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

Crohn's Disease Clinical Trial

— INTREPID  

Official 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03759288
• Other study ID #: D5271C00001
• Secondary ID: #3150-301-008201
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: December 7, 2018
• Est. completion date: October 18, 2023

Study information

• Verified date: October 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study seeks to evaluate the safety and efficacy of brazikumab versus placebo (Stage I) and versus an active comparator (Stage 2) in participants with moderately to severely active CD and will include assessments of clinical response as demonstrated by improvement of symptoms and colonic mucosal appearance as observed on endoscopy

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 89
• Est. completion date: October 18, 2023
• Est. primary completion date: October 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 peritonitis or receiving treatment for peritonitis within 8 weeks prior to Screening • Participant has any underlying condition that predisposes participant to infections • Clinically significant active infection or signs/symptoms of infection that has the potential to worsen with immunosuppressive therapy • 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.

13. Known history of primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, includingHIV infection.

14. Prior history of or current diagnosis of a demyelinating disorder.

15. Participant has received the following treatment: • Adalimumab, certolizumab pegol, infliximab, or golimumab: within 8 weeks prior to Randomization • Vedolizumab or ustekinumab within 12 weeks prior to Randomization • Other prohibited medication, biologic or small molecule treatment within 5 half-lives prior to Randomization • 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.

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.

21. Participant received a Bacille Calmette-Guérin vaccination within 12 months of Randomization or any other live vaccine less than 4 weeks prior to Randomization 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 325mg per day) and/or opiates, drug, or alcohol abuse.

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 (b) Carcinoma in situ of the cervix, with apparent successful curative therapy, greater than 12 months prior to Screening.

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).

26. Clinically significant kidney disease

27. Abnormal laboratory results at Screening

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.

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)

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. . Complete exclusion criteria are in the study protocol

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease
• IBD

Intervention

Drug:
• Brazikumab low dose
Intravenous Brazikumab on Days 1, 29, and 57, followed by subcutaneous Brazikumab on Day 85 and every 4 weeks through Week 48
• Brazikumab high dose
Intravenous Brazikumab on Days 1, 29, and 57, followed by subcutaneous Brazikumab on Day 85 and every 4 weeks through Week 48
• Humira®
Administered subcutaneously on Day 1, Day 15, and Day 29 and every 2 weeks through Week 50.
• Placebo
Intravenous placebo on Days 1, 29, 57 followed by subcutaneous placebo on Day 85 and every 4 weeks through Week 48

Locations

Country	Name	City	State
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	New Westminster	British Columbia
Czechia	Research Site	Ceske Budejovice
Czechia	Research Site	Horovice
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Olomouc
Germany	Research Site	Augsburg
Germany	Research Site	Berlin
Germany	Research Site	Hamburg
Germany	Research Site	Kiel
Germany	Research Site	Minden
Germany	Research Site	Remscheid
Germany	Research Site	Ulm
Hungary	Research Site	Budapest
India	Research Site	Bangalore
India	Research Site	Hyderabad
India	Research Site	Jaipur
India	Research Site	Surat
Israel	Research Site	HaIFA
Israel	Research Site	Jerusalem
Israel	Research Site	Petah Tikva
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Padova
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Poland	Research Site	Bydgoszcz
Poland	Research Site	Chojnice
Poland	Research Site	Kraków
Poland	Research Site	Poznan
Poland	Research Site	Rzeszow
Poland	Research Site	Sopot
Poland	Research Site	Torun
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Poland	Research Site	Zamosc
Russian Federation	Research Site	Aramil
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Perm
Slovakia	Research Site	Banska Bystrica
Slovakia	Research Site	Kosice
Slovakia	Research Site	Nitra
South Africa	Research Site	Cape Town
South Africa	Research Site	Cape Town
South Africa	Research Site	Johannesburg
South Africa	Research Site	Plumstead
Spain	Research Site	Madrid
Spain	Research Site	Pontevedra
Spain	Research Site	Valencia
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
United Kingdom	Research Site	Coventry
United Kingdom	Research Site	West Bromwich
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Atlanta	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Beachwood	Ohio
United States	Research Site	Boca Raton	Florida
United States	Research Site	Brownsburg	Indiana
United States	Research Site	Carrollton	Texas
United States	Research Site	Chesterfield	Michigan
United States	Research Site	Clearwater	Florida
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Decatur	Georgia
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Kissimmee	Florida
United States	Research Site	Lakeland	Florida
United States	Research Site	Lancaster	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lincoln	California
United States	Research Site	Little Rock	Arkansas
United States	Research Site	McAllen	Texas
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Morehead City	North Carolina
United States	Research Site	Naples	Florida
United States	Research Site	North Chesterfield	Virginia
United States	Research Site	Oak Lawn	Illinois
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Pflugerville	Texas
United States	Research Site	Phoenix	Arizona
United States	Research Site	Poway	California
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	San Diego	California
United States	Research Site	Spokane	Washington
United States	Research Site	Stafford	Texas
United States	Research Site	Tampa	Florida
United States	Research Site	Uniontown	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Slovakia,  South Africa,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage 1. Percentage of patients with CDAI remission	CDAI remission is defined as achieving the CDAI score below 150 (measured by PRO questionnaire and objective items (i.e. weight, hematocrit)).	at Week 12
Primary	Stage 2. Percentage of patients with endoscopic response	Endoscopic response is described as minimum of 50% decrease from Baseline in SES-CD total score.	at Week 52
Primary	Stage 2. Percentage of patients with clinical remission	Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: 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 (measured by PRO questionnaire).	at Week 52
Secondary	Stage 1. Percentage of patients with endoscopic response	Endoscopic response is described as minimum of 50% decrease from Baseline in SES-CD total score.	at Week 12
Secondary	Stage 1. Percentage of patients with clinical remission	Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: 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 (measured by PRO questionnaire).	at Week 12
Secondary	Stage 1. Percentage of patients with CDAI response	CDAI response is defined as achieving the CDAI score of < 150 points or CDAI reduction from Baseline of = 100 points (measured by PRO questionnaire and objective items (i.e. weight, hematocrit)).	at Week 12
Secondary	Stage 1. Percentage of patients with CDAI remission	CDAI remission is defined as achieving the CDAI score below 150 (measured by PRO questionnaire and objective items (i.e. weight, hematocrit)).	at both Week 12 and Week 52
Secondary	Stage 1. Percentage of patients with CDAI response	CDAI response is defined as achieving the CDAI score of < 150 points or CDAI reduction from Baseline of = 100 points (measured by PRO questionnaire and objective items (i.e. weight, hematocrit)).	at both Week 12 and Week 52
Secondary	Stage 1. Percentage of patients with endoscopic response	Endoscopic response is described as minimum of 50% decrease from Baseline in SES-CD total score.	at both Week 12 and Week 52
Secondary	Stage 1. Percentage of patients with clinical remission	Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: 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 (measured by PRO questionnaire).	at both Week 12 and Week 52
Secondary	Stage 1. Percentage of patients with endoscopic remission	Endoscopic remission is defined as achieving the 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	at Week 52
Secondary	Stage 1. Percentage of patients with clinical remission	Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: 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 (measured by PRO questionnaire).	at Week 52
Secondary	Stage 1. Percentage of patients with CDAI response	CDAI response is defined as achieving the CDAI score of < 150 points or CDAI reduction from Baseline of = 100 points (measured by PRO questionnaire and objective items (i.e. weight, hematocrit)).	at Week 52
Secondary	Stage 1. Percentage of patients with CDAI remission	CDAI remission is defined as achieving the CDAI score below 150 (measured by PRO questionnaire and objective items (i.e. weight, hematocrit)).	at Week 52
Secondary	Stage 1. Percentage of patients with endoscopic response	Endoscopic response is described as minimum of 50% decrease from Baseline in SES-CD total score.	at Week 52
Secondary	Stage 1. Percentage of patients with SES-CD total score of 0-2	SES-CD total score of 0-2	at Week 52
Secondary	Stage 1. Percentage of patients with endoscopic response and endoscopic remission	Endoscopic response: Minimum of 50% decrease from Baseline in SES-CD total score Endoscopic remission: 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	Endoscopic response at Week 12, endoscopic remission at Week 52
Secondary	Stage 1. Serum concentration of brazikumab	Pharmacokinetics: concentration of brazikumab in serum	Through Week 68
Secondary	Stage 1. Incidence of anti-drug antibodies	Immunogenicity: incidence of brazikumab anti-drug antibodies in serum	Through Week 68
Secondary	Stage 1. Exposure-response	Derive exposure response model linking primary endpoint to metrics of model predicted individual brazikumab exposures	Through Week 68
Secondary	Stage 1. Serum IL-22 concentration clinical cutoff for Stage 2	Derive the relationship between baseline serum IL-22 concentration and efficacy of brazikumab through CDAI remission and endoscopic response	at Week 12
Secondary	Stage 1. Number and percentage of patients with adverse events	Number and percentage of patients with reported adverse events.	Through Week 68
Secondary	Stage 1. Percentage of patients with potentially clinically significant changes in laboratory values	Percentage of patients with clinically significant changes in hematology, clinical chemistry, urinalysis.	Through Week 68
Secondary	Stage 1. Percentage of patients with potentially clinically significant changes in vital signs	Percentage of patients with potentially clinically significant changes in systolic, diastolic pulse rate.	Through Week 68
Secondary	Stage 1. Percentage of patients with potentially clinically significant changes in physical exams	Percentage of patients with potentially clinically significant changes in full physical exams.	Through Week 68
Secondary	Stage 1. Percentage of patients with potentially clinically significant changes in ECGs	Percentage of patients with potentially clinically significant changes in 12-lead ECG recordings	Through Week 68
Secondary	Stage 2. Percentage of patients with endoscopic response	Endoscopic response is described as minimum of 50% decrease from Baseline in SES-CD total score	at both Week 12 and Week 52
Secondary	Stage 2. Percentage of patients with clinical remission	Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: 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 (measured by PRO questrionare)	at both Week 12 and Week 52
Secondary	Stage 2: Percentage of patients with endoscopic remission	Endoscopic remission: - 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	at Week 52
Secondary	Stage 2. Percentage of patients with clinical remission	Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: 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 (measured by PRO questrionare)	at Week 52
Secondary	Stage 2: Percentage of patients with CS-free endoscopic remission	Percentage of patients achieving Endoscopic remission and are CS-free where endoscopic remission is defined as : - 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	at Week 52
Secondary	Stage 2. Percentage of patients with CS-free clinical remission	Percentage of patients achieving CS-free 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	at Week 52
Secondary	Stage 2: Percentage of patients with CS-free endoscopic remission	For participants taking CS at Baseline, percentage of patients achieving CS-free endoscopic remission	at Week 52
Secondary	Stage 2: Percentage of patients with CS-free clinical remission	For participants taking CS at Baseline, percentage of patients achieving CS-free clinical remission	at Week 52
Secondary	Stage 2. Percentage of patients with endoscopic response	Endoscopic response is described as minimum of 50% decrease from Baseline in SES-CD total score	at Week 12
Secondary	Stage 2. Percentage of patients with clinical remission	Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: 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 (measured by PRO questrionare)	at Week 12
Secondary	Stage 2. Percentage of patients with endoscopic response and endoscopic remission	Endoscopic response is defined as minimum of 50% decrease from Baseline in SES-CD total score Endoscopic remission: - 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	Endoscopic response at Week 12, endoscopic remission at Week 52
Secondary	Stage 2. Percentage of patients with clinical remission	Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: 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 (measured by PRO questionnaire)	at both Week 12 and Week 52
Secondary	Stage 2. Percentage of patients achieving CS-free endoscopic response	Endoscopic response is described as minimum of 50% decrease from Baseline in SES-CD total score	at Week 52
Secondary	Stage 2. Percentage of patients with clinical remission	Percentage of patients achieving CS-free clinical remission Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: 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.(measured by PRO questionnaire)	at Week 52
Secondary	Stage 2. Serum concentration of brazikumab	Pharmacokinetics: concentration of brazikumab in serum	Through Week 68
Secondary	Stage 2. Incidence of anti-drug antibodies	Immunogenicity: incidence of brazikumab anti-drug antibodies in blood serum	Through Week 68
Secondary	Stage 2. Exposure-response	Derive exposure response model linking primary endpoint to metrics of model predicted individual brazikumab exposures	Through Week 68
Secondary	Stage 2. Number and percentage of patients with adverse events	Number and percentage of patients with reported adverse events	Through Week 68
Secondary	Stage 2. Percentage of patients with potentially clinically significant changes in laboratory values	Percentage of patients with clinically significant changes in hematology, clinical chemistry, urinalysis.	Through Week 68
Secondary	Stage 2. Percentage of patients with potentially clinically significant changes in vital signs	Percentage of patients with potentially clinically significant changes in systolic, diastolic pulse rate	Through Week 68
Secondary	Stage 2. Percentage of patients with potentially clinically significant changes in physical exams	Percentage of patients with potentially clinically significant changes in full physical exams	Through Week 68
Secondary	Stage 2. Percentage of patients with potentially clinically significant changes in ECGs	Percentage of patients with potentially clinically significant changes in 12-lead ECG recordings	Through Week 68