Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis (Expedition)

A 54-Week, Multicenter, Randomized, Double-blind, Placebo Controlled, Parallel-group Phase 2 Study to Assess the Efficacy and Safety of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis (Expedition Lead-in)

The present study (D5272C00001/Legacy #3151-201-008) aims to evaluate the efficacy and safety of brazikumab in patients with moderately to severely active UC and will include assessments of clinical responses as demonstrated by improvement of symptoms and of colonic mucosal appearance as observed on endoscopy

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis; IBD
• Intervention / Treatment: Drug: Brazikumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • Research Site
• Czechia
  • Brno, Czechia, 636 00
    • Research Site
  • Hradec Králové, Czechia, 500 12
    • Research Site
  • Ostrava, Czechia, 702 00
    • Research Site
  • České Budějovice, Czechia, 370 01
    • Research Site
• Germany
  • Hamburg, Germany, 20251
    • Research Site
  • Kiel, Germany, 24105
    • Research Site
  • Ulm, Germany, 89081
    • Research Site
• Hungary
  • Debrecen, Hungary, 4032
    • Research Site
• India
  • Bangalore, India, 560054
    • Research Site
  • Hyderabad, India, 500032
    • Research Site
  • Jaipur, India, 302001
    • Research Site
  • New Delhi, India, 110075
    • Research Site
  • Rajkot, India, 360004
    • Research Site
  • Surat, India, 395002
    • Research Site
• Israel
  • Haifa, Israel, 31096
    • Research Site
  • Jerusalem, Israel, 9103102
    • Research Site
  • Petah Tikva, Israel, 4941492
    • Research Site
• Italy
  • Milan, Italy, 20132
    • Research Site
  • Negrar, Italy, 37024
    • Research Site
  • Rho, Italy, 20017
    • Research Site
  • Roma, Italy, 00168
    • Research Site
• Japan
  • Asahikawa-shi, Japan, 070-8610
    • Research Site
  • Chiba, Japan, 260-8677
    • Research Site
  • Fukuoka, Japan, 810-8563
    • Research Site
  • Fukuyama-shi, Japan
    • Research Site
  • Hakodate-shi, Japan, 040-8585
    • Research Site
  • Kasama-shi, Japan, 309-1793
    • Research Site
  • Kashiwa-shi, Japan, 277-0871
    • Research Site
  • Koshigaya-shi, Japan, 343-8555
    • Research Site
  • Kure-shi, Japan, 737-0023
    • Research Site
  • Minatoku, Japan, 108-8642
    • Research Site
  • Nagaoka-shi, Japan, 940-2085
    • Research Site
  • Onga-gun, Japan, 807-0051
    • Research Site
  • Sapporo, Japan, 064-0919
    • Research Site
  • Takarazuka-shi, Japan, 665-0827
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-079
    • Research Site
  • Chojnice, Poland, 89-600
    • Research Site
  • Częstochowa, Poland, 42-202
    • Research Site
  • Gdansk, Poland, 80-382
    • Research Site
  • Krakow, Poland, 31-513
    • Research Site
  • Ksawerów, Poland, 95-054
    • Research Site
  • Piaseczno, Poland, 05-500
    • Research Site
  • Poznan, Poland, 60-702
    • Research Site
  • Rzeszów, Poland, 35-302
    • Research Site
  • Sopot, Poland, 81-756
    • Research Site
  • Torun, Poland, 87-100
    • Research Site
  • Warsaw, Poland, 00-189
    • Research Site
  • Warsaw, Poland, 03-580
    • Research Site
  • Wroclaw, Poland, 52-210
    • Research Site
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Research Site
• Russia
  • Aramil, Russia, 624002
    • Research Site
  • Izhevsk, Russia, 426035
    • Research Site
  • Moscow, Russia, 115419
    • Research Site
  • Novosibirsk, Russia, 630007
    • Research Site
  • Perm, Russia, 614000
    • Research Site
  • Tomsk, Russia, 634050
    • Research Site
• Slovakia
  • Košice, Slovakia, 04013
    • Research Site
• South Africa
  • Bloemfontein, South Africa, 9301
    • Research Site
  • Cape Town, South Africa, 7500
    • Research Site
  • Cape Town, South Africa, 7708
    • Research Site
  • Plumstead, South Africa, 7800
    • Research Site
• South Korea
  • Busan, South Korea, 48108
    • Research Site
  • Daegu, South Korea, 42415
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
  • Seoul, South Korea, 06973
    • Research Site
  • Wŏnju, South Korea, 26426
    • Research Site
• Spain
  • Valencia, Spain, 46010
    • Research Site
• Taiwan
  • Taichung, Taiwan, 40447
    • Research Site
  • Taipei, Taiwan, 100
    • Research Site
• Ukraine
  • Kyiv, Ukraine, 03680
    • Research Site
  • Vinnytsia, Ukraine, 21009
    • Research Site
• United Kingdom
  • West Bromwich, United Kingdom, B71 4HJ
    • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85037
      • Research Site
    • Tucson, Arizona, United States, 85712
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72212
      • Research Site
  • California
    • Chula Vista, California, United States, 91911
      • Research Site
    • Lancaster, California, United States, 93534
      • Research Site
    • Lincoln, California, United States, 95648
      • Research Site
    • Mission Hills, California, United States, 91345
      • Research Site
    • Poway, California, United States, 92064
      • Research Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Research Site
  • Florida
    • Clearwater, Florida, United States, 33756
      • Research Site
    • Inverness, Florida, United States, 34452
      • Research Site
    • Kissimmee, Florida, United States, 34741
      • Research Site
    • Lakeland, Florida, United States, 33813
      • Research Site
    • Miami, Florida, United States, 33165
      • Research Site
    • Miami, Florida, United States, 33157
      • Research Site
    • Miami Lakes, Florida, United States, 33016
      • Research Site
    • Naples, Florida, United States, 34102
      • Research Site
    • New Port Richey, Florida, United States, 34653
      • Research Site
    • Tampa, Florida, United States, 33614
      • Research Site
    • Tampa, Florida, United States, 33626
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Research Site
  • Illinois
    • Gurnee, Illinois, United States, 60031
      • Research Site
    • Oak Lawn, Illinois, United States, 60453
      • Research Site
  • Indiana
    • Brownsburg, Indiana, United States, 46112
      • Research Site
    • Evansville, Indiana, United States, 47715
      • Research Site
  • Kansas
    • Shawnee Mission, Kansas, United States, 66226
      • Research Site
    • Topeka, Kansas, United States, 66606
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Research Site
    • Marrero, Louisiana, United States, 70072
      • Research Site
    • Shreveport, Louisiana, United States, 71105
      • Research Site
  • Michigan
    • Wyoming, Michigan, United States, 49519
      • Research Site
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Research Site
    • Las Vegas, Nevada, United States, 89123
      • Research Site
  • New York
    • New York, New York, United States, 10016
      • Research Site
    • Sunnyside, New York, United States, 11104
      • Research Site
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Research Site
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Research Site
    • Springfield, Ohio, United States, 45503
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Research Site
  • Pennsylvania
    • Uniontown, Pennsylvania, United States, 15401
      • Research Site
  • Texas
    • Amarillo, Texas, United States, 79109
      • Research Site
    • Carrollton, Texas, United States, 75007
      • Research Site
    • Houston, Texas, United States, 77058
      • Research Site
    • Houston, Texas, United States, 77017
      • Research Site
    • Houston, Texas, United States, 77598
      • Research Site
    • Humble, Texas, United States, 77346
      • Research Site
    • Pflugerville, Texas, United States, 78660
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
    • San Antonio, Texas, United States, 78258
      • Research Site
  • Virginia
    • North Chesterfield, Virginia, United States, 23236
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ability to provide informed consent
2. Aged 18 to 80 years of age
3. Diagnosis of UC with an onset of symptoms for a minimum of 3 months prior to Screening
4. Evidence of UC extending proximal to the rectum (≥ 15 cm of involved colon)

