Clinical Trials Register

Summary
EudraCT Number:	2012-005521-73
Sponsor's Protocol Code Number:	GLPG0974-CL-201
National Competent Authority:	Latvia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-03-13
Trial results	Removed from public view

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Latvia - SAM

A.2

EudraCT number

2012-005521-73

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Placebo-controlled, proof-of-concept oral dose study to explore the safety, pharmacokinetics and pharmacodynamics in subjects with mild to moderate ulcerative colitis

A.3.2

Name or abbreviated title of the trial where available

Proof-of-concept oral dose, safety, tolerability, efficacy, PK and PD study

A.4.1

Sponsor's protocol code number

GLPG0974-CL-201

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Galapagos NV
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Galapagos NV
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Galapagos NV
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Generaal De Wittelaan L11 A3
B.5.3.2	Town/ city	Mechelen
B.5.3.3	Post code	2800
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+3225342 900
B.5.5	Fax number	+3215342 901
B.5.6	E-mail	rd@glpg.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	GLPG0974
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GLPG0974
D.3.9.2	Current sponsor code	G279874
D.3.9.4	EV Substance Code	SUB33026
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Mild to moderate Ulcerative Colitis

E.1.1.1

Medical condition in easily understood language

inflammatory conditions of the intestinal tract

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10009900
E.1.2	Term	Colitis ulcerative
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the safety and tolerability of GLPG0974 given to UC subjects for 28 days compared to placebo.

E.2.2

Secondary objectives of the trial

1.To explore the efficacy of GLPG0974 versus placebo in mild to moderate Ulcerative Colitis (UC) by use of efficacy measures such as the Mayo score, Partial Mayo Score and histopathological Geboes index
2.To characterize the PK of GLPG0974 in UC subjects.
3.To explore the effects of GLPG0974 on selected biomarkers (e.g. faecal calprotectin, MPO in biopsy and serum CRP) and on microbiota.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Men or women between 18 to 75 years of age inclusive, on the day of signing the informed consent.
2.Documented history of UC (at least 6 months prior to randomization) with histological confirmation of diagnosis.
3.Presence of mild-to-moderately active ulcerative colitis for a minimum period of 14 days and spread beyond the rectum (inflammation extending ≥15 cm from anal verge) as evidenced by clinical signs and endoscopy.
4.Medication: 5-ASA for at least 12 weeks and stable dose for > 4 weeks or discontinued for> 4 weeks prior to randomization. Rectal medications stopped for > 2 weeks prior to randomization.
5.Baseline Mayo score 4-10 (inclusive) with rectal bleeding sub-score of ≥ 1, endoscopy score ≥ 1 and Physician’s rating of disease activity < 3.
6.Absence of infectious colitis as evidenced by negative stool culture for enteric pathogens, negative Clostridium difficile cytotoxin assay, and negative microscopic stool examination for intestinal parasites.
7.Women must have a negative pregnancy test unless they are surgically sterile or have been post-menopausal for at least one year (12 consecutive months without menses); in case of doubt a determination of serum follicle stimulating hormone (FSH) can be done with FSH levels above 35 mIU/mL being confirmative for menopause.
8.Women of childbearing potential must use a medically acceptable form of birth control and agree to continue its use during the study and for at least twelve weeks after the last dose of study drug. Women who have had a complete surgical hysterectomy or are postmenopausal are exempt from this requirement. Medically acceptable forms of birth control include oral contraceptives, injectable or implantable methods, intrauterine devices, tubal ligation (if performed more than one year before screening), or double barrier contraception. Sexually active men must agree to use a medically acceptable form of contraception (double barrier) during the study and continue its use for at least twelve weeks after the last dose of study drug.
9.Able and willing to give voluntary written informed consent and agree to schedule of assessments.

