E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Ulcerative Colitis |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to Severe Ulcerative Colitis |
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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 itacitinib in inducing a Clinical Response in participants with moderate to severe Ulcerative Colitis. |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of itacitinib on endoscopic, clinical, and Quality of Life outcomes in participants with moderate to severe UC.
- To explore the safety and tolerability of itacitinib in participants with UC.
- To explore the PK of itacitinib in participants with UC. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participants must be ≥ 18 to < 75 years of age.
2. Have a confirmed diagnosis of UC at least 12 weeks before screening based on clinical, endoscopic, and histopathological evidence. A biopsy report supporting the diagnosis must be available in the participant's source documents.
3. Have a 3-component Mayo score of 4 to 9, which includes an mMES score of ≥ 2 as determined by a central reader, a rectal bleeding score of ≥ 1, and a stool frequency score of ≥ 1.
4. Participants must have failed or be intolerant to (discontinued the medication due to an AE as determined by the investigator) at least 1 of the following treatments for UC within 5 years of the screening visit:
a. Oral corticosteroids.
b. AZA or 6-MP.
c. Biologic therapy (eg, infliximab, vedolizumab, or adalimumab).
5. Participants currently receiving the following treatment(s) for UC are eligible, provided they have been receiving and are anticipated to continue on stable dose(s):
a. Oral 5-ASA (mesalamine up to 4.8 mg/kg per day) or sulfasalazine (up to 3 g/day) on a stable dose for at least 28 days before the screening visit and during the study.
b. Oral corticosteroids (less then 30 mg/day prednisone or oral corticosteroid equivalent) on a stable dose for at least 14 days before the screening visit and during the study, or, if started less than 8 weeks before the screening visit, must be on a stable dose for at least 4 weeks before the screening visit. |
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E.4 | Principal exclusion criteria |
1. Displaying clinical signs of fulminant colitis or toxic megacolon.
2. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical or radiographic findings suggestive of Crohn's disease.
3. Participants with disease limited to the distal 15 cm of the colon.
4. Participants receiving (or expected to receive) the following therapies within the designated timeframe below before the baseline visit or during the study:
a. 1 year (52 weeks): Anti-adhesion molecule therapy (eg, natalizumab, vedolizumab, or any investigational anti-adhesion molecule therapy).
b. 8 weeks:
− Anti-TNF therapy (eg, infliximab, adalimumab, golimumab, or certolizumab).
− Interferon therapy.
c. 4 weeks:
− Cyclosporine, mycophenolate, or tacrolimus.
− A daily dose of oral corticosteroids ≥ 30 mg prednisone or equivalent.
− Intravenous corticosteroids.
d. 2 weeks:
− Rectally administered formulation of corticosteroids or 5-ASA.
− AZA, 6-MP, or methotrexate |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants with a Clinical Response 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) |
• Proportion of participants with Endoscopic Response at Week 12.
• Proportion of participants with Mucosal Healing at Week 12.
• Proportion of participants in Endoscopic Remission at Week 12.
• Proportion of participants in Clinical Remission at Week 12.
• Proportion of participants in each category (0, 1, 2, or 3) for each of the 3‐component Mayo subscores (stool frequency, rectal bleeding, mMES).
• Change from baseline at Week 12 in 3-component Mayo score.
• Change from baseline to Week 12 in PGA score.
• Change in Quality of Life score as measured by the IBDQ at Weeks 4 and 12.
Monitoring the incidence, duration, and severity of AEs; performing physical examinations; collecting vital signs; and collecting ECGs and laboratory data for hematology, serum chemistry, and urinalysis.
• Plasma concentrations of itacitinib at Weeks 2, 4, and 12 for determination of Cmin, Cmax and, data permitting, AUC0-τ, CL/F, Vz/F, half-life, and Tmax.
• Stool concentrations of itacitinib at Week 4 following 24-hour collection. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
double-blind, randomized, placebo-controlled period followed by open label period |
|
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 | 6 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
United States |
Czechia |
Germany |
Poland |
Romania |
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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
|
The end of the study is defined as the date of the last visit of the last participant in the study. |
|
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 | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |