A Study Evaluating the Effect of Filgotinib Dose De-escalation in Participants With Ulcerative Colitis (UC) in Remission

Study Overview
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Brief Summary
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Participants who are in clinical remission on 200 mg filgotinib once daily (q.d.) for at least 2 consecutive quarterly visits in the ongoing SELECTION-LTE study (GS-US-418-3899, NCT02914535), are planned to be rolled over and randomized in this study. The primary objective of this study is to evaluate the efficacy of filgotinib in participants in stable clinical remission on 200 mg filgotinib q.d. for whom the dose was decreased to 100 mg q.d. compared to participants remaining on 200 mg q.d.

Official Title
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A Randomized, Double-blind, Controlled, Multi-center Study to Evaluate the Efficacy and Safety of Dose De-escalation of Orally Administered Filgotinib in Subjects With Ulcerative Colitis in Clinical Remission

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Filgotinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants must be participating in the SELECTION-LTE study (GS-US-418-3899), currently on 200 mg filgotinib q.d. and fulfill 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; FCP ≤250 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 a negative highly sensitive (serum beta human chorionic gonadotropin) pregnancy test during screening and must agree to continued monthly urine dipstick pregnancy testing during filgotinib treatment. Female participants of childbearing potential must agree 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 has a known hypersensitivity to filgotinib ingredients or history of a significant allergic reaction to filgotinib ingredients as determined by the investigator. Female participant who is pregnant or breastfeeding, or intending 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 is unable or unwilling to comply with restrictions regarding prior and concomitant medication as described in the protocol. Participant has a positive QuantiFERON® tuberculosis (TB) test at screening or has 2 indeterminate QuantiFERON® TB test results that require IP treatment interruption, or participant has 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 have been successfully treated for nonmelanoma skin cancer or cervical carcinoma in situ. Participant meets discontinuation criteria of the SELECTION-LTE study (GS-US-418-3899). NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Filgotinib 200 mg<br>Participants will receive filgotinib 200 mg and placebo to match filgotinib 100 mg. Participants will receive blinded treatment until primary analysis time point (after last participant completes Week 48 post baseline visit or has completed Week 12 post re-escalation visit, or after last follow-up of participant who discontinues prior to Week 48, whichever comes last), with exception of participants with endoscopic score (ES)-confirmed UC flare who will be switched to open-label 200 mg filgotinib q.d. for at least 12 weeks and may continue treatment in case of response until the end of the study. Participants, who are blinded at the time of the primary analysis time point, will receive open-label filgotinib 200 mg q.d. The maximum duration of the treatment will be 216 weeks. | Drug: Filgotinib<br>* Tablets administered orally once daily<br>* Other names: GLPG0634;Drug: Placebo<br>* Tablets administered orally once daily<br>|
| Experimental: Filgotinib 100 mg<br>Participants will receive filgotinib 100 mg and placebo to match filgotinib 200 mg. Participants will receive blinded treatment until primary analysis time point (after last participant completes Week 48 post baseline visit or has completed Week 12 post re-escalation visit, or after last follow-up of participant who discontinues prior to Week 48, whichever comes last), with exception of participants with ES-confirmed UC flare who will be switched to open-label 200 mg filgotinib q.d. for at least 12 weeks and may continue treatment in case of response until the end of the study. Participants, who are blinded at the time of the primary analysis time point, will receive open-label filgotinib 100 mg q.d. The maximum duration of the treatment will be 216 weeks. | Drug: Filgotinib<br>* Tablets administered orally once daily<br>* Other names: GLPG0634;Drug: Placebo<br>* Tablets administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Corticosteroid-free Clinical Remission Based on Modified Mayo Clinical Score (mMCS) at Week 48 | mMCS score is composed of subscores from rectal bleeding, stool frequency, and endoscopic findings (the range of each subscore is 0 to 3 with higher score indicating severe disease). mMCS remission is defined as mMCS score ≤2, with endoscopic subscore of ≤1, stool frequency subscore of ≤1, and a rectal bleeding subscore of 0. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Patient-Reported Outcome Based on 2 Items (PRO2) Flare | PRO2 includes items of stool frequency and rectal bleeding. The range of each item score is 0 to 3 with higher score indicating severe disease. PRO2 flare is 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. | Baseline (Day 1) up to 216 weeks | 
| Time to ES-Confirmed UC Flare | An ES-confirmed UC flare is 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. The range of each item score is 0 to 3 with higher score indicating severe disease. | Baseline (Day 1) up to 216 weeks | 
| Change From Baseline in C-Reactive Protein (CRP) up to Week 48 |  | Baseline, up to Week 48 | 
| Change From Baseline in Fecal Calprotectin (FCP) up to Week 48 |  | Baseline, up to Week 48 | 
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 48 | IBDQ consists of 32 questions divided into four dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). Every question has graded responses from 1 (worst situation) to 7 (best situation). The total score is the sum of the score from each question and ranges from 32 to 224 with higher scores representing better quality of life. | Baseline, Week 48 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events, and TEAEs Leading to Treatment Discontinuation |  | Baseline up to 216 weeks |