E.4

Principal exclusion criteria

1.History of sensitivity to any component of the study drug, or a history of drug or other allergy that, in the Investigator’s opinion, contraindicates subject’s participation in the study.
2.Any concurrent illness, condition, disability or clinically significant abnormality (including laboratory tests) that, in the Investigator’s opinion, represents a safety risk for subject’s participation in the study, may affect the interpretation of clinical safety or efficacy data, or may prevent the subject to safely complete the assessments required by the protocol, including:
a.Hemoglobin <8.5 g/dL
b.White blood cells (WBC) count <3.0 x 109 cells/L
c.Neutrophil count <1.5 x 109 cells/L
d.Platelet count <100 x109 cells/L
e.Serum ALT >1.5 x upper limit of normal (ULN)
f.HbA1c > 6%
g.Total bilirubin level >1.25 x ULN
h.Creatinine clearance <80 mL/min using the Cockroft-Gault formula
3.Positive serology for human immunodeficiency virus (HIV)1 or 2 or hepatitis B or C, or any history of HIV or hepatitis from any cause with the exception of hepatitis A.
4.History of active infections requiring intravenous antibiotics within the past four weeks prior to randomization.
5.History of malignancy within the past five years (except for basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been treated with no evidence of recurrence).
6.History of bowel surgery within 12 months prior to screening, or presence or history of intestinal malignancy (if any unexpected lesion is observed during screening endoscopy, additional biopsies should be taken for histopathological assessment in the local lab to and recruitment into the study must be deferred until the results are available).
7.Suspicion of Crohn’s disease, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis, based on medical history, endoscopy and/or histological findings. For subjects with a documented history of UC of ≥ 8 years a total colonoscopy should have been done within the 2 years prior to screening or performed at Day 1 prior to randomization. to exclude the aforementioned conditions.
8.History of lower GI bleeding disorder, other than UC.
9.A history of significant psychological, neurologic, hepatic, renal, endocrine, cardiovascular, gastrointestinal (other than UC), pulmonary or metabolic disease.
10.History of tuberculosis (TB) infection as determined by:
a.positive diagnostic TB test result (defined as a positive QuantiFERON
TB Gold test),
OR
b.a chest radiograph (both posterior-anterior and lateral views), taken within
three months prior to screening and read by a qualified radiologist, with
evidence of current active TB or old inactive TB.
i.e. both tests must be negative for thesubject to be eligible.
11.Treatment with systemic corticosteroids within 1 week prior to randomization.
12.If topical corticosteroids are being used for other chronic inflammatory conditions, the subject may be included at the discretion of the Investigator after discussion with the medical monitor.
13.Treatment with TNF-α inhibitors or other biologics within 2 months prior to randomization.
14.Treatment with immunosuppressants (azathioprine or 6-mercaptopurine or methotrexate), if initiated within 3 months prior to randomization, or if changed in terms of drug or dose within 3 months prior to randomization .
15.Current use of probiotic or prebiotic preparations
16.Regular daily use of non-steroidal anti-inflammatory drugs (NSAIDs), except low dose aspirin (100 mg/day) for cardioprotection, within 7 days prior to randomization.
17.Administration of any experimental therapy within 90 days or 5 times the half-life of the experimental therapy whichever is longer prior to screening..
18.History within the previous two years or current evidence of drug or alcohol abuse.
19.Pregnant or lactating women.
20.Medical, psychiatric, cognitive, or other conditions that, according to investigator’s medical judgment, compromise the subject's ability to understand the subject information, to give informed consent, to comply with the requirements of the study protocol (that is likely to affect the subject’s return for visits on schedule), or ability to complete the study.

E.5 End points

E.5.1

Primary end point(s)

Safety Endpoints:
- Frequency of Serious adverse events in GLPG0974 versus placebo group.
- Frequency of Adverse events in GLPG0974 versus placebo group.
- Changes in physical examinations, vital signs, 12-lead ECG and laboratory parameters over the duration of the study in GLPG0974 versus placebo group.

E.5.1.1

Timepoint(s) of evaluation of this end point

At different timepoints from signing informed consent until follow-up visit : (S)AE, laboratory parameters
Scr., D1, D8, D29 and D43: ECG and Vital signs
Scr., D1, D29 and D43: Physical exam

E.5.2

Secondary end point(s)

Efficacy Endpoints:
- Mayo score
- Partial Mayo Score
- Geboes Index

PK parameters:
- GLPG0974 in blood
PD parameters:
- fecal calprotectin analysis on stool samples
- MPO measurement on biopsy samples
- serum CRP analysis
- microbiota analysis on stool and biopsy samples

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy Endpoints:
- Mayo score: D1 and D29
- Partial Mayo score: D8 and D15
- Geboes Index: D1 and D29

PK parameters: D8, D15 and D29

PD parameters:
- fecal calprotectin analysis on stool samples: D1, D8, D15 and D29
- MPO measurement on biopsy samples: D1 and D29
- serum CRP analysis: Scr., D1, D8, D15, D29 and D43
- microbiota analysis on stool and biopsy samples D1 and D29

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Exploratory, proof-of-concept

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

last contact with the last subject in the study

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception