Efficacy and Safety of GLPG1205 in Subjects With Active Ulcerative Colitis

Study Overview
=================
Brief Summary
-----------------
Approximately 60 patients suffering from moderate to severe ulcerative colitis will be evaluated for improvement of disease activity (efficacy) when taking GLPG1205 or matching placebo once daily for 12 weeks in addition to their stable background treatment. During the course of the study, patients will also be examined for any side effects that may occur (safety and tolerability), and the amount of GLPG1205 present in the blood (Pharmacokinetics) as well as the effects of GLPG1205 on disease- and mechanism of action-related parameters (Pharmacodynamics) in blood, stool and colonic biopsies will be determined.

Official Title
-----------------
Phase II, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of GLPG1205 in Patients With Moderate to Severe Ulcerative Colitis

Conditions
-----------------
Ulcerative Colitis

Intervention / Treatment
-----------------
* Drug: GLPG1205
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects between 18 and 75 years Documented history of UC Presence of active UC for a minimum period of 14 days prior to screening and spread beyond the rectum, Mayo score ≥ 6 with rectal bleeding score ≥ 1 and endoscopy score ≥ 2 Absence of infectious colitis Tumor necrosis factor alpha (TNFα) inhibitor-naive subjects should have failed at least 1 prior conventional therapy Continuation of concurrent treatment with oral steroids (≤30 mg prednisolone eq/day), immunosuppressants and 5-aminosalicylates at stable dose is allowed Female subjects must have a negative blood pregnancy test, unless they are surgically sterile, had a hysterectomy, or have been postmenopausal for at least 1 year Subjects will have to use highly effective contraceptive methods Exclusion Criteria: History of sensitivity to any component of the study drug, or a history of drug or other allergy Any concurrent illness, condition, disability, or clinically significant abnormality that, in the investigator's opinion, represents a safety risk for the subject's participation, may affect the interpretation of data, or may prevent the subject from safely completing the assessments History of significant psychological, neurologic, hepatic, renal, endocrine, cardiovascular, GI (other than UC), pulmonary, or metabolic disease History of active infections requiring intravenous antibiotics within the past 4 weeks prior to screening. History of malignancy within the past 5 years; presence or history of intestinal malignancy History of bowel surgery within 6 months prior to screening; history of colon resection with < 30 cm of the colon remaining Suspicion of Crohn's disease, indeterminate colitis, microscopic colitis, ischemic colitis, diverticular disease-associated colitis, or radiation-induced colitis Subject who has received non-permitted UC therapies within specified timeframes, depending on the medication, as stated in the protocol Subject who is pregnant or lactating

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLPG1205 100mg QD<br>GLPG1205 100mg daily dosing in the morning | Drug: GLPG1205<br>* GLPG1205 daily dosing in the morning for 12 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo daily dosing in the morning | Drug: Placebo<br>* placebo daily dosing in the morning daily for 12 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Mayo score at Week 8 | To evaluate the efficacy of GLPG1205 in terms of changes in Mayo score comparing results at Week 8 with baseline between GLPG1205 treated subjects and placebo subjects | Screening and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in partial Mayo score | To evaluate the efficacy of GLPG1205 in terms of changes in partial Mayo score comparing results with baseline between GLPG1205 treated subjects and placebo subjects at every visit up to Week 12 | From Screening to Week 12 | 
| Histological response rate | To evaluate the efficacy of GLPG1205 in terms of histological response rate by use of the histopathological Geboes index comparing results at Week 8 with baseline between GLPG1205 treated subjects and placebo subjects | Screening and Week 8 | 
| Number of subjects with adverse events | To evaluate the safety and tolerability of GLPG1205 between GLPG1205 treated subjects and placebo subjects in terms of adverse events at every visit | From Screening to Week 16 | 
| Number of subjects with abnormal laboratory parameters | To evaluate the safety and tolerability of GLPG1205 between GLPG1205 treated subjects and placebo subjects in terms of abnormal laboratory parameters at every visit | From Screening to Week 16 | 
| Number of subjects with abnormal vital signs | To evaluate the safety and tolerability of GLPG1205 between GLPG1205 treated subjects and placebo subjects in terms of abnormal vital signs at every visit | From Screening to Week 16 | 
| Number of subjects with abnormal electrocardiogram | To evaluate the safety and tolerability of GLPG1205 between GLPG1205 treated subjects and placebo subjects in terms of abnormal electrocardiograms at every visit | From Screening to Week 16 | 
| Number of subjects with abnormal physical examination | To evaluate the safety and tolerability of GLPG1205 between GLPG1205 treated subjects and placebo subjects in terms of abnormal physical examination at every visit | From Screening to Week 16 | 
| The plasma levels of GLPG1205 | To characterize the pharmacokinetics (PK) of GLPG1205 by measuring the amount in plasma at Week 4, 8 and 12 | Week 4, 8 and 12 | 
| Changes in serum C-reactive protein (CRP) levels | To characterize the pharmacodynamics (PD) of GLPG1205 by measuring the levels of C-reactive protein in serum at every visit | From Screening to Week 16 | 
| Changes in faecal calprotectin levels | To characterize the pharmacodynamics (PD) of GLPG1205 by measuring the levels of faecal calprotectin in stool at every visit up to Week 12 | From Screening to Week 12 | 
| Changes in myeloperoxidase (MPO) levels in colonic biopsies | To characterize the pharmacodynamics (PD) of GLPG1205 by measuring the levels of myeloperoxidase (MPO) in colonic biopsies at Screening and Week 8 | Screening and Week 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
moderate to severe ulcerative colitis, GLPG1205