A Study to Investigate the Efficacy and Safety of the study drug, GLPG0634, in Subjects With Active Crohn’s Disease With Evidence of Mucosal Ulceration

• Register: EUCTR
• Last refreshed on: 28 November 2016
• Main ID: EUCTR2013-002857-32-DE
• Date of registration: 30/10/2013
• Prospective Registration: Yes
• Primary sponsor: Galapagos NV
• Public title: A Study to Investigate the Efficacy and Safety of the study drug, GLPG0634, in Subjects With Active Crohn’s Disease With Evidence of Mucosal Ulceration
• Scientific title: Double-Blind, Randomized, Placebo-Controlled, Multi Centre Study to Investigate the Efficacy and Safety of GLPG0634 in Subjects With Active Crohn’s Disease With Evidence of Mucosal Ulceration
• Date of first enrolment: 20/02/2014
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002857-32
• 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: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 7
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, France, Germany, Hungary, Poland, Romania, Russian Federation, 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 subjects between the ages of 18 and 75 years, on the day of signing informed consent.
2. Documented history of ileal, colonic, or ileocolonic CD (at least 3 months prior screening) 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 inflammation at screening as demonstrated by endoscopic confirmation of active disease (based on central reading) with evidence of ulceration corresponding to a score of 1 in at least 1 of the 5 ileocolonic segments on Presence of Ulcers subscore of the Simplified Endoscopy Score for CD (SES CD) and total score of at least 7.
5. Treatment with oral steroids (= 30 mg prednisolone equivalent/day) or budesonide dose = 9mg/day) is allowed, if at a stable dose since at least 2 weeks prior to the first dose of study drug.
6. Subjects previously not exposed to anti-TNF treatment or subjects previously exposed to anti-TNF therapy at a dose registered for the treatment of CD that has been discontinued at least 8 weeks prior to Baseline. Subjects deemed by the treating physician as a primary or secondary non-responder or intolerant to anti-TNF treatment or responders to anti-TNF treatment, where treatment was stopped for other reasons (TNF-experienced) can also be included.
7. Subjects are allowed to continue on concurrent treatment with the following agents:
a) Mesalazine and olsalazine if stable dosage for at least 4 weeks prior to Screening (same dosage to be maintained throughout the study). Previous exposure to sulfasalazine is permitted but must be discontinued at least 4 weeks prior to Screening in male subjects.
b) Crohn’s Disease-related antibiotics if stable dosage for at least 4 weeks prior to Screening and no discontinuation in the 14 days prior to the first dose of study drug
c) Probiotics if stable dosage for 2 weeks prior to the first dose of study drug.
8. Previous exposure to immunomodulators is permitted, but must be discontinued (and agreed by the subject) at least 25 days prior to to the first dose of the study drug. Subjects whose Immunomodulators were discontinued prior to Screening are also permitted to participate. Documented evidence for the reasons of discontinuation should be provided.
9. The results of the following laboratory tests during screening must be as specified below:
a) Haemoglobin = 9 g/dL (International System of Units [SI]: = 90 g/L)
b) White blood cells = 3.0 x 109 cells/L
c) Neutrophils = 2.0 x 109 cells/L
d) Lymphocytes = 0.5 x 109 cells/L
e) Platelets = 100 x 109 cells/L
f) Serum alanine transaminase and aspartate transaminase = 1.5 x ULN
g) Total bilirubin level = 1.5 x ULN
h) Alkaline phosphatase =1.5 x ULN
i) Lipase = 1.5 x ULN and amylase = 1.5 x ULN
j) Creatinine clearance > 60 mL/min and blood urea nitrogen within normal ranges. Creatinine clearance will be calculated using the Cockroft-Gault formula.
10. Women of childbearing potential 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 confirming menopause status.
11. Subjects willing to use highly effective contraceptive methods prior to the first dose of the study drug, during the study and for at leas
Exclusion criteria:
1. Diagnosis of indeterminate colitis, ulcerative colitis (UC), or clinical findings suggestive of UC.
2. Stoma, gastric or ileanal pouch, proctocolectomy or total colectomy, symptomatic stenosis or obstructive strictures, abscess or suspected abscess, history of bowel performation.
3. Subject who has had surgical bowel resections within the past 6 months or is planning any resection at any time point while enrolled in the study.
4. Subject who has short bowel syndrome.
5. Subject who is receiving tube feeding, defined formula diets, or total parenteral alimentation.
6. Subject with positive Clostridium difficile toxin stool assay or test positive for stool culture of enteric pathogens, ova of parasites during the screening period.
7. Subject has received nonsteroidal anti-inflammatory drugs within 14 days prior to Screening or during screening period.
8. Subject has received therapeutic enema or suppository, other than required for colonoscopy, within 7 days prior to or during screening period.
9. Subject has received intravenous corticosteroids within 14 days prior to Screening or during screening period.
10. If nonsystemic steroids are being used for other conditions than CD, subjects may be included at the discretion of the Investigator after discussion with the Medical Monitor.
11. Treatment with cyclosporine, mycophenolate mofetil, tacrolimus, or interferon within 10 weeks prior to Screening or during screening period.
12. Any prior treatment with lymphocyte-depleting agents. Subjects who have previously received either lymphocyte apheresis or selective monocyte granulocyte apheresis within 12 months prior to Screening and during the study.
13. Subjects who have previously received fecal microbiota transplants or stem cell transplantation.
14. Subjects who have received previous treatment with investigational chemical agents within 4 weeks prior to Screening.
15. Subjects who have previously received treatment with biological IMPs including murine, chimeric or humanized monoclonal antibodies or a chemokine receptor blocker within less than 5 half-lives prior to Baseline. Previous treatment with a janus kinase inhibitor is prohibited.
16. Known hypersensitivity to study drug ingredients or a significant allergic reaction to any drug as determined by the Investigator, such as anaphylaxis requiring hospitalization.
17. Subject with a previous history of dysplasia of the GI tract (high or low grade, flat or raised including discrete adenoma-like dysplasia or indefinite dysplasia) or found to have above described dysplasia in any biopsy performed during the screening colonoscopy.
18. Concurrent GI malignancy or a history of cancer elsewhere (other than basal cell carcinoma or carcinoma in situ of the cervix successfully treated more than 5 years prior to the initial study drug administration).
19. History of, or signs and symptoms suggestive of, lymphoproliferative disease including lymphadenopathy or splenomegaly.
20. Positive serology for 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.
21. Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks of the Screening visit or completion of oral anti-infectives within 2 weeks of the Screening visit (except Crohn’s disease related antibiotics). Immunocomprom

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

Health Condition(s) or Problem(s) studied

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

Crohn’s Disease With Evidence of Mucosal Ulceration
MedDRA version: 18.1 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Intervention(s)

Product Name: GLPG0634
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FILGOTINIB
CAS Number: 1206161-97-8
Current Sponsor code: GLPG0634
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Clinical remission defined as CDAI < 150 at Week 10.

Main Objective: To demonstrate efficacy in terms of the percentage of subjects achieving clinical remission (CD Activity Index [CDAI] score < 150) following 10 weeks treatment with GLPG0634 200 mg q.d. versus placebo in patients with active CD with evidence of mucosal ulceration.

Timepoint(s) of evaluation of this end point: Week 10

Secondary Objective: To evaluate the efficacy in terms of percentage of subjects achieving clinical response, clinical remission, endoscopic response, endoscopic remission and mucosal healing with GLPG0634 given once daily compared to placebo.

To assess the effect of GLPG0634 (compared to placebo) on subject’s quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ).

To evaluate the safety and tolerability of GLPG0634 given to CD subjects.

To characterize the pharmacokinetics (PK) of GLPG0634 and its metabolite (G254445) in CD subjects.

To assess the effects of GLPG0634 on selected pharmacodynamic (PD)/biomarkers (eg, C-reactive protein [CRP], faecal calprotectin, serum analytes/miRNA, whole blood gene expression/miRNA, faecal microbiota).

To evaluate the effect of GLPG0634 on histopathological features of the intestinal mucosa.

To develop an exposure-response model between GLPG0634/G254445 exposure and selected pharmacodynamic (PD)/biomarkers or efficacy markers.

Secondary Outcome(s)

Secondary end point(s): Clinical remission, clinical response, endoscopic response, endoscopic remission and mucosal healing, changes from baseline in CDAI score, SES-CD score, histopathology scores, IBDQ score, and in CDAI subscores (pain, liquid stools, and general well-being), and the time to first response with GLPG0634 given once daily in comparison to placebo.

Timepoint(s) of evaluation of this end point: Each visit.

Secondary ID(s)

GLPG0634-CL-211

Source(s) of Monetary Support

Galapagos NV