5. Moderately to severely active UC as defined by:

   1. Average daily mMS Stool Frequency subscore ≥ 1 AND Average daily mMS Rectal Bleeding subscore ≥ 1
   2. Modified Mayo endoscopic subscore of ≥ 2 based on a full colonoscopy within 14 days prior to randomization.
6. Participant had an inadequate response or intolerance to intervention with conventional treatment or prior biological treatment or demonstrated CS dependence for the treatment of UC. 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.
7. Participants taking 5-aminosalicylates, oral prednisone (or equivalent), oral budesonide, or immunomodulators must be at a stable dose or discontinued. Topical (rectal) aminosalicylic acid or topical (rectal) steroids should be discontinued.
8. 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 throughout the study and for at least 18 weeks after the last dose of study intervention.
9. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal.
10. Non sterilized 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.
11. No known history of active TB or latent TB without completion of appropriate intervention and negative QFT-TB during Screening.

Complete inclusion criteria are in the Clinical Study Protocol

Exclusion Criteria:

1. Participant has UC limited to the rectum (ie, not beyond 15 cm of the anal verge).
2. Current diagnosis of fulminant colitis, a diagnosis of CD or indeterminate colitis, presence or history of a fistula consistent with CD, primary sclerosing cholangitis, celiac disease, or untreated bile acid malabsorption. Participants with a history of toxic megacolon within 12 months of screening are excluded.
3. History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, ileostomy, or other prior colonic resection, or need for surgical intervention for control of UC anticipated within 6 months.

