E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
A form of inflammatory bowel disease |
|
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 | 18.0 |
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 |
|
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 |
Efficacy Objectives
Induction Phase
• To evaluate the efficacy of etrolizumab dose regimens compared with placebo in inducing CDAI remission, defined as a CDAI score < 150 at the end of the Induction Phase (Week 14)
Maintenance Phase
• To evaluate the efficacy of etrolizumab compared with placebo in maintaining corticosteroid (CS)-free CDAI remission for 1 year (52 weeks) among patients who achieved sustained CDAI remission at the end of the Induction Phase (Weeks 10 and 14)
Safety Objectives
• To evaluate the overall safety and tolerability of etrolizumab compared with placebo during Induction and Maintenance Phases of therapy
|
|
E.2.2 | Secondary objectives of the trial |
Evaluate in Induction Phase the efficacy of etrolizumab:
-dose regimens compared with placebo in inducing endoscopic improvement at Wk14, defined as a ≥50% reduction from the baseline SES-CD score
-dose regimens compared with placebo in inducing CDAI-100 response, defined as a decrease of at least 100 points from the baseline CDAI score at Wk14
-compared with placebo in achieving sustained induction of CDAI remission at Wks10 and 14
Evaluate in Maintenance Phase the efficacy of etrolizumab:
-dose regimens compared with placebo in achieving endoscopic improvement at Wk66 (compared to endoscopic score at Wk0), among patients achieving CDAI-70 response (defined as a decrease of at least 70 points from the baseline CDAI score) at Wk14
-compared with placebo in maintaining CDAI remission at Wk66, among patients achieving CDAI remission at Wk14
-compared with placebo in achieving CDAI-100 response at Wk66 (compared to CDAI at Wk0) among patients achieving CDAI-70 response at Wk14 |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The main protocol contains all details of the sub-study. There are no separate documents (with title, date and version) for the substudy. The objective of the substudy is to determine the relationship between etrolizumab exposure and receptor occupancy in peripheral blood in patients with CD. To achieve this objective, it is planned to enroll approximately 150 patients in the substudy. Blood sampling for the PK/PD substudy will continue in the Maintenance Phase. Patients in all cohorts will provide blood samples for population PK analysis and PD characterization. |
|
E.3 | Principal inclusion criteria |
- 18-80 years of age (inclusive)
- Moderately to severely active Crohn's disease as determined by the Crohn's Disease Activity Index (CDAI), patient reported outcomes and endoscopically defined disease activity in the ileum and/or colon
- Intolerance, loss of response or failure to respond to corticosteroids (CS) or, immunosuppressants (IS), or TNF inhibitors within the previous 5 years
- Use of effective contraception as defined by the protocol
|
|
E.4 | Principal exclusion criteria |
- A history of, or current conditions affecting the digestive tract, such as ulcerative colitis, indeterminant colitis, fistulizing disease, abdominal or perianal abscess, adenomatous colonic polyps, colonic mucosal dysplasia, and short bowel syndrome
- Planned surgery for CD
- Ileostomy or colostomy
- Has received non-permitted inflammatory bowel disease (IBD) therapies (including natalizumab, vedolizumab, and efalizumab, as stated in the protocol)
- Chronic hepatitis B or C infection, HIV, active or latent tuberculosis (patients with prior history of BCG vaccination must pass protocol-defined screening criteria)
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
a, Induction Phase
• Proportion of patients in CDAI remission
b, Maintenance Phase
• Proportion of patients in CS-free CDAI remission after ≥ 52 weeks of CS-free maintenance treatment, among patients who achieved CDAI remission at both Weeks 10 and 14.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
a, at Week 14
b, CDAI remission for this endpoint will be assessed at Weeks 66, 70, or 74 depending on the baseline CS dose level, and the required CS-free intervals |
|
E.5.2 | Secondary end point(s) |
Induction Phase
a, Proportion of patients with endoscopic improvement at Week 14
b, Proportion of patients who achieve CDAI-100 response at Week 14
c, Proportion of patients in CDAI remission at both Week 10 and Week 14
d, Changes from baseline to Week 14 in CD-PRO/SS score
e, Charges from baseline to Week 14 in IBDQ score
f, Proportion of patients in PRO2 remission at Week 14
Maintenance Phase
a, Proportion of patients with endoscopic improvement at Week 66, among CDAI-70 responders at Week 14
b, Proportion of patients who achieve CDAI remission at Week 66, among CDAI-remitters at Week 14
c, Proportion of patients who achieve CDAI remission at Week 66, among CDAI-70 responders at Week 14
d, Proportion of patients who achieve CDAI-100 response at Week 66
e, Proportion of patients in CDAI remission at Week 66 who have been CS-free for 24 weeks, among patients who achieved CDAI remission at Weeks 10 and 14
f, Proportion of patients in CDAI remission at Week 66 who have been CS-free for 24 weeks, among patients who achieved CDAI-70 response at Week 14
g, Proportion of patients in durable CDAI remission during the Maintenance Phase, among CDAI-70 responders at Week 14
h, Proportion of patients who maintain endoscopic improvement at Week 66 among patients who achieved endoscopic improvement and CDAI-70 response at Week 14
i, Resolution of mucosal inflammation (SES-CD score 0) at Week 66
j, Change from Week 14 to Week 66 in CD-PRO/SS score
k, Change from Week 14 to Week 66 in IBDQ score
l, Proportion of patients in PRO2 remission at Week 66, among patients who achieved PRO2 remission at Week 14 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Induction Phase
a, At Week 14
b, At Week 14
c, At both Week 10 and Week 14
d, From baseline to Week 14
e, From baseline to Week 14
f, At Week 14
Maintenance Phase
All evaluated at week 66 |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | No |
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 | 8 |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 200 |
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 |
Brazil |
Canada |
Israel |
Korea, Republic of |
Mexico |
New Zealand |
Russian Federation |
Serbia |
South Africa |
Switzerland |
Turkey |
Ukraine |
United States |
|
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 last patient’s last safety follow up visit that defined in the protocol of study GA29144, or the final visit for the last patient transferred to the OLE study (Study GA29145, Part 2), whichever is later.
|
|
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 | |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |