Placebo-controlled study to assess efficicay, safety and tolerability and to investigate the pharmacokinetics of GLPG1205 in subjects with moderate Crohn's disease

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2014-001892-30-BE
• Date of registration: 18/09/2014
• Prospective Registration: Yes
• Primary sponsor: Galapagos NV
• Public title: Placebo-controlled study to assess efficicay, safety and tolerability and to investigate the pharmacokinetics of GLPG1205 in subjects with moderate Crohn's disease
• Scientific 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 Crohn’s Disease
• Date of first enrolment: 24/11/2014
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001892-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, Czech Republic, France, Germany, Hungary, Poland, Russian Federation, Spain, Ukraine, United Kingdom

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Galapagos NV

• Name: Clinical Trial Information Desk
• Affiliation: Galapagos NV

Key inclusion & exclusion criteria

Inclusion criteria:
1.Male or female between 18 and 75 years of age inclusive, on the day of signing the informed consent form.
2.Documented history of colonic or ileocolonic CD (at least 6 months prior to baseline) as assessed by colonoscopy and supported by histological assessment.
3.Crohn’s Disease Activity Index score during screening = 220 to = 450.
4.Evidence of active disease as demonstrated by a simplified endoscopic activity score (SES-CD) > 7 with Presence of Ulcers subscore = 1 in at least 1 segment (confirmed by the Core Imaging Laboratory).
5.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.
6.Allowed current CD treatment:
a.5-Aminosalicylates ([5-ASAs]; mesalazine, olsalazine, or sulfasalazine) for at least 12 weeks and at a stable dosage for > 4 weeks and will be maintained at this dosage throughout the study or discontinued for > 4 weeks prior to baseline
AND/OR
b.Immunosuppressants (azathioprine or 6-mercaptopurine) if initiated and at a stable dosage > 3 months prior to baseline and will be maintained at this dosage throughout the study
AND/OR
c.Oral steroids = 30 mg prednisolone equivalent/day or oral budesonide = 9 mg/day and has been stable for at least 2 weeks prior to baseline and will be maintained at this dosage throughout the study.
7.Tumor necrosis factor alpha (TNFa) inhibitor-naïve subjects should have failed at least 1 prior conventional therapy (e.g., ASAs, steroids, and/or immunomodulators).
8.Absence of current active or history of tuberculosis (TB) infection as determined by a negative QuantiFERON TB Gold test at screening.
9.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 (12 consecutive months without menses); in case of doubt a determination of serum follicle-stimulating hormone (FSH) can be done with FSH levels > 35 mIU/mL being confirmative for menopause.
10.Subjects will have to use highly effective contraceptive methods prior to the first dose of study drug, during the study, and for at least 12 weeks after the last dose of study drug.
a.If the subject is a sexually active woman of childbearing potential, she and her male partner are required to simultaneously use 2 effective contraceptive methods as listed in Section 4.2.4 of the protocol. Female subjects who use contraception must have done so for at least 14 days prior to the first dose of study drug.
b.Non-vasectomized male subjects with female partners of childbearing potential must be willing to use a condom in addition to having their female partner use another form of contraception as listed in Section 4.2.4 of the protocol.
11.Judged to be in good health, except for their CD, as determined by the investigator based upon the results of medical history, laboratory profile, physical examination, and a 12 lead electrocardiogram (ECG) performed during screening.
12.Able and willing to give voluntary written informed consent and meet all of the inclusion criteria and none of the exclusion criteria before being enrolled in the study. The subjects must sign the informed consent form prior to any study-related procedures and agree to the schedule of assessments.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1
Exclusion criteria:
1. History of sensitivity to any component of study drug, or a history of drug or other allergy that, in the investigator’s opinion, contraindicates subject’s participation in the study.
2. Suspicion of ulcerative colitis, indeterminate colitis, microscopic colitis, ischemic colitis, or radiation-induced colitis, based on medical history, endoscopy, and/or histological findings.
3. Any concurrent illness, condition, disability, or clinically significant abnormality
(including laboratory tests) that, in the investigator’s opinion, represents a safety risk for the subject’s participation in the study, may affect the interpretation of clinical safety or efficacy data, or may prevent the subject from safely completing the assessments required by the protocol, including:
a. Hb < 8.5 g/dL
b. WBC count < 3.0 x 10^9 cells/L
c. Neutrophil count < 1.5 x 10^9 cells/L
d. Platelet count < 100 x 10^9 cells/L
e. Serum ALT or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN)
f. Total bilirubin level > 1.5 x ULN, except in the case of documented Gilbert’s
syndrome
g. Creatinine clearance < 60 mL/min using the Cockroft formula.
4. 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.
5. History of active infections requiring intravenous antibiotics within the past 4 weeks prior to screening.
6. History of malignancy within the past 5 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).
7. History of bowel surgery within 6 months prior to screening Visit 1.
8. Presence or history of intestinal malignancy.
9. A history of significant psychological, neurologic, hepatic, renal, endocrine,
cardiovascular, GI (other than CD), pulmonary, or metabolic disease.
10. Presence of stoma, gastric or ileoanal pouch, proctocolectomy or total colectomy, symptomatic stenosis or obstructive strictures.
11. Bowel perforation in the last 6 months prior to screening Visit 1.
12. Treatment with:
a. TNFa inhibitor within 8 weeks prior to baseline
b. Vedolizumab within 12 weeks prior to baseline
c. Previous or current treatment with 6-thioguanine is prohibited
d. Methotrexate within 4 weeks prior to baseline
e. Natalizumab or biologic agent that depletes B or T cells within 12 months prior to baseline
f. Crohn’s disease–related antibiotics within 4 weeks prior to baseline
g. Cyclosporine, mycophenolate, tacrolimus, or interferon within 10 weeks prior to baseline
h. Topical corticosteroids, unless they are being used for other chronic inflammatory conditions, in which case, the subject may be included at the discretion of the investigator after discussion with the medical monitor
i. Rectally-applied medications (including 5-ASA) within 14 days before screening.
13. Regular use of probiotic or prebiotic preparations, if initiated or changed within 4 weeks prior to screening.
14. Regular daily use of oral nonsteroidal anti-inflammatory drugs, except low-dose aspirin (= 200 mg/day) for cardioprotection, within 7 days prior to screening.
15. Participation in another experimental therapy study within 90 days or 5 times the half-life of the experimental therapy, whichever is longer, prior to screening for this study or current enrollment in any other study.
16. History within the previous 2 years or current evidence of drug or alcoho

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Crohn’s Disease
MedDRA version: 17.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: GLPG1205
Product Code: G321605
Pharmaceutical Form: Capsule, hard
Current Sponsor code: G321605
Other descriptive name: GLPG1205
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Difference in CDAI change from baseline between GLPG1205- and placebo-treated subjects at Week 12

Main Objective: To demonstrate efficacy in terms of the change in Crohn’s Disease Activity Index (CDAI) score compared with baseline following 12 weeks of treatment with GLPG1205 100 mg once daily (qd) versus placebo in subjects with active moderate Crohn’s Disease (CD).

Secondary Objective: -To evaluate the safety and tolerability of GLPG1205 given to CD subjects for 12 weeks compared with placebo.
-To evaluate the efficacy in terms of percentage of subjects achieving CDAI clinical response and/or clinical remission with GLPG1205 given qd compared with placebo.
-To characterize the pharmacokinetics (PK) of GLPG1205 in CD subjects.
-To explore the effects of GLPG1205 on selected biomarkers (e.g., fecal calprotectin and C reactive protein [CRP]).

Timepoint(s) of evaluation of this end point: at Week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Weeks 4, 8, and 12; Fo Safety week 2 screening visit.

Secondary end point(s): Safety Endpoints:
- Frequency of Serious adverse events in GLPG1205 versus placebo
group.
- Frequency of Adverse events in GLPG1205 versus placebo group.
- Changes in physical examinations, vital signs, 12-lead ECG and
laboratory parameters over the duration of the study in GLPG1205
versus placebo group.
Efficacy endpoints:
- CDAI score at week 4, 8 and 12
- CDAI response at week 4, 8 and 12
- CDAI remission at week 4, 8 and 12

PK parameters:
GLPG1205 in blood at week 4, 8, 12

PD assessments:
- serum CRP in blood samples at baseline, week 4, 8 and 12 and FU
- fecal calprotectin in stool samples at screening, baseline, week 4, 8 and 12

Secondary ID(s)

2014-001892-30-HU

GLPG1205-CL-201

Source(s) of Monetary Support

Galapagos NV