4. Participant has received the following treatment:

   1. Infliximab: within 8 weeks prior to randomization.
   2. Adalimumab, certolizumab pegol, or golimumab: within 8 weeks prior to randomization.
   3. Vedolizumab or ustekinumab within 12 weeks of randomization.
   4. Other prohibited medication, biologic or small molecule treatment within 5 half-lives prior to randomization.
   5. Fecal microbiota transplantation: within 8 weeks prior to randomization.
5. Criterion deleted as part of Amendment 5 v6.0
6. Except for ustekinumab, prior exposure to any biologic agent targeting IL-12 or IL-23.
7. 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.
8. Participant received cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, tacrolimus (FK-506), or tofacitinib within 2 weeks prior to Screening.
9. Participants who received IV or intramuscular steroids within 2 weeks prior to Screening.
10. 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(s), or receiving other investigational agent(s).
11. Participant received a transfusion of blood, plasma, or platelets within 30 days prior to Screening.
12. Participant received a Bacille Calmette-Guérin vaccination within 12 months of randomization or any other live vaccine less than 4 weeks prior to randomization.

13. Participant has any of the following criteria related to infections:

    1. Evidence of a recent systemic fungal infection, requiring inpatient hospitalization, and/or antifungal treatment.
    2. Any infection requiring hospitalization or treatment with IV anti-infectives within 4 weeks of Screening.
    3. Cytomegalovirus or Epstein-Barr virus infection that has not resolved within 8 weeks prior to Screening.
    4. Clinically significant chronic infection that has not resolved within 8 weeks of Screening.
    5. Nonserious infection requiring oral anti-infectives within 2 weeks prior to randomization must be further discussed with study medical monitor.
    6. Clinical evidence of or suspected to have an abscess during Screening.
    7. Any underlying condition that predisposes the participant to infections.
    8. Participant had previous allogenic bone marrow transplant or history of organ or cell-based transplantation.
    9. Clinically significant active infection or signs/symptoms of infection that has the potential to worsen with immunosuppressive therapy.
    10. Signs or symptoms of ongoing infection due to intestinal pathogens.
14. Participant has known or suspected history of chronic use of NSAIDs and/or opiates, drug, or alcohol abuse.
15. History of cancer with the following exceptions: history of basal cell carcinoma and/or squamous cell carcinoma of the skin OR carcinoma in situ of the cervix; with apparent successful curative therapy, greater than 12 months prior to Screening.
16. Clinically significant cardiovascular conditions.
17. Prolonged QTcF interval or conditions leading to additional risk for QT prolongation.
18. Clinically significant kidney disease
19. Abnormal laboratory results at Screening as defined in the study protocol
20. Participant is pregnant or breastfeeding or plans to become pregnant during the study.
21. Participant has other known, pre-existing, clinically significant medical conditions that are not associated with UC and are uncontrolled with standard treatment.
22. Participant has any disorder that may compromise the ability of the participant to give written informed consent and/or to comply with all required study procedures.
23. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals.

Complete exclusion criteria are in the Clinical Study Protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brazikumab Dose 1; Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through week 50	Drug: Brazikumab; Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through Week 50
Experimental: Brazikumab Dose 2; Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through Week 50	Drug: Brazikumab; Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through Week 50
Placebo Comparator: Placebo; Intravenous placebo on day 1, day 15, and day 43 followed by Subcutaneous every 4 weeks beginning on day 71 through Week 50.	Drug: Placebo; Intravenous placebo on day 1, day 15, and day 43 followed by Subcutaneous placebo every 4 weeks beginning on Day 71 through Week 50.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Remission	Efficacy was assessed using the Mayo Scoring System for assessment of Ulcerative Colitis. The Mayo score assesses; stool frequency,; rectal bleeding,; endoscopic findings, and; physician's assessment of disease activity. Each of these four subscores can be scored as 0, 1, 2, or 3, where 0 is a normal finding and 3 corresponds to severe disease. The Mayo score has been modified (modified Mayo Score, mMS) to specify no friability in the endoscopy subscore of 1 (mild disease). Clinical Remission is defined by the mMS at Week 10: Endoscopy subscore = 0 or 1, AND; Rectal bleeding subscore = 0, AND; Stool frequency subscore = 0 or 1, AND at least a 1-point decrease from baseline Further, if the patient; discontinue treatment prematurely for any reason; takes rescue treatment or meet the rescue criteria; uses prohibited medication the patient is considered as unsuccessfully treated and imputed as non-responder	at Week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Clinical Remission	Sustained clinical remission defined as Modified Mayo Score (mMS): Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore = 0 or 1 AND at least a 1 point decrease from baseline Further, if the patient; discontinue treatment prematurely for any reason; takes rescue treatment or meet the rescue criteria; uses prohibited medication the patient is considered as unsuccessfully treated and imputed as non-responder	Week 10 and 54
CS-free Clinical Remission	CS-free clinical remission defined as mMS: Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore = 0 or 1 AND at least a 1 point decrease from baseline Further, if the patient; discontinue treatment prematurely for any reason; takes rescue treatment or meet the rescue criteria; uses prohibited medication the patient is considered as unsuccessfully treated and imputed as non-responder	Week 54
Clinical Response	Efficacy was assessed using the Mayo Scoring System for assessment of Ulcerative Colitis. The Mayo score assesses; stool frequency,; rectal bleeding,; endoscopic findings, and; physician's assessment of disease activity. Each of these four subscores can be scored as 0, 1, 2, or 3, where 0 is a normal finding and 3 corresponds to severe disease. The Mayo score is the sum of the four subscores. The Mayo score has been modified (modified Mayo Score, mMS) to specify no friability in the endoscopy subscore of 1 (mild disease). Clinical response is defined as Reduction in mMS ≥ 2 points from baseline AND ≥ 30% from baseline AND a decrease in the rectal bleeding score ≥ 1 point from baseline or a score of 0 or 1 Further, if the patient; discontinue treatment prematurely for any reason; takes rescue treatment or meet the rescue criteria; uses prohibited medication the patient is considered as unsuccessfully treated and imputed as non-responder	Week 10
Endoscopic Improvement	Efficacy was assessed using the Mayo Scoring System for assessment of Ulcerative Colitis. The Mayo score assesses; stool frequency,; rectal bleeding,; endoscopic findings, and; physician's assessment of disease activity. Each of these four subscores can be scored as 0, 1, 2, or 3, where 0 is a normal finding and 3 corresponds to severe disease. Endoscopic improvement is defined as Endoscopy subscore ≤ 1. Further, if the patient; discontinue treatment prematurely for any reason; takes rescue treatment or meet the rescue criteria; uses prohibited medication the patient is considered as unsuccessfully treated and imputed as non-responder	Week 10
Serum Concentrations of Brazikumab (Induction)	Pharmacokinetics: concentration of brazikumab in serum	through week 10
Exposure-response	Participants with Clinical Remission by Quartile of Brazikumab concentration	through week 68
Incidence of Anti-drug Antibodies (Induction)	Immunogenicity: incidence of brazikumab anti-drug antibodies in serum	through week 10
Adverse Events	Number and percentage of patients with reported adverse events.	Through week 68: Induction: AE with onset on or after first IV dose up to SC dose, or early term trt date + 18 wks after last dose. Maintenance: AE with onset on or after first SC dose up to and including 18 weeks after date of last SC dose.
Laboratory Values	Percentage of patients with potentially clinically significant changes in hematology, clinical chemistry, urinalysis.	through week 68
Vital Signs	Percentage of patients with potentially clinically significant changes in systolic and diastolic blood pressure, and pulse rate.	through week 68
Abnormal ECG Results Through Week 68	Percentage of patients with potentially clinically significant changes in 12-lead ECG recordings	through week 68
Serum Concentrations of Brazikumab (Maintenance)	Pharmacokinetics: concentration of brazikumab in serum	Week 30 through week 68
Incidence of Anti-drug Antibodies (Maintenance)	Immunogenicity: incidence of brazikumab anti-drug antibodies in serum	Week 30 through week 68
mMS Total Score (Induction)	mMS total score at baseline and Week 10	through Week 10
mMS Component Score: Endoscopy (Induction)	Number of participants in each score category for Endoscopy score	through Week 10
mMS Component Score: Stool Frequency (Induction)	Number of participants in each score category for Stool frequency	through Week 10
mMS Component Score: Rectal Bleeding (Induction)	Number of participants in each score category for Rectal bleeding	through Week 10
Total mMS (Maintenance)	mMS total score at baseline and Week 54	Week 54
mMS Component Score: Endoscopy (Maintenance)	Number of participants in each score category for Endoscopy score	through Week 54
mMS Component Score: Stool Frequency (Maintenance)	Number of participants in each score category for Stool frequency score	through Week 54
mMS Component Score: Rectal Bleeding (Maintenance)	Number of participants in each score category for Rectal bleeding score	through Week 54

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Examination	Physical examination as safety assessment, to facilitate the evaluation of the safety objective (Adverse Events).	through week 68

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Kathy Bohannon, AstraZeneca

Publications and helpful links

Helpful Links

• CRS Synopsis
• SAP
• CSP

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2018
• Primary Completion (Actual): October 23, 2023
• Study Completion (Actual): October 23, 2023

Study Registration Dates

• First Submitted: August 1, 2018
• First Submitted That Met QC Criteria: August 1, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: D5272C00001; 2018-001605-93 (EudraCT Number); Legacy #3151-201-008 (Other Identifier: Allergan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes