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

• Register: ClinicalTrials.gov
• Last refreshed on: 20 November 2023
• Main ID: NCT03616821
• Date of registration: 01/08/2018
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis Expedition
• Scientific title: 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)
• Date of first enrolment: August 7, 2018
• Target sample size: 242
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT03616821
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

Australia, Austria, Belgium, Bulgaria, Canada, Czechia, France, Germany, Hungary, India, Israel, Italy, Japan, 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 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 stan


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

Health Condition(s) or Problem(s) studied

Ulcerative Colitis

IBD

Intervention(s)

Drug: Placebo

Drug: Brazikumab

Primary Outcome(s)

Percentage of participants with clinical remission [Time Frame: at Week 10]

Secondary Outcome(s)

For each dose level: LS mean of Mayo score and brazikumab pre-dose blood concentration [Time Frame: at 12 weeks after dosing]

Percentage of participants with CS-free clinical remission [Time Frame: at Week 54 for patients who are CS-free for at least the last 12 weeks before the assessment at Week 54]

Incidence of anti-drug antibodies [Time Frame: through week 68]

Percentage of participants with sustained clinical remission [Time Frame: at both Week 10 and Week 54]

Clinically relevant abnormal findings at physical exam [Time Frame: through Week 68]

Percentage of participants with potentially clinically significant changes in ECGs [Time Frame: through Week 68]

Percentage of participants with potentially clinically significant changes in vital signs [Time Frame: through Week 68]

Number and percentage of participants with adverse events [Time Frame: through Week 68]

Percentage of participants with clinical response [Time Frame: at Week 10]

Percentage of participants with potentially clinically significant changes in laboratory values [Time Frame: through Week 68]

Serum concentration of brazikumab [Time Frame: through Week 68]

Percentage of participants with endoscopic improvement [Time Frame: at Week 10]

Secondary ID(s)

2018-001605-93

D5272C00001

Legacy #3151-201-008

Source(s) of Monetary Support

Please refer to primary and secondary sponsors