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 |
A form of inflammatory bowel disease. |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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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 evaluate the efficacy of etrolizumab (105 mg subcutaneous [SC] every 4 weeks [Q4W]) compared with placebo for the induction of remission as determined by the Mayo Clinic Score (MCS) at Week (W) 14.
• To evaluate the efficacy of etrolizumab (105 mg SC Q4W) compared with placebo for remission at W66 among patients with a clinical response at W14, as determined by the MCS. |
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E.2.2 | Secondary objectives of the trial |
• Clinical remission at W14 and W66
• Clinical response at W14
• Improvement in endoscopic appearance of the mucosa at W14 and W66
• Endoscopic and histologic remission at W14 and W66
• Change from baseline (BL) in rectal bleed and stool frequency subscore at W6
• Change from BL in UC bowel movement signs and symptoms and abdominal symptoms at W14 and W66, as assessed by Ulcerative Colitis Patient Reported Outcome Signs and Symptoms (UC-PRO/SS)
• Change from BL in Patient Reported health related Quality of Life at W14 and W66, as assessed by Inflammatory Bowel Disease Questionnaire (IBDQ)
• Clinical remission at W66 in patients in clinical remission at W14
• Remission at W66 among patients in remission at W14
• Corticosteroid (CS)-free clinical remission and remission at W66 in patients receiving CSs at BL
• Etrolizumab Serum Concentration
• Percentage of participants with Adverse Events
• Percentage of participants with Anti-Therapeutic Antibodies to Etrolizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Treatment within 5 years prior to screening with one or two induction regimens that contain TNF inhibitors (including TNF inhibitor biosimilars)
-18-80 years of age, inclusive.
- Diagnosis of UC established at least 3 months prior to Day 1
- Moderately to severely active ulcerative colitis (UC) as determined by the Mayo Clinic Score assessment (MCS).
- Washout of TNF inhibitor therapy for at least 8 weeks preceding Day 1.
- Background regimen for UC may include oral 5-aminosalicylic acid (5-ASA), oral corticosteroids, budesonide, probiotics, azathioprine (AZA), 6-
mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period.
- Use of highly effective contraception as defined by the protocol.
- Have received a colonoscopy within the past year or be willing to undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening.
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E.4 | Principal exclusion criteria |
- History of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic colitis, radiation colitis, or microscopic colitis, Crohn's disease, fistulas or abdominal abscesses, colonic mucosal dysplasia, intestinal obstruction, toxic megacolon, or unremoved adenomatous colonic polyps.
- Prior or planned surgery for UC.
- Past or present ileostomy or colostomy.
- Have received non-permitted inflammatory bowel disease (IBD) therapies (including natalizumab, vedolizumab, and efalizumab) as stated in the protocol.
- Any prior treatment with anti-adhesion molecules (e.g., anti-MAdCAM-1)
- Any treatment with tofacitinib during screening
- Congenital or acquired immune deficiency, chronic hepatitis B or C infection, Human Immunodeficiency Virus (HIV) positive, or history of tuberculosis (active or latent).
- Evidence of or treatment for Clostridium difficile within 60 days prior to Day 1 or other intestinal pathogens within 30 days prior to Day 1
- History of recurrent opportunistic infections, severe disseminated viral infections and organ transplant
- Any major episode of infection requiring treatment with intravenous (IV) antibiotics within 8 weeks prior to screening or oral antibiotics within 4 weeks prior to screening
- Received a live attenuated vaccine within 4 weeks prior to Day 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Remission at W 14, as determined by the Mayo Clinic Score (MCS).
2) Remission at W 66 among patients with clinical response at Week 14, as determined by MCS.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) at week 14
2) at week 66 |
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E.5.2 | Secondary end point(s) |
Percentage of participants in/with
1. Clinical remission at W14 and W66, as determined by MCS
2. Clinical response at W14, as determined by MCS
3. Improvement in endoscopic appearance of the mucosa at W14 and W66, as determined by Mayo Endoscopic Subscore
4. Endoscopic and histologic remission at W14 and W66, as determined by Mayo Endoscopic Subscore and Nancy Histological Index (NHI) respectively
5. Change from baseline in rectal bleed and stool frequency subscore at
W6, as determined by Mayo rectal bleeding and stool frequency Subscores respectively
6. Change from baseline in UC bowel movement signs and symptoms and
abdominal symptoms at W14 and W66, as assessed by UC-PRO/SS
7. Change from baseline in health-related Quality of Life at W14 and W66, as assessed by IBDQ
8. Clinical remission at W66 among patients in clinical remission at W14, as determined by MCS
9. Remission at W66 among patients in remission at W14, as determined by MCS
10. Corticosteroid (CS)- free clinical remission and remission at W66 in patients who were receiving CSs at baseline, as determined by MCS
11. Etrolizumab Serum Concentration
12. Adverse Events
13. Anti-Therapeutic Antibodies to Etrolizumab |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. W14, W66
2. W14
3-4. W14, W66
5. Baseline (Day-35- Day-1), W6
6-7. Baseline, W14, W66
8-9. W14 and W66
10. W66
11. Pre-dose (0 hour) on Day 1, Post-dose W14, W24, W44, W66, early
termination/end of safety follow-up (up to W78)
12. Baseline up to end of study (up to W78)
13. Pre-dose (0 hour) on Day 1, Post-dose W4, W14, W24, W44, W66,
early termination/end of safety follow-up (up to W78)
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Assessment of dynamic biomarker; retention of samples for genetic analysis; health-related quality of life (QOL) |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Cohort 1 (open label) and Cohort 2 (blinded) |
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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 | 5 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 151 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Hungary |
Israel |
Italy |
Korea, Republic of |
Lithuania |
Mexico |
Netherlands |
Poland |
Romania |
Spain |
Switzerland |
United Kingdom |
United States |
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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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The end of the study is defined as the last patient last safety follow-up visit in this protocol or last patient in this protocol transferred to the OLE-SM study (Study GA28951), whichever is later. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |