Clinical Trials List
Protocol NumberD5271C00001 (Legacy # 3150-301-008)
Completed
2020-04-01 - 2024-06-12
Phase II/III
Not yet recruiting3
Recruiting6
A 52-Week, Multicenter, Randomized, Double-Blind, Placebo and Active-Controlled, Operationally Seamless Phase 2b/3, Parallel-group Study to Assess the Efficacy and Safety of Brazikumab in Participants With Moderately to Severely Active Crohn’s Disease (INTREPID Lead-In)
-
Trial Applicant
-
Sponsor
AstraZeneca AB
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 王賀立 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tsung-Yu Tsai Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 翁孟慈 無
- 翁昭旼 無
- Huey-Ling Chen 無
- YEN-HSUAN NI 無
- 吳嘉峯 無
- 謝銘鈞 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 王彥博 無
- Tsung-Chieh Yang 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 許振銘 無
- Chia-Jung Kuo 無
- Puo-Hsien Le 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- FAN -FENG CHIANG 無
- 陳家昌 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
Severely Active Crohn’s Disease
Objectives
Primary:
To compare the efficacy of brazikumab with that of placebo to achieve CDAI remission at Week 12
Secondary:
To compare the efficacy of brazikumab with that of placebo to achieve endoscopic response, CDAI response, and clinical remission at Week 12
Test Drug
Brazikumab (AMG 139)
Active Ingredient
Brazikumab
Dosage Form
Solution for infusion
Dosage
720
Endpoints
Primary:
CDAI remission at Week 12:
CDAI score < 150
Secondary:
Key Secondary: Endoscopic response at
Week 12:
Minimum of 50% decrease from
Baseline in SES-CD total score
Clinical remission 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
CDAI response at Week 12:
CDAI score of < 150 points or
CDAI reduction from Baseline of
≥ 100 points
CDAI remission at Week 12:
CDAI score < 150
Secondary:
Key Secondary: Endoscopic response at
Week 12:
Minimum of 50% decrease from
Baseline in SES-CD total score
Clinical remission 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
CDAI response at Week 12:
CDAI score of < 150 points or
CDAI reduction from Baseline of
≥ 100 points
Inclution Criteria
Age
1 At the time of signing the ICF, the participant must be 18 to 80 years of age, inclusive.
Type of Participant and Disease Characteristics
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, defined by a CDAI score of 220 to 450 points AND
(3a and 3b must be met):
(a) CDAI LSF and AP scores will be obtained during Screening on an eDiary. The total
CDAI score will be calculated at Screening Visit 2 and will include data from the last
7 days. Within the 7 consecutive day period, participants are to have at least 4 days of
evening diary entries. This calculation will be used to determine CDAI LSF and AP
eligibility and allow for scheduling of the ileocolonoscopy.
The following criteria must also be met:
i. Average daily CDAI LSF score ≥ 5
OR
ii. Average daily CDAI AP score ≥ 2
(b) Evidence of active intestinal mucosal inflammation, as demonstrated on video-recorded
ileocolonoscopy performed during the Screening Period prior to first dose of study
intervention and scored by a blinded central reader with agreement on the following
findings:
i. SES-CD score of at least 6. A narrowing that cannot be passed is exclusionary
(please refer to Exclusion Criterion #9). The SES-CD score is to be calculated
based on segments that can be evaluated by the endoscopist.
OR
ii. For isolated ileal disease, SES-CD score of greater than 4.
All efforts are to be made to complete the ileocolonoscopy no less than 5 business days prior
to randomization to allow for the evaluation of the endoscopic subscore by the central
reader.
Note: CDAI and PRO scores for eligibility must be met before endoscopy is performed.
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. To fulfill this criterion,
the participant must meet at least 1 of the following:
(a) Had an inadequate response to 1 of these agents, ie, defined as persistent signs and/or
symptoms of active CD judged by the investigator’s overall clinical assessment of the
participant’s history taking into consideration a lack of clinical improvement or inability
to maintain previously achieved clinical improvement despite treatment with
medication(s) used according to the local label and generally considered to be safe and
effective in treating CD.
(b) Was intolerant to 1 of these agents, defined as the inability to continue treatment due to
adverse effects, regardless of treatment dose.
(c) Has CS dependence, defined as the daily or regularly scheduled use of CS to manage
CD signs/symptoms and inability to discontinue CS use without the prompt return of
CD signs/symptoms.
5 Where applicable, participants taking any of the following medications must be at a stable
dose as defined:
(a) 5-aminosalicylates must be at a stable dose for 2 weeks prior to Screening
ileocolonoscopy.
(b) Oral prednisone (or equivalent) up to 25 mg/day or equivalent, must be at a stable dose
for 2 weeks prior to the Screening ileocolonoscopy and kept stable until the Week 12
assessment. Please see Section 6.6.2 for additional details for CS.
(c) Budesonide up to 9 mg/day, must be at a stable dose for 2 weeks prior to Screening
ileocolonoscopy and kept stable until the Week 12 assessment. Please see Section 6.6.2
for additional details for CS.
(d) Oral antibiotics for the treatment of CD must be at a stable dose for at least 2 weeks
prior to Screening ileocolonoscopy. This criterion does not apply to antibiotics used for
the treatment of active infection.
(e) Immunomodulators (specifically azathioprine, 6-mercaptopurine, and methotrexate):
participant must have been on treatment for a minimum of 8 weeks and must be kept at stable doses (except for cases of toxicity when the dose may be lowered) for 4 weeks
prior to Randomization (Day 1).
(f) Probiotics (eg, Culturelle® and Saccharomyces boulardii) must be at a stable dose at
Randomization (Day 1).
6 Participant must have the QFT-TB test performed and meet the following TB criteria. A TB
worksheet must also be completed (see Appendix G):
(a) Participant has no known history of active TB.
(b) Participant has no known history of latent TB without completion of an appropriate
course of intervention.
(c) Meets 1 of the following acceptable TB test results:
i. Negative QFT-TB obtained from central laboratory during Screening, OR
ii. For a positive QFT-TB test obtained during Screening from the central laboratory,
active TB must be ruled out. If the QFT-TB test is positive due to latent TB, there
must be documentation that a full course of prophylaxis for latent TB was
completed, and there is no evidence of active TB on chest x-ray within 8 weeks
prior to SV1 or during Screening. Participants with a new diagnosis of latent TB
during Screening will be excluded.
OR
iii. Indeterminate QFT-TB test (confirmed as indeterminate on retest during Screening)
obtained during the Screening Period from the central laboratory with ongoing
QFT-TB testing as outlined in Appendix G. Participants with an indeterminate
QFT-TB test can continue with Screening if they have all of the following:
1 no symptoms/risk factors per TB worksheet provided by the sponsor
2 no known recent exposure to a case of active TB
3 no evidence of active TB on chest x-ray within 8 weeks prior to Screening or
during Screening.
(d) 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.
Reproduction
Contraceptive use by men or women should be consistent with local regulations regarding the
methods of contraception for those participating in clinical studies.
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; cessation or
continuation of contraception after this point is to be discussed with a responsible physician
in accordance with local regulations and guidelines. Highly effective methods (those that
can achieve a failure rate of less than 1% per year when used consistently and correctly)
include:
o Combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation- oral, intravaginal, or transdermal
o Progestogen-only hormonal contraception associated with inhibition of ovulationoral, injectable, or implantable
o Intrauterine device
o Intrauterine hormone-releasing system
o Bilateral tubal occlusion
o Sexual abstinence, ie, refraining from heterosexual intercourse (The reliability of
sexual abstinence needs to be evaluated in relation to the duration of the clinical
study and the preferred and usual lifestyle of the participant)
o Vasectomized sexual partner, provided that partner is the sole sexual partner of the
WOCBP study participant and that the vasectomized partner has received medical
assessment of the surgical success
8 Women not of childbearing potential are defined as women who are either permanently
sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), 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. The following age-specific requirements apply:
o Women < 50 years old would be considered postmenopausal if they have been
amenorrhoeic for 12 months or more following cessation of exogenous hormonal
treatment and FSH levels in the postmenopausal range. Until FSH is documented to
be within menopausal range, treat the participant as having childbearing potential.
o Women ≥ 50 years old would be considered postmenopausal if they have been
amenorrhoeic for 12 months or more following cessation of all exogenous
hormonal treatment.
If these criteria are not met, the participant should be regarded as having childbearing
potential.
9 Nonsterilized males who are sexually active with a female partner of childbearing potential
should use condoms during treatment and until the end of relevant systemic exposure in the
male participant, plus a further 18 weeks. For a female partner of childbearing potential,
contraception recommendations should also be considered (as described in Inclusion
Criterion 7).
Informed Consent
10 Capable of giving signed informed consent as described in Appendix A, which includes
compliance with the requirements and restrictions listed in the ICF and in this 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.
12 Provision of signed and dated written Optional Genetic Research Information informed
consent prior to collection of samples for optional genetic research that supports Genomic
Initiative.
NOTE: All participants will be asked to participate in this genetic research. Participation is
voluntary and if a participant declines to participate there will be no penalty or loss of
benefit. The participant will not be excluded from any aspect of the main study.
1 At the time of signing the ICF, the participant must be 18 to 80 years of age, inclusive.
Type of Participant and Disease Characteristics
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, defined by a CDAI score of 220 to 450 points AND
(3a and 3b must be met):
(a) CDAI LSF and AP scores will be obtained during Screening on an eDiary. The total
CDAI score will be calculated at Screening Visit 2 and will include data from the last
7 days. Within the 7 consecutive day period, participants are to have at least 4 days of
evening diary entries. This calculation will be used to determine CDAI LSF and AP
eligibility and allow for scheduling of the ileocolonoscopy.
The following criteria must also be met:
i. Average daily CDAI LSF score ≥ 5
OR
ii. Average daily CDAI AP score ≥ 2
(b) Evidence of active intestinal mucosal inflammation, as demonstrated on video-recorded
ileocolonoscopy performed during the Screening Period prior to first dose of study
intervention and scored by a blinded central reader with agreement on the following
findings:
i. SES-CD score of at least 6. A narrowing that cannot be passed is exclusionary
(please refer to Exclusion Criterion #9). The SES-CD score is to be calculated
based on segments that can be evaluated by the endoscopist.
OR
ii. For isolated ileal disease, SES-CD score of greater than 4.
All efforts are to be made to complete the ileocolonoscopy no less than 5 business days prior
to randomization to allow for the evaluation of the endoscopic subscore by the central
reader.
Note: CDAI and PRO scores for eligibility must be met before endoscopy is performed.
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. To fulfill this criterion,
the participant must meet at least 1 of the following:
(a) Had an inadequate response to 1 of these agents, ie, defined as persistent signs and/or
symptoms of active CD judged by the investigator’s overall clinical assessment of the
participant’s history taking into consideration a lack of clinical improvement or inability
to maintain previously achieved clinical improvement despite treatment with
medication(s) used according to the local label and generally considered to be safe and
effective in treating CD.
(b) Was intolerant to 1 of these agents, defined as the inability to continue treatment due to
adverse effects, regardless of treatment dose.
(c) Has CS dependence, defined as the daily or regularly scheduled use of CS to manage
CD signs/symptoms and inability to discontinue CS use without the prompt return of
CD signs/symptoms.
5 Where applicable, participants taking any of the following medications must be at a stable
dose as defined:
(a) 5-aminosalicylates must be at a stable dose for 2 weeks prior to Screening
ileocolonoscopy.
(b) Oral prednisone (or equivalent) up to 25 mg/day or equivalent, must be at a stable dose
for 2 weeks prior to the Screening ileocolonoscopy and kept stable until the Week 12
assessment. Please see Section 6.6.2 for additional details for CS.
(c) Budesonide up to 9 mg/day, must be at a stable dose for 2 weeks prior to Screening
ileocolonoscopy and kept stable until the Week 12 assessment. Please see Section 6.6.2
for additional details for CS.
(d) Oral antibiotics for the treatment of CD must be at a stable dose for at least 2 weeks
prior to Screening ileocolonoscopy. This criterion does not apply to antibiotics used for
the treatment of active infection.
(e) Immunomodulators (specifically azathioprine, 6-mercaptopurine, and methotrexate):
participant must have been on treatment for a minimum of 8 weeks and must be kept at stable doses (except for cases of toxicity when the dose may be lowered) for 4 weeks
prior to Randomization (Day 1).
(f) Probiotics (eg, Culturelle® and Saccharomyces boulardii) must be at a stable dose at
Randomization (Day 1).
6 Participant must have the QFT-TB test performed and meet the following TB criteria. A TB
worksheet must also be completed (see Appendix G):
(a) Participant has no known history of active TB.
(b) Participant has no known history of latent TB without completion of an appropriate
course of intervention.
(c) Meets 1 of the following acceptable TB test results:
i. Negative QFT-TB obtained from central laboratory during Screening, OR
ii. For a positive QFT-TB test obtained during Screening from the central laboratory,
active TB must be ruled out. If the QFT-TB test is positive due to latent TB, there
must be documentation that a full course of prophylaxis for latent TB was
completed, and there is no evidence of active TB on chest x-ray within 8 weeks
prior to SV1 or during Screening. Participants with a new diagnosis of latent TB
during Screening will be excluded.
OR
iii. Indeterminate QFT-TB test (confirmed as indeterminate on retest during Screening)
obtained during the Screening Period from the central laboratory with ongoing
QFT-TB testing as outlined in Appendix G. Participants with an indeterminate
QFT-TB test can continue with Screening if they have all of the following:
1 no symptoms/risk factors per TB worksheet provided by the sponsor
2 no known recent exposure to a case of active TB
3 no evidence of active TB on chest x-ray within 8 weeks prior to Screening or
during Screening.
(d) 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.
Reproduction
Contraceptive use by men or women should be consistent with local regulations regarding the
methods of contraception for those participating in clinical studies.
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; cessation or
continuation of contraception after this point is to be discussed with a responsible physician
in accordance with local regulations and guidelines. Highly effective methods (those that
can achieve a failure rate of less than 1% per year when used consistently and correctly)
include:
o Combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation- oral, intravaginal, or transdermal
o Progestogen-only hormonal contraception associated with inhibition of ovulationoral, injectable, or implantable
o Intrauterine device
o Intrauterine hormone-releasing system
o Bilateral tubal occlusion
o Sexual abstinence, ie, refraining from heterosexual intercourse (The reliability of
sexual abstinence needs to be evaluated in relation to the duration of the clinical
study and the preferred and usual lifestyle of the participant)
o Vasectomized sexual partner, provided that partner is the sole sexual partner of the
WOCBP study participant and that the vasectomized partner has received medical
assessment of the surgical success
8 Women not of childbearing potential are defined as women who are either permanently
sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), 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. The following age-specific requirements apply:
o Women < 50 years old would be considered postmenopausal if they have been
amenorrhoeic for 12 months or more following cessation of exogenous hormonal
treatment and FSH levels in the postmenopausal range. Until FSH is documented to
be within menopausal range, treat the participant as having childbearing potential.
o Women ≥ 50 years old would be considered postmenopausal if they have been
amenorrhoeic for 12 months or more following cessation of all exogenous
hormonal treatment.
If these criteria are not met, the participant should be regarded as having childbearing
potential.
9 Nonsterilized males who are sexually active with a female partner of childbearing potential
should use condoms during treatment and until the end of relevant systemic exposure in the
male participant, plus a further 18 weeks. For a female partner of childbearing potential,
contraception recommendations should also be considered (as described in Inclusion
Criterion 7).
Informed Consent
10 Capable of giving signed informed consent as described in Appendix A, which includes
compliance with the requirements and restrictions listed in the ICF and in this 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.
12 Provision of signed and dated written Optional Genetic Research Information informed
consent prior to collection of samples for optional genetic research that supports Genomic
Initiative.
NOTE: All participants will be asked to participate in this genetic research. Participation is
voluntary and if a participant declines to participate there will be no penalty or loss of
benefit. The participant will not be excluded from any aspect of the main study.
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:
(a) Evidence of a recent (within 6 months of Randomization [Day 1]) 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
antiviral treatment) within 4 weeks of Screening
(c) Cytomegalovirus or Epstein-Barr virus infection that has not resolved within 8 weeks
prior to Screening
(d) Clinically significant chronic infection (eg, osteomyelitis) that has not resolved within
8 weeks of Screening
(e) Nonserious infection requiring oral anti-infectives within 2 weeks prior to
randomization must be further discussed with the Study Physician/designee. 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 and there is no anticipation for
surgery.
(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
(i) Clinically significant active infection or signs/symptoms of infection that has the
potential to worsen with immunosuppressive therapy
(j) Signs or symptoms of ongoing infection due to intestinal pathogens
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: (1) positive for hepatitis B surface antigen (HBsAg+) or (2) 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 Prior history of or current diagnosis of a demyelinating disorder.
15 Participant has received the following treatment:
(a) Adalimumab, certolizumab pegol, infliximab, or golimumab: within 8 weeks prior to
Randomization (Day 1)
(b) Vedolizumab or ustekinumab within 12 weeks prior to Randomization (Day 1)
(c) Other prohibited medication, biologic or small molecule treatment within 5 half-lives
prior to Randomization (Day 1)
(d) Fecal microbiota transplantation: within 8 weeks prior to Screening ileocolonoscopy
16 Except for ustekinumab, prior exposure to any biologic agent targeting IL-12 or IL-23 (eg,
risankizumab, briakinumab, mirikizumab, guselkumab, tildrakizumab, or brazikumab).
17 Participants who received cyclosporine, mycophenolate mofetil, sirolimus (rapamycin),
thalidomide, tacrolimus (FK-506), or tofacitinib within 2 weeks prior to Screening Visit 1.
18 Known history of allergy to the study intervention formulation or any of its excipients or
components of the delivery device, or to any other biologic therapy.
19 Participants received more than 1 dose of IV or intramuscular steroids within 2 weeks prior
to Screening Visit 1.
20 Participant received topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal)
steroids within 2 weeks prior to Randomization (Day 1).
21 Participant received a Bacille Calmette-Guérin vaccination within 12 months of
Randomization (Day 1) or any other live vaccine less than 4 weeks prior to Randomization
(Day 1) or is planning to receive any such vaccine over the course of the study.
22 Participant has known or suspected history of chronic use of NSAIDs (defined as at least
3 times per week for more than 3 months; not applicable to daily aspirin use up to 325 mg
per day) and/or opiates, drug, or alcohol abuse. Participants who use marijuana for medicinal
purposes, including treatment of symptoms associated with CD and improving quality of
life, will be permitted in the study. Marijuana use is to be documented as a concomitant
medication. Participants who abuse marijuana (ie, interferes with aspects of the participant’s
life) as judged by the investigator are excluded.
23 History of cancer with the following exceptions:
(a) A history of basal cell carcinoma and/or squamous cell carcinoma of the skin, with
apparent successful curative therapy greater than 12 months prior to Screening, would
not be exclusionary
(b) Carcinoma in situ of the cervix, with apparent successful curative therapy, greater than
12 months prior to Screening.
If there is evidence of intestinal epithelial dysplasia on endoscopy, and confirmed on biopsy,
the participant must be excluded.
24 Clinically significant cardiovascular conditions including recent myocardial infarction,
unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring
hospitalization, or Class III/IV heart failure within 6 months of Screening.
25 Prolonged QTcF interval (QTc > 450 msec or QTC > 480 for participants with bundle
branch block; determined on central ECG), or conditions leading to additional risk for QT
prolongation (eg, congenital long-QT syndrome). Participants with electrolyte abnormalities
such as hypokalemia and hypomagnesemia that would increase the risk of QT prolongation
are to be corrected prior to randomization; the ECG for these participants may be repeated
after electrolyte correction for determination of eligibility if needed.
26 Clinically significant kidney disease including but not limited to:
(a) Acute kidney injury within 6 weeks of Screening. Corrected pre-renal azotemia with
serum creatinine at the participant’s Baseline value during Screening would not be
excluded.
(b) Chronic kidney disease with an estimated glomerular filtration rate of less than
30 ml/min calculated by MDRD equation, as applicable, by the central laboratory at
Screening are excluded.
27 Abnormal laboratory results at Screening:
(a) Liver tests: either AST, ALT, or alkaline phosphatase > 2.0 × ULN or total
bilirubin > 1.5 × ULN (except for participants with Gilbert Syndrome, pathological
evidence of conjugated [direct] hyperbilirubinemia per investigator and/or sponsor
discretion is exclusionary)
(b) Neutrophil count < 1×103
/μL (or < 1.0 GI/L)
(c) Hemoglobin < 8 g/dL
(d) Platelet count < 100 × 103
/μL (or < 100 GI/L)
(e) Evidence of acute or chronic hepatitis B or C infection on central laboratory serology
(see exclusion criterion 12)
(f) Positive central laboratory result for HIV
(g) C. difficile-positive stool testing (antigen and toxin) by central laboratory. For
indeterminate results (antigen positive and toxin negative), a positive C. difficile stool
PCR is exclusionary.
