Clinical trial NCT03616821: Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis
Official 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ulcerative Colitis
IBD
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-08-06
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Global, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study
Primary purpose: TREATMENT

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


Eligibility 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 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

Primary outcomes:
measure: Percentage of participants with clinical remission
timeFrame: at Week 10
Secondary outcomes:
measure: Percentage of participants with sustained clinical remission
timeFrame: at both Week 10 and Week 54
measure: Percentage of participants with CS-free clinical remission
timeFrame: at Week 54 for patients who are CS-free for at least the last 12 weeks before the assessment at Week 54
measure: Percentage of participants with clinical response
timeFrame: at Week 10
measure: Percentage of participants with endoscopic improvement
timeFrame: at Week 10
measure: Serum concentration of brazikumab
timeFrame: through Week 68
measure: For each dose level: LS mean of Mayo score and brazikumab pre-dose blood concentration
timeFrame: at 12 weeks after dosing
measure: Incidence of anti-drug antibodies
timeFrame: through week 68
measure: Number and percentage of participants with adverse events
timeFrame: through Week 68
measure: Percentage of participants with potentially clinically significant changes in laboratory values
timeFrame: through Week 68
measure: Percentage of participants with potentially clinically significant changes in vital signs
timeFrame: through Week 68
measure: Clinically relevant abnormal findings at physical exam
timeFrame: through Week 68
measure: Percentage of participants with potentially clinically significant changes in ECGs
timeFrame: through Week 68
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Chula Vista
country: United States
facility: Research Site
state: California
city: Lancaster
country: United States
facility: Research Site
state: California
city: Lincoln
country: United States
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state: California
city: Mission Hills
country: United States
facility: Research Site
state: California
city: Poway
country: United States
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state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Clearwater
country: United States
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state: Florida
city: Inverness
country: United States
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state: Florida
city: Kissimmee
country: United States
facility: Research Site
state: Florida
city: Lakeland
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
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state: Florida
city: Miami
country: United States
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state: Florida
city: Naples
country: United States
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state: Florida
city: New Port Richey
country: United States
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state: Florida
city: Tampa
country: United States
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state: Florida
city: Tampa
country: United States
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state: Florida
city: Atlanta
country: United States
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state: Georgia
city: Gurnee
country: United States
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state: Illinois
city: Oak Lawn
country: United States
facility: Research Site
state: Illinois
city: Brownsburg
country: United States
facility: Research Site
state: Indiana
city: Evansville
country: United States
facility: Research Site
state: Indiana
city: Shawnee Mission
country: United States
facility: Research Site
state: Kansas
city: Topeka
country: United States
facility: Research Site
state: Kansas
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Marrero
country: United States
facility: Research Site
state: Louisiana
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Wyoming
country: United States
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state: Michigan
city: Biloxi
country: United States
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state: Mississippi
city: Las Vegas
country: United States
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state: Nevada
city: Las Vegas
country: United States
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state: Nevada
city: New York
country: United States
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state: New York
city: Sunnyside
country: United States
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state: New York
city: Morehead City
country: United States
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state: North Carolina
city: Beachwood
country: United States
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state: Ohio
city: Springfield
country: United States
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state: Ohio
city: Oklahoma City
country: United States
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state: Oklahoma
city: Uniontown
country: United States
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state: Pennsylvania
city: Amarillo
country: United States
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state: Texas
city: Carrollton
country: United States
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state: Texas
city: Houston
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state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
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state: Texas
city: Humble
country: United States
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state: Texas
city: Pflugerville
country: United States
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: North Chesterfield
country: United States
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state: Virginia
city: Chicoutimi
country: Canada
facility: Research Site
state: Quebec
city: Brno
country: Czechia
facility: Research Site
city: Ceske Budejovice
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Bangalore
country: India
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city: Hyderabad
country: India
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city: Jaipur
country: India
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city: New Delhi
country: India
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city: Rajkot
country: India
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city: Surat
country: India
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city: Haifa
country: Israel
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city: Jerusalem
country: Israel
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city: Petah Tikva
country: Israel
facility: Research Site
city: Milano
country: Italy
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city: Negrar
country: Italy
facility: Research Site
city: Rho
country: Italy
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city: Roma
country: Italy
facility: Research Site
city: Asahikawa-shi
country: Japan
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Fukuyama-shi
country: Japan
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city: Hakodate-shi
country: Japan
facility: Research Site
city: Kasama-shi
country: Japan
facility: Research Site
city: Kashiwa-shi
country: Japan
facility: Research Site
city: Koshigaya-shi
country: Japan
facility: Research Site
city: Kure-shi
country: Japan
facility: Research Site
city: Minato-ku
country: Japan
facility: Research Site
city: Nagaoka-shi
country: Japan
facility: Research Site
city: Onga-gun
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Takarazuka-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Wonju-si
country: Korea, Republic of
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Chojnice
country: Poland
facility: Research Site
city: Częstochowa
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Ksawerów
country: Poland
facility: Research Site
city: Piaseczno
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Rzeszow
country: Poland
facility: Research Site
city: Sopot
country: Poland
facility: Research Site
city: Toruń
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: San Juan
country: Puerto Rico
facility: Research Site
city: Aramil
country: Russian Federation
facility: Research Site
city: Izhevsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Tomsk
country: Russian Federation
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Bloemfontein
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Plumstead
country: South Africa
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: West Bromwich
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Kathy Bohannon
role: STUDY_DIRECTOR
References: