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

• Register: EUCTR
• Last refreshed on: 16 November 2015
• Main ID: EUCTR2014-001893-32-HU
• 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 to severe Ulcerative Colitis
• 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 to Severe Ulcerative Colitis
• Date of first enrolment: 08/12/2014
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001893-32
• 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: no Other: yes Other trial design description: exploratory proof-of-concept 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, Germany, Hungary, Poland, Russian Federation

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 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 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

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

Health Condition(s) or Problem(s) studied

Ulcerative Colitis
MedDRA version: 18.0 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

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): -Actual values, changes from baseline, and percent changes from baseline.
-Percentage of subjects achieving Mayo clinical remission at Week 8 as measured by Mayo score in the GLPG1205 group versus the placebo group (Mayo score = 2 with no individual subscore exceeding 1 point and rectal bleeding score of 0).Change in Mayo of GLPG1205 vs placebo at week 8 compared to baseline .
-Percentage of subjects achieving Mayo clinical response at Week 8 as measured by Mayo score in the GLPG1205 group versus the placebo group (reduction from baseline Mayo score of 30% or = 3 points, with an accompanying decrease in rectal bleeding subscore of = 1 point or absolute rectal bleeding score of = 1 point).
-Endoscopic response rate at Week 8, defined as proportion of subjects with endoscopy score (i.e., Mayo endoscopy subscore) decreased by = 1 point in comparison with baseline.
-Mucosal healing rate at Week 8, defined as proportion of subjects with endoscopy score (i.e., Mayo endoscopy subscore) of 0 or 1.

Secondary Objective: -To explore the efficacy of GLPG1205 versus placebo in UC subjects by use of the partial Mayo score comparing results to baseline.
- To explore the efficacy of GLPG1205 versus placebo in UC subjects by use of the histopathological Geboes index comparing results at Week 8 to baseline.
-To evaluate the safety and tolerability of GLPG1205 given to moderate to severe UC subjects for 12 weeks compared to placebo.
-To characterize the PK of GLPG1205 in UC subjects.
-To explore the effects of GLPG1205 on selected biomarkers (e.g., fecal calprotectin, myeloperoxidase (MPO), C-reactive protein [CRP]).

Main Objective: To explore the efficacy of GLPG1205 versus placebo in UC subjects by use of the Mayo score comparing results at Week 8 to baseline.

Timepoint(s) of evaluation of this end point: Week 8

Secondary Outcome(s)

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:
- Partial Mayo at week 4, 8, 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
- MPO in biopsy samples at baseline and week 8
- Geboes Index at week 8
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
- MPO in biopsy samples at baseline and week 8

Timepoint(s) of evaluation of this end point: Weeks 4,8,12 and week 2 for safety

Secondary ID(s)

GLPG1205-CL-211

2014-001893-32-CZ

Source(s) of Monetary Support

Galapagos NV