E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
-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]).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (TNFα) 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.
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E.4 | Principal 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. TNFα 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 alcohol abuse at the discretion of the investigator.
17. Pregnant or lactating women.
18. Medical, psychiatric, cognitive, or other conditions that, according to investigator’s medical judgment, compromise the subject's ability to understand the subject information, give informed consent, comply with the requirements of the study protocol (that is likely to affect the subject’s return for visits on schedule), or complete the study.
19. If applicable to national or local legislation, a history of being admitted to an institution under an administrative or court order. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in CDAI change from baseline between GLPG1205- and placebo-treated subjects at Week 12 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 4, 8, and 12; Fo Safety week 2 screening visit. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Czech Republic |
France |
Germany |
Hungary |
Poland |
Russian Federation |
Spain |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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last contact with the last subject in the study |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |