An Active and Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Crohn's Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 4 December 2023
• Main ID: NCT03759288
• Date of registration: 20/11/2018
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: An Active and Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Crohn's Disease INTREPID
• Scientific title: 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)
• Date of first enrolment: December 7, 2018
• Target sample size: 89
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT03759288
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2/Phase 3

Countries of recruitment

Australia, Austria, Bulgaria, Canada, China, Czechia, France, Germany, Hungary, India, Israel, Italy, Korea, Republic of, Poland, Puerto Rico, Romania, Russian Federation, Slovakia, South Africa, Spain, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Kathy Bohannon
• Affiliation: AstraZeneca

Key inclusion & exclusion criteria

Inclusion and Exclusion Criteria are the same for both Stage 1 and Stage 2; however,
participants enrolled in Stage 1 will not be permitted to enroll in Stage 2.

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 defined by a CDAI score of 220 to 450 AND; CDAI LSF
score = 5 OR CDAI AP score = 2; AND SES-CD of at least 6

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, Immunomodulators, Probiotics must be at a stable
dose.

6. Participant must have the QFT-TB test performed and meet the following TB criteria.

A TB worksheet must also be completed:

1. Participant has no known history of active TB.

2. Participant has no known history of latent TB without completion of an appropriate
course of intervention.

3. 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 or treated and negative QFT-TB confirmed by central laboratory OR iii. Indeterminate
QFT-TB test 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

4. confirmed QFT-TB negative by central laboratory

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.

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.

Complete inclusion criteria are in the study protocol

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.

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 irrespective of the time from surgery.

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) 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. • Cytomegalovirus or Epstein-Barr virus infection that
has not resolved within 8 weeks prior to Screening • Clinically significant chronic
infection (eg, osteomyelitis) that has not resolved within 8 weeks of Screening •
Nonserious infection requiring oral anti-infectives within 2 weeks prior to
randomization must be further discussed with the Study Physician/designee. •
Participant has clinical evidence of or suspected to have an abscess during Screening.
• Diagnosis of


Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Crohn's Disease

IBD

Intervention(s)

Drug: Brazikumab high dose

Drug: Brazikumab low dose

Drug: Placebo

Drug: Humira®

Primary Outcome(s)

Stage 2. Percentage of patients with clinical remission [Time Frame: at Week 52]

Stage 2. Percentage of patients with endoscopic response [Time Frame: at Week 52]

Stage 1. Percentage of patients with CDAI remission [Time Frame: at Week 12]

Secondary Outcome(s)

Stage 1. Percentage of patients with endoscopic response [Time Frame: at both Week 12 and Week 52]

Stage 1. Percentage of patients with potentially clinically significant changes in ECGs [Time Frame: Through Week 68]

Stage 1. Serum IL-22 concentration clinical cutoff for Stage 2 [Time Frame: at Week 12]

Stage 2. Percentage of patients with endoscopic response [Time Frame: at both Week 12 and Week 52]

Stage 2. Percentage of patients with endoscopic response [Time Frame: at Week 12]

Stage 1. Percentage of patients with CDAI remission [Time Frame: at Week 52]

Stage 1. Percentage of patients with CDAI response [Time Frame: at both Week 12 and Week 52]

Stage 1. Percentage of patients with endoscopic response [Time Frame: at Week 52]

Stage 1. Percentage of patients with potentially clinically significant changes in laboratory values [Time Frame: Through Week 68]

Stage 2. Percentage of patients with potentially clinically significant changes in ECGs [Time Frame: Through Week 68]

Stage 1. Percentage of patients with CDAI remission [Time Frame: at both Week 12 and Week 52]

Stage 1. Percentage of patients with CDAI response [Time Frame: at Week 52]

Stage 2. Exposure-response [Time Frame: Through Week 68]

Stage 2. Percentage of patients with CS-free clinical remission [Time Frame: at Week 52]

Stage 2. Percentage of patients with potentially clinically significant changes in laboratory values [Time Frame: Through Week 68]

Stage 2. Percentage of patients with potentially clinically significant changes in physical exams [Time Frame: Through Week 68]

Stage 1. Number and percentage of patients with adverse events [Time Frame: Through Week 68]

Stage 1. Percentage of patients with endoscopic remission [Time Frame: at Week 52]

Stage 1. Percentage of patients with endoscopic response and endoscopic remission [Time Frame: Endoscopic response at Week 12, endoscopic remission at Week 52]

Stage 1. Percentage of patients with potentially clinically significant changes in vital signs [Time Frame: Through Week 68]

Stage 2. Percentage of patients with clinical remission [Time Frame: at Week 52]

Stage 2: Percentage of patients with CS-free clinical remission [Time Frame: at Week 52]

Stage 1. Percentage of patients with clinical remission [Time Frame: at Week 52]

Stage 2. Incidence of anti-drug antibodies [Time Frame: Through Week 68]

Stage 1. Exposure-response [Time Frame: Through Week 68]

Stage 1. Percentage of patients with clinical remission [Time Frame: at Week 12]

Stage 1. Percentage of patients with CDAI response [Time Frame: at Week 12]

Stage 1. Percentage of patients with clinical remission [Time Frame: at both Week 12 and Week 52]

Stage 1. Incidence of anti-drug antibodies [Time Frame: Through Week 68]

Stage 1. Percentage of patients with SES-CD total score of 0-2 [Time Frame: at Week 52]

Stage 2. Percentage of patients with clinical remission [Time Frame: at both Week 12 and Week 52]

Stage 2. Percentage of patients with clinical remission [Time Frame: at Week 12]

Stage 1. Percentage of patients with endoscopic response [Time Frame: at Week 12]

Stage 1. Percentage of patients with potentially clinically significant changes in physical exams [Time Frame: Through Week 68]

Stage 1. Serum concentration of brazikumab [Time Frame: Through Week 68]

Stage 2. Percentage of patients with potentially clinically significant changes in vital signs [Time Frame: Through Week 68]

Stage 2: Percentage of patients with endoscopic remission [Time Frame: at Week 52]

Stage 2. Number and percentage of patients with adverse events [Time Frame: Through Week 68]

Stage 2. Serum concentration of brazikumab [Time Frame: Through Week 68]

Stage 2. Percentage of patients achieving CS-free endoscopic response [Time Frame: at Week 52]

Stage 2. Percentage of patients with endoscopic response and endoscopic remission [Time Frame: Endoscopic response at Week 12, endoscopic remission at Week 52]

Stage 2: Percentage of patients with CS-free endoscopic remission [Time Frame: at Week 52]

Secondary ID(s)

2018-004346-42

#3150-301-008

D5271C00001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors