Placebo-controlled study to assess efficacy, safety and tolerability and to investigate the pharmacokinetics of GLPG1205 in subjects with moderate to severe Ulcerative Colitis

• Conditions: lcerative Colitis; MedDRA version: 18.0Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2014-001893-32-DE
• Lead Sponsor: Galapagos NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-09-24
• Last Update Posted: 2 May 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

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 UC (at least 6 months prior to baseline) as assessed by endoscopy and supported by histological assessment.
3. Allowed current UC treatment:
a. 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, if the dosage of = 30 mg prednisolone equivalent/day has been stable for at least 2 weeks prior to baseline and will be maintained at this dosage throughout the study.
4. Tumor necrosis factor alpha (TNFa) inhibitor–naive subjects should have failed at least 1 prior conventional therapy (e.g., ASAs, steroids, and/or immunomodulators).
5. Presence of active UC for a minimum period of 14 days prior to screening and spread beyond the rectum (inflammation extending = 15 cm from anal verge) as evidenced by clinical signs and endoscopy.
6. Mayo score = 6 and = 10 with rectal bleeding score = 1 and endoscopy score = 2 (confirmed by Core Imaging Laboratory).
7. 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.
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 (see Section 5.4.2).
10. Subjects will have to use highly effective contraceptive methods prior to the first dose of the study drug, during the study, and for at least 12 weeks after the last dose of the 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 the 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. 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 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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 the 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 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 109 cells/L
c. Neutrophil count < 1.5 x 109 cells/L
d. Platelet count < 100 x 109 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.
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 4 weeks prior to screening.
5. 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).
6. History of bowel surgery within 6 months prior to screening Visit 1.
7. Presence or history of intestinal malignancy (if any unexpected lesion/dysplasia is observed during screening endoscopy, additional biopsies should be taken for
histopathological assessment in the local laboratory, and recruitment into the study must be deferred until the results are available).
8. History of colon resection with < 30 cm of the colon remaining.
9. Suspicion of Crohn’s disease, indeterminate colitis, microscopic colitis, ischemic colitis, diverticular disease–associated colitis, or radiation-induced colitis, based on medical history, endoscopy, and/or histological findings.
10. A history of significant psychological, neurologic, hepatic, renal, endocrine,
cardiovascular, GI (other than UC), pulmonary, or metabolic disease.
11. Treatment with:
a. TNFa inhibitor within 8 weeks prior to baseline
b. Vedolizumab within 12 weeks prior to baseline
c. 6-Thioguanine within 4 weeks prior to baseline
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. Cyclosporine, mycophenolate, tacrolimus, or interferon within 10 weeks prior to baseline
g. 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
h. Rectally-applied medications (including 5-ASA) within 14 days before screening.
12. Regular use of probiotic or prebiotic preparations, if initiated or changed within 4 weeks prior to screening.
13. Regular daily use of oral nonsteroidal anti-inflammatory drugs, except low-dose aspirin (= 200 mg/day) for cardioprotection, within 7 days prior to screening.
14. 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.
15. Histor

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified