Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Study of GLPG0974 in Subjects With Ulcerative Colitis

Study Overview
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Brief Summary
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Approximately 45 patients suffering from mild to moderate ulcerative colitis will be examined for any side effects (safety and tolerability) that may occur when taking GLPG0974 or matching placebo (2:1 ratio) for 28 days. During the course of the study, patients will also be evaluated for improvement of disease activity by different efficacy measures, the amount of GLPG0974 present in the blood determined (PK) and the effects of GLPG0974 on selected biomarkers (PD) in the blood, colon biopsies and faeces will be explored.

Official Title
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Exploratory, Phase II, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of GLPG0974 in Subjects With Mild to Moderate Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: GLPG0974
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Men or women between 18 to 75 years of age inclusive, on the day of signing the informed consent with a documented history of UC. Presence of mild-to-moderately active ulcerative colitis as evidenced by clinical signs and endoscopy. Medication: 5-ASA. Absence of infectious colitis. Key Exclusion Criteria: History of sensitivity to any component of the study drug Any concurrent illness, condition, disability or clinically significant abnormality (including lab tests) that represents a safety risk , may affect the interpretation of data, or may prevent the subject to safely complete the assessments Positive serology for HIV 1 or 2 or hepatitis B or C, or any history of HIV or hepatitis. History of active infections requiring intravenous antibiotics within the past four weeks prior to randomization. History of bowel surgery, or presence or history of intestinal malignancy. Suspicion of Crohn's disease, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis. History of lower GI bleeding disorder, other than UC. A history of significant psychological, neurologic, hepatic, renal, endocrine, cardiovascular, gastrointestinal (other than UC), pulmonary or metabolic disease. History of tuberculosis (TB) infection. Treatment with systemic corticosteroids within 1 week prior to randomization. Treatment with TNF-α inhibitors or other biologics within 2 months prior to randomization. Treatment with immunosuppressants, initiated or changed within 3 months prior to randomization . Current use of probiotic or prebiotic preparations Regular daily use of NSAIDs, within 7 days prior to randomization. Administration of any experimental therapy within 90 days or 5x the half-life. History of drug or alcohol abuse. Pregnant or lactating women. Medical, psychiatric, cognitive, or other conditions that compromise the subject's ability to complete the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: GLPG0974<br>1 capsule of 200 mg GLPG0974 twice daily | Drug: GLPG0974<br>* 1 capsule in the morning and 1 capsule in the evening with food during 28 days<br>|
| Placebo Comparator: Placebo<br>1 capsule placebo twice daily | Drug: Placebo<br>* 1 capsule in the morning and 1 capsule in the evening with food during 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | To evaluate the safety and tolerability of GLPG0974 in terms of the number of adverse events reported | Screening up to Follow up (14 days after last dosing) | 
| Changes in physical exam measures | To evaluate the safety and tolerability of GLPG0974 in terms of the changes in physical exam measures reported | Screening up to Follow up (14 days after last dosing) | 
| Changes in vital signs as measured by heart rate, blood pressure and oral temperature | To evaluate the safety and tolerability of GLPG0974 in terms of the changes in vital signs as measured by heart rate, blood pressure and oral temperature reported | Screening up to Follow up (14 days after last dosing) | 
| Changes in 12-lead ECG measures | To evaluate the safety and tolerability of GLPG0974 in terms of the changes in 12-lead ECG measures reported | Screening up to Follow up (14 days after last dosing) | 
| Changes in blood safety lab parameters | To evaluate the safety and tolerability of GLPG0974 in terms of changes in blood safety lab parameters reported | Screening up to Follow up (14 days after last dosing) | 
| Changes in urine safety lab parameters | To evaluate the safety and tolerability of GLPG0974 in terms of changes in urine safety lab parameters reported | Screening up to Follow up (14 days after last dosing) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in (partial) Mayo clinical disease activity score | To evaluate the efficacy of GLPG0974 in terms of changes in (partial) Mayo clinical disease activity score reported | From Day 1 to Day 29 | 
| Changes in histopathological clinical activity score in colon biopsies | To evaluate the efficacy of GLPG0974 in terms of changes in histopathological clinical activity score (Geboes score) in colon biopsies reported | Day 1 and Day 29 | 
| The amount of GLPG0974 in plasma over time after multiple oral doses of GLPG0974 | To evaluate the amount of GLPG0974 in plasma over time after multiple oral doses of GLPG0974 - pharmacokinetics (PK) in ulcerative colitis patients | Day 8, Day 15 and Day 29 | 
| Changes in the levels of faecal calprotectin over time after multiple oral doses of GLPG0974 | To evaluate the changes in the levels of calprotectin in faeces over time after multiple oral doses of GLPG0974 - pharmacodynamics (PD) in ulcerative colitis patients | Screening up to Day 29 | 
| Changes in the levels of C-reactive protein in serum over time after multiple oral doses of GLPG0974 | To evaluate the changes in the levels of C-reactive protein in serum over time after multiple oral doses of GLPG0974 - pharmacodynamics (PD) in ulcerative colitis patients | Screening up to Day 29 | 
| Changes in the levels of myeloperoxidase (MPO) in colon biopsies over time after multiple oral doses of GLPG0974 | To evaluate the changes in the levels of MPO in colon biopsies over time after multiple oral doses of GLPG0974 - pharmacodynamics (PD) in ulcerative colitis patients | Day 1 and Day 29 | 
| Changes in the levels of predominant microbiota in faeces over time after multiple oral doses of GLPG0974 | To evaluate the changes in the levels of predominant microbiota in faeces over time after multiple oral doses of GLPG0974 - pharmacodynamics (PD) in ulcerative colitis patients | Day 1 and Day 29 | 
| Changes in the levels of predominant microbiota in colon biopsies over time after multiple oral doses of GLPG0974 | To evaluate the changes in the levels of predominant microbiota in colon biopsies over time after multiple oral doses of GLPG0974 - pharmacodynamics (PD) in ulcerative colitis patients | Day 1 and Day 29 |