An Active and Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 8 January 2024
• Main ID: EUCTR2018-001605-93-GB
• Date of registration: 04/04/2019
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: An Active and Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis
• Scientific title: A 54-Week Treatment, Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo and Active-Controlled, Parallel-Group Phase 2 Study to Assess the Efficacy and Safety of Brazikumab in Participants with Moderately to Severely Active Ulcerative Colitis - Phase 2 Dose-finding UC Study
• Date of first enrolment: 01/07/2019
• Target sample size: 375
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001605-93
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Double dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czech Republic, Czechia, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Poland, Romania, Russian Federation, Singapore, South Africa, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Information Center
• Affiliation: AstraZeneca

• Name: Information Center
• Affiliation: AstraZeneca

Key inclusion & exclusion criteria

Inclusion criteria:
1. Ability to provide written informed consent prior to any study procedures and willing and able 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.
2. Aged 18 to 80 years of age, inclusive, at screening.
3. Diagnosis of UC 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 infectious causes, and characteristic endoscopic and histologic findings.
4. Evidence of UC extending proximal to the rectum (= 15 cm of involved colon).
5. Moderately to severely active UC as defined by Stool Frequency and Rectal Bleeding subscores and Modified Mayo endoscopic subscore.
6. Participant had an inadequate, failed response, or intolerance to intervention with oral corticosteroids, azathioprine, methotrexate, or 6-mercaptopurine, or demonstrated corticosteroid dependence for the treatment of ulcerative colitis.
7. Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 acceptable methods of contraception.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 325
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1. Participant has UC limited to the rectum (ie, not beyond 15 cm of the anal verge)
2. History of fulminant colitis, a diagnosis of Crohn’s disease or indeterminate colitis, presence or history of a fistula consistent with Crohn’s disease, primary sclerosing cholangitis, celiac disease, or bile acid malabsorption. Participants with a history of toxic megacolon within 12 months of screening.
3. History of subtotal colectomy with ileorectostomy or colectomy with ileonal 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:
- Infliximab: within 8 weeks prior to Baseline (Visit 2)
- Adalimumab, certolizumab pegol, or golimumab: within 10 weeks prior to Baseline (Visit 2)
- Vedolizumab within 18 weeks prior to Baseline (Visit 2)
- Other prohibited medication, biologic or small molecule treatment within 5 half-lives prior to Baseline (Visit 2)
5. Participant has previously received vedolizumab, and was intolerant to intervention or
had met the criteria for primary or secondary non-response to intervention.

19. Participant is pregnant, breastfeeding, or plans to become pregnant during the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Name: Brazikumab
Product Code: Anti-Interleukin-23 Immunoglobulin G2 (IgG2) Human
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: BRAZIKUMAB
CAS Number: 1610353-18-8
Other descriptive name: Anti-Interleukin-23 Immunoglobulin G2 (IgG2) Human Monoclonal Antibody; previously referred to as MEDI2070 and AMG 139
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Entyvio
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Entyvio
CAS Number: 943609-66-3
Other descriptive name: VEDOLIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Powder for concentrate for solution for injection/infusion
Route of administration of the placebo: Intravenous use

Product Name: Brazikumab
Product Code: Anti-Interleukin-23 Immunoglobulin G2 (IgG2) Human
Pharmaceutical Form: Solution for injection
INN or Proposed INN: BRAZIKUMAB
CAS Number: 1610353-18-8
Other descriptive name: Anti-Interleukin-23 Immunoglobulin G2 (IgG2) Human Monoclonal Antibody; previously referred to as MEDI2070 and AMG 139
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: -To compare the efficacy of brazikumab with that of placebo to achieve clinical remission

Secondary Objective: -To compare the efficacy of brazikumab with that of placebo to achieve sustained clinical remission
-To compare the efficacy of brazikumab with that of placebo to achieve corticosteroid-free (CS-free) clinical remission
-To evaluate the pharmacokinetics (PK) and immunogenicity of brazikumab in participants with UC
-To characterize the exposure-response relationships of brazikumab

Timepoint(s) of evaluation of this end point: Mayo score items:
Stool frequency - Visit 1 through Follow-up 2 (e-diary)
Rectal bleeding - Visit 1 through Follow-up 2 (e-diary)
Findings of endoscopy - Visits 1, 6, 17
Physician’s global assessment - Visits 1, 6, 17
Each individual item assessed on 0-3 ordinal scale described in Mayo Scoring System for Assessment of Ulcerative Colitis Activity.

Primary end point(s): Clinical remission:
- modified Mayo Score (mMS) at Week 10:
Endoscopy subscore = 0 or 1, AND
Rectal bleeding subscore = 0, AND
Stool frequency subscore = 0

Secondary Outcome(s)

Secondary end point(s): 1. Sustained clinical remission:
- mMS at both Week 10 and Week 54:
Endoscopy subscore = 0 or 1, AND
Rectal bleeding subscore = 0, AND
Stool frequency subscore = 0
2. CS-free clinical remission:
- mMS at Week 54 for participants who are CS-free for at least the last 12 weeks before the assessment at Week 54:
Endoscopy subscore = 0 or 1, AND
Rectal bleeding subscore = 0, AND
Stool frequency subscore = 0
3. Population PK model of serum concentrations of brazikumab and analysis for serum anti-brazikumab antibodies
4. Exposure-response model linking primary endpoints to metrics of model-predicted individual
brazikumab exposures

Timepoint(s) of evaluation of this end point: as listed above

Secondary ID(s)

IND

3151-201-008

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 01/07/2019
Contact: