Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03616821




Registration number
NCT03616821
Ethics application status
Date submitted
1/08/2018
Date registered
6/08/2018
Date last updated
9/11/2023

Titles & IDs
Public title
Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis
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)
Secondary ID [1] 0 0
Legacy #3151-201-008
Secondary ID [2] 0 0
D5272C00001
Universal Trial Number (UTN)
Trial acronym
Expedition
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 0 0
IBD 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Brazikumab
Treatment: Drugs - Placebo

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

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

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.


Treatment: Drugs: 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

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of participants with clinical remission
Timepoint [1] 0 0
at Week 10
Secondary outcome [1] 0 0
Percentage of participants with sustained clinical remission
Timepoint [1] 0 0
at both Week 10 and Week 54
Secondary outcome [2] 0 0
Percentage of participants with CS-free clinical remission
Timepoint [2] 0 0
at Week 54 for patients who are CS-free for at least the last 12 weeks before the assessment at Week 54
Secondary outcome [3] 0 0
Percentage of participants with clinical response
Timepoint [3] 0 0
at Week 10
Secondary outcome [4] 0 0
Percentage of participants with endoscopic improvement
Timepoint [4] 0 0
at Week 10
Secondary outcome [5] 0 0
Serum concentration of brazikumab
Timepoint [5] 0 0
through Week 68
Secondary outcome [6] 0 0
For each dose level: LS mean of Mayo score and brazikumab pre-dose blood concentration
Timepoint [6] 0 0
at 12 weeks after dosing
Secondary outcome [7] 0 0
Incidence of anti-drug antibodies
Timepoint [7] 0 0
through week 68
Secondary outcome [8] 0 0
Number and percentage of participants with adverse events
Timepoint [8] 0 0
through Week 68
Secondary outcome [9] 0 0
Percentage of participants with potentially clinically significant changes in laboratory values
Timepoint [9] 0 0
through Week 68
Secondary outcome [10] 0 0
Percentage of participants with potentially clinically significant changes in vital signs
Timepoint [10] 0 0
through Week 68
Secondary outcome [11] 0 0
Clinically relevant abnormal findings at physical exam
Timepoint [11] 0 0
through Week 68
Secondary outcome [12] 0 0
Percentage of participants with potentially clinically significant changes in ECGs
Timepoint [12] 0 0
through Week 68

Eligibility
Key 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
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/08/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/10/2023
Sample size
Target
Accrual to date
Final
242
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Mississippi
Country [13] 0 0
United States of America
State/province [13] 0 0
Nevada
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Oklahoma
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Czechia
State/province [22] 0 0
Brno
Country [23] 0 0
Czechia
State/province [23] 0 0
Ceske Budejovice
Country [24] 0 0
Czechia
State/province [24] 0 0
Hradec Kralove
Country [25] 0 0
Czechia
State/province [25] 0 0
Ostrava
Country [26] 0 0
Germany
State/province [26] 0 0
Hamburg
Country [27] 0 0
Germany
State/province [27] 0 0
Kiel
Country [28] 0 0
Germany
State/province [28] 0 0
Ulm
Country [29] 0 0
Hungary
State/province [29] 0 0
Debrecen
Country [30] 0 0
India
State/province [30] 0 0
Bangalore
Country [31] 0 0
India
State/province [31] 0 0
Hyderabad
Country [32] 0 0
India
State/province [32] 0 0
Jaipur
Country [33] 0 0
India
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New Delhi
Country [34] 0 0
India
State/province [34] 0 0
Rajkot
Country [35] 0 0
India
State/province [35] 0 0
Surat
Country [36] 0 0
Israel
State/province [36] 0 0
Haifa
Country [37] 0 0
Israel
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Jerusalem
Country [38] 0 0
Israel
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Petah Tikva
Country [39] 0 0
Italy
State/province [39] 0 0
Milano
Country [40] 0 0
Italy
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Negrar
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Italy
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Rho
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Italy
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Roma
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Japan
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Asahikawa-shi
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Japan
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Chiba-shi
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Japan
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Fukuoka-shi
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Japan
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Fukuyama-shi
Country [47] 0 0
Japan
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Hakodate-shi
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Japan
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Kasama-shi
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Japan
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Kashiwa-shi
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Japan
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Koshigaya-shi
Country [51] 0 0
Japan
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Kure-shi
Country [52] 0 0
Japan
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Minato-ku
Country [53] 0 0
Japan
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Nagaoka-shi
Country [54] 0 0
Japan
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Onga-gun
Country [55] 0 0
Japan
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Sapporo-shi
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Japan
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Takarazuka-shi
Country [57] 0 0
Korea, Republic of
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Busan
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Korea, Republic of
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Daegu
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Korea, Republic of
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Seoul
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Korea, Republic of
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Wonju-si
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Poland
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Bydgoszcz
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Poland
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Chojnice
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Czestochowa
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Gdansk
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Kraków
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Poland
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Ksawerów
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Poland
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Piaseczno
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Poland
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Poznan
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Poland
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Rzeszow
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Poland
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Sopot
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Poland
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Torun
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Poland
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Warszawa
Country [73] 0 0
Poland
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Wroclaw
Country [74] 0 0
Puerto Rico
State/province [74] 0 0
San Juan
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Aramil
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Izhevsk
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Moscow
Country [78] 0 0
Russian Federation
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Novosibirsk
Country [79] 0 0
Russian Federation
State/province [79] 0 0
Perm
Country [80] 0 0
Russian Federation
State/province [80] 0 0
Tomsk
Country [81] 0 0
Slovakia
State/province [81] 0 0
Kosice
Country [82] 0 0
South Africa
State/province [82] 0 0
Bloemfontein
Country [83] 0 0
South Africa
State/province [83] 0 0
Cape Town
Country [84] 0 0
South Africa
State/province [84] 0 0
Plumstead
Country [85] 0 0
Spain
State/province [85] 0 0
Valencia
Country [86] 0 0
Taiwan
State/province [86] 0 0
Taichung
Country [87] 0 0
Taiwan
State/province [87] 0 0
Taipei
Country [88] 0 0
Ukraine
State/province [88] 0 0
Kyiv
Country [89] 0 0
Ukraine
State/province [89] 0 0
Vinnytsia
Country [90] 0 0
United Kingdom
State/province [90] 0 0
West Bromwich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT03616821
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Kathy Bohannon
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03616821