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 compared with placebo for remission at Week (W) 62 among patients with a clinical response at W 10 |
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E.2.2 | Secondary objectives of the trial |
To evaluate • Maintenance of clinical remission and remission at W 62 for patients in clinical remission and remission at W 10 • Clinical remission at W 62 • Remission at W62 among patients in remission at W10 • Improvement in endoscopic appearance of the mucosa at W 62 • Endoscopic remission at W 62 • Histologic remission at W 62 • Onset of action, defined as change from baseline in rectal bleed and stool frequency subscore at W 6 • Corticosteroid free clinical remission and remission at W 62 in patients who were receiving corticosteroids at baseline • Change from baseline to W 62 in UC bowel movement signs and abdominal symptoms, as assessed by UC Patient-Reported Outcome (PRO) Signs and Symptoms measure • Change from baseline to W 62 in patient-reported health-related quality of life (QOL), as assessed by Inflammatory Bowel Disease Questionnaire (IBDQ) score • Etrolizumab serum concentration • Overall safety and tolerability of etrolizumab over a period of 62 weeks |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 18-80 years of age, inclusive. • Diagnosis of UC established at least 3 months prior to Day 1 by clinical and endoscopic evidence. • Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS) • Evidence of UC extending a minimum of 20 cm from the anal verge as determined by baseline endoscopy • Naive to treatment with any anti-TNF therapy •Patients must have an inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment • 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 • Must 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 |
- A 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 prior treatment with rituximab - 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) |
Remission at W 62 among patients with a clinical response at W 10 as determined by MCS and concomitant treatment
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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) |
1) Proportion of patients in clinical remission at W 62 among patients in clinical remission at W 10 2) Proportion of patients in clinical remission at W 62 3) Proportion of patients in remission at W 62 among patients in remission at W 10 4) Proportion of patients with Improvement in endoscopic appearance of the mucosa at W 62 5) Proportion of patients in Endoscopic remission at W 62 6) Proportion of patients in Histologic remission at W 62 7) Change from baseline in rectal bleed subscore at W 6 8) Change from baseline in stool frequency subscore at W 6 9) Proportion of patients in Corticosteroid free clinical remission at W 62 in patients who are receiving corticosteroids at baseline 10) Change from baseline to W 62 in UC bowel movement signs and symptoms as assessed by the UC PRO/SS measure 11) Change from baseline to W 62 in UC abdominal symptoms as assessed by the UC PRO/SS measure 12) Change from baseline to W 62 in patients' health related QOL as assessed by the overall score of the IBDQ score 13) Incidence and severity of adverse events and serious adverse events 14) Incidence and severity of infection and serious infection-related adverse events 15) Incidence and severity of injection site reactions 16) Incidence of adverse events leading to study drug discontinuation 17) Incidence and severity of hypersensitivity reaction events 18) Incidence of laboratory abnormalities 19) Incidence of malignancies 20) Incidence of ATAs to etrolizumab 21) Serum trough concentration at steady state during the dosing period from W 12 to W 62 22) Serum concentration at primary endpoint time (W 62) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-6) W 62 7-8) Baseline (Day 1) to W 6 9) W 62 10-12) Baseline to W 62 13-19) Up to W 62 20).W 0, W 4, W 12, W 24, W 44, W 62, unscheduled visit and at early withdrawal from treatment visit 21) From W 12 to W 62 22) At W 62 |
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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 |
biomarkers analyisis; 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 |
10 wks open label induction treatment; 52 wks double-blind maintenance treatment |
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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 | 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 | 38 |
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 |
Brazil |
Canada |
Czech Republic |
Denmark |
Germany |
Hungary |
Israel |
Italy |
Mexico |
Poland |
Slovakia |
South Africa |
Ukraine |
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 enrolled in the OLE-SM study, 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 |