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

• Register: EUCTR
• Last refreshed on: 8 January 2024
• Main ID: EUCTR2018-004346-42-ES
• Date of registration: 11/11/2019
• Prospective Registration: Yes
• Primary sponsor: Allergan Ltd.
• Public title: An Active and Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Crohn's Disease
• Scientific title: A 52-Week, Multicenter, Randomized, Double-blind, Double-dummy, 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 - 52-Week Phase 2b/3 Crohn’s Disease Study
• Date of first enrolment: 26/12/2019
• Target sample size: 2000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004346-42
• 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, Operationally Seamless If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Ukraine, United Kingdom, United States

Contacts

• Name: CTRG
• Affiliation: Allergan Ltd.

• Name: CTRG
• Affiliation: Allergan Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Aged 16 to 80 years, inclusive, or minimum age of adult consent according to local regulations, at Screening. For participants less than 18 years of age, the participant must weigh at least 40 kg at Screening.
2. 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
4. Participant had an inadequate response or intolerance to intervention with oral aminosalicylates, oral CS, azathioprine, methotrexate, or 6-mercaptopurine, or demonstrated CS dependence for the treatment of CD.
5. Participants taking 5-aminosalicylates, Oral prednisone (or equivalent), Budesonide, Immunomodulators, Oral antibiotics, Probiotics must be at a stable dose.
6. Meets the following TB criteria: Participant has no known history of active TB; Participant has no known history of latent TB without completion of an appropriate course of intervention or is presently taking appropriate ongoing prophylactic intervention; Meets 1 of the following acceptable TB test results: Negative QFT-TB obtained from central laboratory within 4 weeks prior to randomization or For a positive QFT-TB test obtained during Screening from the central laboratory, active TB must be ruled out or Indeterminate QFT-TB test obtained during the Screening period from the central laboratory with ongoing QFT-TB testing; A negative tuberculin skin test is required if the QFT-TB test is not approved/registered in that country; Participants with a history of using anti-TNFa agents for a treatment course of 1 year or longer who have discontinued an anti-TNFa 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.
7. Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 acceptable methods of contraception from Screening.
8. Female participants who are post-menopausal and of non-childbearing potential must have an elevated FSH at or above the range for post-menopausal women by the central laboratory during Screening.
9. Nonsterilized males who are sexually active with a female partner of childbearing potential must comply with the methods of contraception
10. Ability to provide written informed consent prior to any study procedures
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
Are the trial subjects under 18? yes
Number of subjects for this age range: 150
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 600

Exclusion criteria:
1. Participant has previously received Humira® and was intolerant to treatment or had met the criteria for primary or secondary non-response to treatment:
a. Primary non-response: Signs and symptoms of persistently active disease despite a history of at least 1 induction regimen of Humira® per the local label consisting of at least 2 doses at least 2 weeks apart
b. Secondary non-response: Recurrence of symptoms of persistently active disease during scheduled maintenance dosing of Humira® per the local label following prior clinical benefit
c. Intolerance: AE associated with discontinuation of Humira® therapy, including, but not limited to, hypersensitivity, infusion-related reaction, infection, or congestive heart failure
2. Participant is unable or unwilling to have endoscopic procedures performed during the study.
3. History or current diagnosis of ulcerative colitis, indeterminate colitis, microscopic colitis, ischemic colitis, colonic mucosal dysplasia, primary sclerosing cholangitis, or untreated bile acid malabsorption.
4. History of toxic megacolon within 3 months prior to Baseline (Visit 2).
5. Any intra-abdominal surgery, bowel resection, diversion, placement of ostomy or stoma within 3 months prior to Screening. Participants with a draining stoma are excluded.
6. Participant has an enterocutaneous or entovesicular fistula. Participants with active fistulas may be considered if there is no anticipation for surgery and there is no evidence of active infection (eg, abscess) after further discussion with the study medical monitor.
7. Bowel perforation during the 6 months prior to Screening or evidence of obstruction within 3 months of Screening.
8. 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.
9. 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).
10. Ongoing nutritional dependency for total parenteral nutrition or an elemental diet at Screening.
11. Participant has any of the following related to infections:
a. Evidence of a recent (within 6 months of Baseline [Visit 2]) 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 anti-viral treatment) within 4 weeks of Screening
c. Cytomegalovirus or Epstein-Barr virus infection that has not completely resolved within 8 weeks prior to Screening
d. Clinically significant chronic infection (eg, osteomyelitis) that has not resolved within 8 weeks of Screening
e. Non-serious infection requiring oral anti-infectives within 2 weeks prior to randomization must be further discussed with the study medical monitor. 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 periana

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

Health Condition(s) or Problem(s) studied

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

Crohn's Disease
MedDRA version: 20.0 Level: LLT Classification code 10011402 Term: Crohn's disease (colon) System Organ Class: 100000004856

Intervention(s)

Product Name: Brazikumab
Product Code: Anti-Interleukin-23 Immunoglobulin G2 (IgG2) Human
Pharmaceutical Form: Solution for injection/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, AGN-151-598
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Intravenous use

Trade Name: Humira®
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Brazikumab
Product Code: Anti-Interleukin-23 Immunoglobulin G2 (IgG2) Human
Pharmaceutical Form: Solution for injection/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: 120-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: Stage 1: To compare the efficacy of brazikumab with that of placebo to achieve endoscopic response and clinical remission at Week 12

Stage 2: To compare the efficacy of brazikumab with that of Humira® to achieve endoscopic response and clinical remission at Week 52 in participants who are BM+

Primary end point(s): Stage 1:
a.Endoscopic response
b.Clinical remission
Stage 2:
a.Endoscopic response
b.Clinical remission

Secondary Objective: Stage 1:
To compare the efficacy of brazikumab with that of placebo to achieve sustained endoscopic response and clinical remission at both Wk12 and Wk52
To compare the efficacy of brazikumab with that of placebo to achieve endoscopic remission and clinical remission at Wk52
To compare the efficacy of brazikumab with that of placebo to achieve endoscopic response at Week 12 and endoscopic remission at Wk52 and clinical remission at both Wk12 and Wk52
Stage 2:
To compare the efficacy of brazikumab with that of Humira® to achieve sustained endoscopic response and clinical remission at both Wk12 and Wk52 in participants who are BM+
To compare the efficacy of brazikumab with that of Humira® to achieve endoscopic remission and clinical remission at Wk52 in participants who are BM+
To compare the efficacy of brazikumab with that of Humira® to achieve CS free (for the last 12 wks before the assessment at Wk 52) endoscopic and clinical remission at Wk 52 in participants who are BM+

Timepoint(s) of evaluation of this end point: Stage 1:
a.at Week 12: Minimum of 50% decrease from Baseline in SES-CD total score
b.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
Stage 2:
a.at Week 52
b.at Week 52

Secondary Outcome(s)

Secondary end point(s): Stage 1:
a. Endoscopic response
b. Clinical remission
c. Endoscopic remission
d. Clinical remission
e. Endoscopic response and endoscopic remission
f. Clinical remission
Stage 2:
a. Endoscopic response
b. Clinical remission
c. Endoscopic remission
d. Clinical remission
e. CS-free endoscopic remission
f. CS-free clinical remission

Timepoint(s) of evaluation of this end point: Stage 1:
a. at both Week 12 and Week 52
b. at both Week 12 and Week 52
c. at Week 52
- 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
d. at Week 52
e. at Week 12 and at Week 52
f. at both Week 12 and Week 52
Stage 2:
a. at both Week 12 and Week 52.
b. at both Week 12 and Week 52
c. at Week 52
d. at Week 52
e. at Week 52
f. at Week 52

Secondary ID(s)

111,773

NCT03759288

2018-004346-42-GB

3150-301-008

Source(s) of Monetary Support

Allergan Sales LLC

Ethics review

Status: Approved
Approval date: 28/11/2019
Contact: