| 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 condition that affects the lining of the digestive tract due to inflammation and may result in ulcers and/or strictures. |
|
| 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 CDAI 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 |
Stage1Compare efficacy of brazikumab (IMP) with placebo
•endoscopic response, CDAI response, clinical remission [W(week)12]
•CDAI remission, CDAI response, endoscopic response, clinical remission (W12 and W52)
•CDAI remission, CDAI response, endoscopic response, SES-CD total score of 0-2, endoscopic remission, clinical remission (W52)
•endoscopic response (W12) and endoscopic remission (W52)
•Establish serum IL22 concentration Baseline clinical cutoff value to predict IMP efficacy
Stage2(BM+ patients)
Compare efficacy of IMP with Humira
•endoscopic response, clinical remission (W12andW52)
•endoscopic remission, clinical remission (W52)
•CS-free endoscopic remission, clinical remission (W52)
And in patients taking CS at baseline
•endoscopic response, clinical remission (W12)
•endoscopic response (W12), endoscopic remission (W52), clinical remission (W12,52)
Stage 1and2
Evaluate IMP PK, immunogenicity, safety, tolerability
Characterize IMP exposure-response relationship |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1 At the time of signing the informed consent, the participant must be 18 to 80 years of age, inclusive.
2 A 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 conventional treatment [oral aminosalicylates, oral CS, azathioprine, methotrexate, or 6-mercaptopurine], or prior biological treatment, or demonstrated CS dependence for the treatment of CD. For participants who have previously used biological treatment, a participant may have failed up to 3 biologics that include up to 2 different mechanisms of action.
5 Participants taking 5-aminosalicylates, Oral prednisone (or equivalent), Budesonide, Immunomodulators, Oral antibiotics, Probiotics must be at a stable dose.
6 No known history of active TB or latent TB without completion of appropriate intervention.
7 Female participants of childbearing potential must have a negative urine pregnancy test prior to administration of study intervention and must agree to use a highly effective method of birth control (confirmed by the investigator) from randomization throughout the study duration and for at least 18 weeks after last dose of study intervention.
8 Women not of childbearing potential are defined as women who are either permanently sterilized or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomization without an alternative medical cause.
9 Nonsterilized males who are sexually active with a female partner of childbearing potential must comply with the methods of contraception during treatment and until the end of relevant systemic exposure in the male participant, plus a further 18 weeks.
10 Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
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.
For all detailed Inclusion criteria please refer to the section 5.1 of the protocol. |
|
| E.4 | Principal exclusion criteria |
1 Participant is unable or unwilling to have endoscopic procedures performed during the study.
2 History or current diagnosis of ulcerative colitis, indeterminate colitis, microscopic colitis, ischemic colitis, colonic mucosal dysplasia, primary sclerosing cholangitis, or untreated bile acid malabsorption.
3 History of toxic megacolon within 3 months prior to Randomization (Day 1).
4 Any intra-abdominal surgery, bowel resection, diversion, placement of ostomy or stoma within 3 months prior to Screening. Participants with a draining stoma, ostomy, or extensive colonic resection are excluded.
5 Participant has an enterocutaneous or enterovesicular fistula. Participants with other active fistulas, including perianal fistulas, may be considered for enrollment if there is no anticipation for surgery and there is no evidence of active infection (eg, abscess).
6 Bowel perforation during the 6 months prior to Screening or evidence of obstruction within 3 months of Screening.
7 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.
8 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).
9 Ongoing nutritional dependency for total parenteral nutrition or an elemental diet at Screening.
10 Participant has any of the following related to infections:
• Evidence of a recent (within 6 months of Randomization [Day 1]) systemic fungal infection, requiring inpatient hospitalization, and/or antifungal treatment.
• Any infection requiring hospitalization or treatment with IV anti-infectives (including antiviral treatment) within 4 weeks of Screening.
11 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.
12 Chronic hepatitis B or C infection defined as:
• Hepatitis B: positive for hepatitis B surface antigen (HBsAg+) or positive for anti–hepatitis B core antibody (HBcAB+) and positive confirmatory PCR for HBV, regardless of anti–hepatitis B surface antibody status
• Hepatitis C: positive result for hepatitis C antibody and positive confirmatory PCR test for hepatitis C virus
13 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.
14 Participant has received the following treatment:
• Adalimumab, certolizumab pegol, infliximab, or golimumab: within 8 weeks prior to Randomization (Day 1)
• Vedolizumab or ustekinumab within 12 weeks prior to Randomization (Day 1)
• Other prohibited medication, biologic or small molecule treatment within 5 half-lives prior to Randomization (Day 1)
• Fecal microbiota transplantation: within 8 weeks prior to Screening ileocolonoscopy
15 Except for ustekinumab, prior exposure to any biologic agent targeting IL-12 or IL-23.
All exclusion criteria with all details 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. CDAI 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
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. CDAI response
D. CDAI remission
E. CDAI response
F. Endoscopic response
G. Clinical remission
H. Endoscopic remission
I. Clinical remission
J. CDAI response
K. CDAI remission
L. Endoscopic response
M. SES-CD total score of 0-2
N. Endosopic response, endoscopic remission
O. Population PK model of serum concentrations of brazikumab and analysis for serum anti-brazikumab antibodies
P. Exposure-response model linking primary endpoint to metrics of model-predicted individual brazikumab exposures
Q. Exploration of relationship of Baseline serum IL-22 concentration with efficacy of brazikumab and establishment of the serum IL-22 concentration clinical cutoff to stratify participants in Stage 2 through CDAI remission and endoscopic response.
R. AEs, clinical laboratory values, vital signs, physical exams, ECGs
Stage 2:
A. Endoscopic response
B. Clinical remission
C. Endoscopic remission
D. Clinical remission
E. CS-free endoscopic remission
F. CS-free clinical remission
G. CS-free endoscopic remission for participants taking CS at Baseline
H. CS-free clinical remission for participants taking CS at Baseline
I. Endoscopic response
J. Clinical remission
K. Endoscopic response, endoscopic remission
L. Clinical remission
M. Endoscopic response
N. Clinical remission
O. Population PK model of serum concentrations of brazikumab and analysis for serum anti-brazikumab antibodies
P. Exposure-response model linking primary endpoints to metrics of model-predicted individual brazikumab exposures
Q. Adverse events, clinical laboratory values, vital signs, physical exams, ECGs |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Stage 1:
A. at Week 12
B. at Week 12
C. at Week 12
D. at both Week 12 and Week 52
E. at both Week 12 and Week 52
F. at both Week 12 and Week 52
G. at both Week 12 and Week 52
H. at Week 52
I. at Week 52
J. at Week 12
K. at Week 52
L. at Week 52
M. at Week 52
N. Week 12, Week 52
O. Up to Week 52
P. Up to Week 52
Q. at Week 12
R. Up to 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
G. at Week 52
H. at Week 52
I. at Week 12
J. at Week 12
K. at week 12 and Week 52
L. at both Week 12 and Week 52
M. at Week 52
N. at Week 52
O. Up to Week 52
P. Up to Week 52
Q. Up to 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 | No |
| 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 | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| 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 | 78 |
| 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 |
| Canada |
| China |
| India |
| Israel |
| Korea, Republic of |
| Russian Federation |
| South Africa |
| Taiwan |
| Ukraine |
| United States |
| Austria |
| France |
| Germany |
| Hungary |
| Italy |
| Poland |
| Slovakia |
| Spain |
| United Kingdom |
| Czechia |
|
| 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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