(h) Participant has any other abnormal laboratory results at Screening, which, in the opinion
of the investigator, will prevent the participant from completing the study or will
interfere with the interpretation of the study results.
28 Other concurrent medical conditions: Participant has known, preexisting, clinically
significant endocrine, autoimmune, metabolic, neurologic, renal, gastrointestinal, hepatic, hematological, respiratory or any other system abnormalities that are not associated with CD
and are uncontrolled with standard treatment. Any clinically significant abnormal findings in
physical examination, vital signs, laboratory, or endoscopic assessments during Screening
Period, which in the opinion of the investigator may put the participant at risk because of
his/her participation in the study; may influence the results of the study; compromise the
ability of the participant to give written informed consent, and/or to complete the entire
duration of the study.
29 Participant is currently enrolled in another investigational device or drug study, or is within
35 days or 5 half-lives, whichever is longer, since ending another investigational device or
drug study, or receiving other investigational agent(s), with the exception of “registry” or
“cohort” trials, which may include periodic biological sampling and/or participant
questionnaires but in which no other unlicensed investigational product is administered. In
the event that a participant has received an investigational agent, the elimination half-life of
which is not known, then the last dose must have been received at least 6 months prior to
Randomization (Day 1).
30 Transfusion of blood, plasma, or platelets within the 30 days prior to Screening.
31 Females who are pregnant, nursing, or planning a pregnancy during the study OR females
who are of childbearing potential and do not agree to use a highly effective method of
contraception consistently and correctly.
32 Employees of the clinical study site or any other individuals involved with the conduct of
the study, or immediate family members of such individuals.
33 Previous randomization in the present study
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:
(a) Evidence of a recent (within 6 months of Randomization [Day 1]) 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
antiviral treatment) within 4 weeks of Screening
(c) Cytomegalovirus or Epstein-Barr virus infection that has not resolved within 8 weeks
prior to Screening
(d) Clinically significant chronic infection (eg, osteomyelitis) that has not resolved within
8 weeks of Screening
(e) Nonserious infection requiring oral anti-infectives within 2 weeks prior to
randomization must be further discussed with the Study Physician/designee. 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 and there is no anticipation for
surgery.
(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
(i) Clinically significant active infection or signs/symptoms of infection that has the
potential to worsen with immunosuppressive therapy
(j) Signs or symptoms of ongoing infection due to intestinal pathogens
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: (1) positive for hepatitis B surface antigen (HBsAg+) or (2) 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 Prior history of or current diagnosis of a demyelinating disorder.
15 Participant has received the following treatment:
(a) Adalimumab, certolizumab pegol, infliximab, or golimumab: within 8 weeks prior to
Randomization (Day 1)
(b) Vedolizumab or ustekinumab within 12 weeks prior to Randomization (Day 1)
(c) Other prohibited medication, biologic or small molecule treatment within 5 half-lives
prior to Randomization (Day 1)
(d) Fecal microbiota transplantation: within 8 weeks prior to Screening ileocolonoscopy
16 Except for ustekinumab, prior exposure to any biologic agent targeting IL-12 or IL-23 (eg,
risankizumab, briakinumab, mirikizumab, guselkumab, tildrakizumab, or brazikumab).
17 Participants who received cyclosporine, mycophenolate mofetil, sirolimus (rapamycin),
thalidomide, tacrolimus (FK-506), or tofacitinib within 2 weeks prior to Screening Visit 1.
18 Known history of allergy to the study intervention formulation or any of its excipients or
components of the delivery device, or to any other biologic therapy.
19 Participants received more than 1 dose of IV or intramuscular steroids within 2 weeks prior
to Screening Visit 1.
20 Participant received topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal)
steroids within 2 weeks prior to Randomization (Day 1).
21 Participant received a Bacille Calmette-Guérin vaccination within 12 months of
Randomization (Day 1) or any other live vaccine less than 4 weeks prior to Randomization
(Day 1) or is planning to receive any such vaccine over the course of the study.
22 Participant has known or suspected history of chronic use of NSAIDs (defined as at least
3 times per week for more than 3 months; not applicable to daily aspirin use up to 325 mg
per day) and/or opiates, drug, or alcohol abuse. Participants who use marijuana for medicinal
purposes, including treatment of symptoms associated with CD and improving quality of
life, will be permitted in the study. Marijuana use is to be documented as a concomitant
medication. Participants who abuse marijuana (ie, interferes with aspects of the participant’s
life) as judged by the investigator are excluded.
23 History of cancer with the following exceptions:
(a) A history of basal cell carcinoma and/or squamous cell carcinoma of the skin, with
apparent successful curative therapy greater than 12 months prior to Screening, would
not be exclusionary
(b) Carcinoma in situ of the cervix, with apparent successful curative therapy, greater than
12 months prior to Screening.
If there is evidence of intestinal epithelial dysplasia on endoscopy, and confirmed on biopsy,
the participant must be excluded.
24 Clinically significant cardiovascular conditions including recent myocardial infarction,
unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring
hospitalization, or Class III/IV heart failure within 6 months of Screening.
25 Prolonged QTcF interval (QTc > 450 msec or QTC > 480 for participants with bundle
branch block; determined on central ECG), or conditions leading to additional risk for QT
prolongation (eg, congenital long-QT syndrome). Participants with electrolyte abnormalities
such as hypokalemia and hypomagnesemia that would increase the risk of QT prolongation
are to be corrected prior to randomization; the ECG for these participants may be repeated
after electrolyte correction for determination of eligibility if needed.
26 Clinically significant kidney disease including but not limited to:
(a) Acute kidney injury within 6 weeks of Screening. Corrected pre-renal azotemia with
serum creatinine at the participant’s Baseline value during Screening would not be
excluded.
(b) Chronic kidney disease with an estimated glomerular filtration rate of less than
30 ml/min calculated by MDRD equation, as applicable, by the central laboratory at
Screening are excluded.
27 Abnormal laboratory results at Screening:
(a) Liver tests: either AST, ALT, or alkaline phosphatase > 2.0 × ULN or total
bilirubin > 1.5 × ULN (except for participants with Gilbert Syndrome, pathological
evidence of conjugated [direct] hyperbilirubinemia per investigator and/or sponsor
discretion is exclusionary)
(b) Neutrophil count < 1×103
/μL (or < 1.0 GI/L)
(c) Hemoglobin < 8 g/dL
(d) Platelet count < 100 × 103
/μL (or < 100 GI/L)
(e) Evidence of acute or chronic hepatitis B or C infection on central laboratory serology
(see exclusion criterion 12)
(f) Positive central laboratory result for HIV
(g) C. difficile-positive stool testing (antigen and toxin) by central laboratory. For
indeterminate results (antigen positive and toxin negative), a positive C. difficile stool
PCR is exclusionary.
(h) Participant has any other abnormal laboratory results at Screening, which, in the opinion
of the investigator, will prevent the participant from completing the study or will
interfere with the interpretation of the study results.
28 Other concurrent medical conditions: Participant has known, preexisting, clinically
significant endocrine, autoimmune, metabolic, neurologic, renal, gastrointestinal, hepatic, hematological, respiratory or any other system abnormalities that are not associated with CD
and are uncontrolled with standard treatment. Any clinically significant abnormal findings in
physical examination, vital signs, laboratory, or endoscopic assessments during Screening
Period, which in the opinion of the investigator may put the participant at risk because of
his/her participation in the study; may influence the results of the study; compromise the
ability of the participant to give written informed consent, and/or to complete the entire
duration of the study.
29 Participant is currently enrolled in another investigational device or drug study, or is within
35 days or 5 half-lives, whichever is longer, since ending another investigational device or
drug study, or receiving other investigational agent(s), with the exception of “registry” or
“cohort” trials, which may include periodic biological sampling and/or participant
questionnaires but in which no other unlicensed investigational product is administered. In
the event that a participant has received an investigational agent, the elimination half-life of
which is not known, then the last dose must have been received at least 6 months prior to
Randomization (Day 1).
30 Transfusion of blood, plasma, or platelets within the 30 days prior to Screening.
31 Females who are pregnant, nursing, or planning a pregnancy during the study OR females
who are of childbearing potential and do not agree to use a highly effective method of
contraception consistently and correctly.
32 Employees of the clinical study site or any other individuals involved with the conduct of
the study, or immediate family members of such individuals.
33 Previous randomization in the present study
The Estimated Number of Participants
-
Taiwan
8 participants
-
Global
1140 participants
