daily dose of 100 mg due to a Food and Drug Administration (FDA) requirement based on a non-clinical finding. Treatment was administered until marketing, local (if applicable) regulatory and/or pertinent local reimbursement approval. In case of intolerance or for safety reasons, and as per investigator's discretion, a daily dose of filgotinib 200 mg could be decreased to 100 mg per day, and later returned to 200 mg per day after the reasons for decreasing the dose were resolved.
Filgotinib Darwin 2EXPERIMENTALParticipants from Study GLPG0634-CL-204 (NCT01894516) were rolled-over to receive oral dose of filgotinib tablet at 200 mg once daily (q.d) in this extension study. Treatment was administered until marketing, local (if applicable) regulatory and/or pertinent local reimbursement approval. Participants started the study with the same dose level (filgotinib 200 mg per day) and in case of intolerance or safety reasons and as per investigator's discretion, the daily dose of filgotinib was decreased to 100 mg q.d and was returned to 200 mg per day after the reasons for decreasing the dose had resolved and at the investigator's discretion.
Treatment A:ACTIVE_COMPARATORfilgotinib administered under fasting conditions
Treatment B:EXPERIMENTALfilgotinib administered under fasting conditions
Treatment C:EXPERIMENTALfilgotinib administered under high-fat fed conditions
Interventions
NameTypeDescription
FilgotinibDRUGFilgotinib tablets administered orally once daily.
PlaceboOTHERPlacebo administered orally once daily.
Standard of CareDRUGLocally approved treatment, accepted by medical experts as a proper treatment for rheumatic conditions, prescribed according to best clinical practice, with no known testicular toxicity.
Placebo Oral TabletDRUGone placebo oral tablet q.d.
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Eligibility Criteria
Age Range18 Years to 75 Years
SexALL
Healthy VolunteersNo
Study Sites513

Key Inclusion Criteria: * Documented diagnosis of CD with a minimum disease duration of 3 months with involvement of the ileum and/or colon at a minimum, as determined by histopathology and endoscopic assessment * Moderately to severely active CD * Cohort A (Biologic Naïve): Previously demonstrated...

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