| 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 |
| Crohn's disease is a disease that causes the intestines to become swollen and may develop ulcers |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10011402 |
| E.1.2 | Term | Crohn's disease (colon) |
| E.1.2 | System Organ Class | 100000004856 |
|
| 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 |
Stage 1: To compare the efficacy of brazikumab with that of placebo to achieve endoscopic response and clinical remission at Week 12
Stage 2: To compare the efficacy of brazikumab with that of Humira® to achieve endoscopic response and clinical remission at Week 52 in participants who are BM+ |
|
| E.2.2 | Secondary objectives of the trial |
Stage 1:
To compare the efficacy of brazikumab with that of placebo to achieve sustained endoscopic response and clinical remission at both Wk12 and Wk52
To compare the efficacy of brazikumab with that of placebo to achieve endoscopic remission and clinical remission at Wk52
To compare the efficacy of brazikumab with that of placebo to achieve endoscopic response at Week 12 and endoscopic remission at Wk52 and clinical remission at both Wk12 and Wk52
Stage 2:
To compare the efficacy of brazikumab with that of Humira® to achieve sustained endoscopic response and clinical remission at both Wk12 and Wk52 in participants who are BM+
To compare the efficacy of brazikumab with that of Humira® to achieve endoscopic remission and clinical remission at Wk52 in participants who are BM+
To compare the efficacy of brazikumab with that of Humira® to achieve CS free (for the last 12 wks before the assessment at Wk 52) endoscopic and clinical remission at Wk 52 in participants who are BM+ |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Aged 18 to 80 years, inclusive.
2. Diagnosis of ileal, ileocolonic, or colonic CD with an onset of symptoms for a minimum of 3 months prior to Screening as determined by the investigator based on clinical history, exclusion of other etiologies including infectious causes, and characteristic endoscopic and/or histologic findings.
3. Moderately to severely active CD
4. Participant had an inadequate response or intolerance to intervention with oral aminosalicylates, oral CS, azathioprine, methotrexate, or 6-mercaptopurine, or demonstrated CS dependence for the treatment of CD.
5. Participants taking 5-aminosalicylates, Oral prednisone (or equivalent), Budesonide, Immunomodulators, Oral antibiotics, Probiotics must be at a stable dose.
6. Meets the following TB criteria: Participant has no known history of active TB; Participant has no known history of latent TB without completion of an appropriate course of intervention or is presently taking appropriate ongoing prophylactic intervention; Meets 1 of the following acceptable TB test results: Negative QFT-TB obtained from central laboratory within 4 weeks prior to randomization or For a positive QFT-TB test obtained during Screening from the central laboratory, active TB must be ruled out or Indeterminate QFT-TB test obtained during the Screening period from the central laboratory with ongoing QFT-TB testing; A negative tuberculin skin test is required if the QFT-TB test is not approved/registered in that country; Participants with a history of using anti-TNFα agents for a treatment course of 1 year or longer who have discontinued an anti-TNFα agent within 6 months prior to Screening must obtain a chest x-ray showing no evidence of active TB within 8 weeks prior to Screening or during Screening.
7. Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 acceptable methods of contraception from Screening.
8. Female participants who are post-menopausal and of non-childbearing potential must have an elevated FSH at or above the range for post-menopausal women by the central laboratory during Screening.
9. Nonsterilized males who are sexually active with a female partner of childbearing potential must comply with the methods of contraception
10. Ability to provide written informed consent prior to any study procedures
11. Willingness and ability to attend all study visits, comply with the study procedures, read and write in order to complete questionnaires, and be able to complete the study period
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|
| E.4 | Principal exclusion criteria |
1. Participant has previously received Humira® and was intolerant to treatment or had met the criteria for primary or secondary non-response to treatment:
a. Primary non-response: Signs and symptoms of persistently active disease despite a history of at least 1 induction regimen of Humira® per the local label consisting of at least 2 doses at least 2 weeks apart
b. Secondary non-response: Recurrence of symptoms of persistently active disease during scheduled maintenance dosing of Humira® per the local label following prior clinical benefit
c. Intolerance: AE associated with discontinuation of Humira® therapy, including, but not limited to, hypersensitivity, infusion-related reaction, infection, or congestive heart failure
2. Participant is unable or unwilling to have endoscopic procedures performed during the study.
3. History or current diagnosis of ulcerative colitis, indeterminate colitis, microscopic colitis, ischemic colitis, colonic mucosal dysplasia, primary sclerosing cholangitis, or untreated bile acid malabsorption.
4. History of toxic megacolon within 3 months prior to Baseline (Visit 2).
5. Any intra-abdominal surgery, bowel resection, diversion, placement of ostomy or stoma within 3 months prior to Screening. Participants with a draining stoma are excluded.
6. Participant has an enterocutaneous or entovesicular fistula. Participants with active fistulas may be considered if there is no anticipation for surgery and there is no evidence of active infection (eg, abscess) after further discussion with the study medical monitor.
7. Bowel perforation during the 6 months prior to Screening or evidence of obstruction within 3 months of Screening.
8. Complications of CD including short bowel syndrome, strictures/stenoses with obstruction or pre-stenotic dilation, or conditions where surgery may be anticipated within 6 months, or other conditions that may confound efficacy evaluations for the study.
9. Participant has any non-passable colonic stenosis/narrowing identified during the qualifying ileocolonoscopy (successful endoscope passage to the caecum with inability to enter the endoscope into the ileum is not covered under this exclusion criterion, and does not require exclusion).
10. Ongoing nutritional dependency for total parenteral nutrition or an elemental diet at Screening.
11. Participant has any of the following related to infections:
a. Evidence of a recent (within 6 months of Baseline [Visit 2]) systemic fungal infection, requiring inpatient hospitalization, and/or antifungal treatment. Participants treated for localized fungal infections (eg, oral, vaginal, and skin candidiasis, onychomycosis) are not excluded.
b. Any infection requiring hospitalization or treatment with IV anti-infectives (including anti-viral treatment) within 4 weeks of Screening
c. Cytomegalovirus or Epstein-Barr virus infection that has not completely resolved within 8 weeks prior to Screening
d. Clinically significant chronic infection (eg, osteomyelitis) that has not resolved within 8 weeks of Screening
e. Non-serious infection requiring oral anti-infectives within 2 weeks prior to randomization must be further discussed with the study medical monitor. Chronic suppressive antiviral treatment for herpes simplex virus in the absence of active lesions or uncomplicated urinary tract infections are not considered exclusionary.
f. Participant has clinical evidence of or suspected to have an abscess during Screening. Cutaneous and perianal/perirectal abscesses are not exclusionary if drained and adequately treated at least 3 weeks prior to Screening.
g. Diagnosis of peritonitis or receiving treatment for peritonitis within 8 weeks prior to Screening
h. Participant has any underlying condition that predisposes participant to infections
12. Previous allogenic bone marrow transplant or history of organ or cell-based transplantation (eg, islet cell transplantation or autologous stem cell transplantation) with the exception of corneal transplant.
13. Chronic hepatitis B or C infection, TB, or C. difficile-positive at Screening (Visit 1).
14. Known history of primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, including HIV infection. Participants with positive results of HIV testing by the central laboratory will be excluded.
15. Prior history of or current diagnosis of a demyelinating disorder.
All exclusion criteria cannot be list in this field, please refer to the section 5.2 of the protocol
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Stage 1:
a. Endoscopic response
b. Clinical remission
Stage 2:
a. Endoscopic response
b. Clinical remission
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Stage 1:
a. at Week 12: Minimum of 50% decrease from Baseline in SES‑CD total score
b. at Week 12: Average daily LSF subscore of ≤ 3 as assessed on the CDAI LSF item AND
Average daily AP subscore of ≤ 1 as assessed on the CDAI AP item
Stage 2:
a. at Week 52
b. at Week 52 |
|
| E.5.2 | Secondary end point(s) |
Stage 1:
a. Endoscopic response
b. Clinical remission
c. Endoscopic remission
d. Clinical remission
e. Endoscopic response and endoscopic remission
f. Clinical remission
Stage 2:
a. Endoscopic response
b. Clinical remission
c. Endoscopic remission
d. Clinical remission
e. CS-free endoscopic remission
f. CS-free clinical remission |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Stage 1:
a. at both Week 12 and Week 52
b. at both Week 12 and Week 52
c. at Week 52
- SES-CD total score of 0-2 OR
- SES-CD total score of ≤ 4 and at least 2‑point reduction from Baseline with no
subscore > 1
d. at Week 52
e. at Week 12 and at Week 52
f. at both Week 12 and Week 52
Stage 2:
a. at both Week 12 and Week 52.
b. at both Week 12 and Week 52
c. at Week 52
d. at Week 52
e. at Week 52
f. at Week 52
|
|
| 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 | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | 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 |
| Double Dummy, Operationally Seamless |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 180 |
| 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 |
| Austria |
| Belgium |
| Bulgaria |
| Canada |
| Czech Republic |
| France |
| Germany |
| Hungary |
| Israel |
| Italy |
| Poland |
| Romania |
| Russian Federation |
| South Africa |
| Spain |
| Ukraine |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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