Clinical trial NCT01829321: Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Study of GLPG0974 in Subjects With Ulcerative Colitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2013-04-11
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: * 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of adverse events
timeFrame: Screening up to Follow up (14 days after last dosing)
measure: Changes in physical exam measures
timeFrame: Screening up to Follow up (14 days after last dosing)
measure: Changes in vital signs as measured by heart rate, blood pressure and oral temperature
timeFrame: Screening up to Follow up (14 days after last dosing)
measure: Changes in 12-lead ECG measures
timeFrame: Screening up to Follow up (14 days after last dosing)
measure: Changes in blood safety lab parameters
timeFrame: Screening up to Follow up (14 days after last dosing)
measure: Changes in urine safety lab parameters
timeFrame: Screening up to Follow up (14 days after last dosing)
Secondary outcomes:
measure: Changes in (partial) Mayo clinical disease activity score
timeFrame: From Day 1 to Day 29
measure: Changes in histopathological clinical activity score in colon biopsies
timeFrame: Day 1 and Day 29
measure: The amount of GLPG0974 in plasma over time after multiple oral doses of GLPG0974
timeFrame: Day 8, Day 15 and Day 29
measure: Changes in the levels of faecal calprotectin over time after multiple oral doses of GLPG0974
timeFrame: Screening up to Day 29
measure: Changes in the levels of C-reactive protein in serum over time after multiple oral doses of GLPG0974
timeFrame: Screening up to Day 29
measure: Changes in the levels of myeloperoxidase (MPO) in colon biopsies over time after multiple oral doses of GLPG0974
timeFrame: Day 1 and Day 29
measure: Changes in the levels of predominant microbiota in faeces over time after multiple oral doses of GLPG0974
timeFrame: Day 1 and Day 29
measure: Changes in the levels of predominant microbiota in colon biopsies over time after multiple oral doses of GLPG0974
timeFrame: Day 1 and Day 29
Other outcomes:
Locations:
city: Bonheiden
country: Belgium
facility: Imelda
city: Gent
country: Belgium
facility: UZ Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Hradec Kralove
country: Czech Republic
facility: Hepato-Gastroenterologie HK, s.r.o.
city: Olomouc
country: Czech Republic
facility: Fakulní nemocnice Olomouc
city: Prague
country: Czech Republic
facility: Homolka Hospitál
city: Slany
country: Czech Republic
facility: Nemocnice Slaný
city: Usti nad Labem
country: Czech Republic
facility: Krajská zdravotní a.s., Masarykova nemocnice v Ústí nad Labem T. Bati a.s.
city: Zlin
country: Czech Republic
facility: Krajská nemocnice Tomáše Bati - Zlin
city: Znojmo
country: Czech Republic
facility: Nemocnice Znojmo
city: Riga
country: Latvia
facility: Latvijas Jūras Medicīnas Centrs
city: Riga
country: Latvia
facility: Rīgas slimnīca Bikor Holim
city: Riga
country: Latvia
facility: SIA Gremošanas slimību centrs "Gastro"
city: Bratislava
country: Slovakia
facility: Univerzitná nemocnica Bratislava
city: Nitra
country: Slovakia
facility: Fakultná Nemocnica Nitra
Study officials:
affiliation: Galapagos NV
name: Frédéric Vanhoutte, MD
role: STUDY_DIRECTOR
References: