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

Ulcerative Colitis Clinical Trial

— Expedition  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03616821
• Other study ID #: D5272C00001
• Secondary ID: Legacy #3151-201
• Status: Terminated
• Phase: Phase 2
• Start date: August 7, 2018
• Est. completion date: October 23, 2023

Study information

• Verified date: October 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Other known NCT identifiers

• NCT04718818

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 242
• Est. completion date: October 23, 2023
• Est. primary completion date: October 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• IBD
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• 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
• 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.

Locations

Country	Name	City	State
Canada	Research Site	Chicoutimi	Quebec
Czechia	Research Site	Brno
Czechia	Research Site	Ceske Budejovice
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Ostrava
Germany	Research Site	Hamburg
Germany	Research Site	Kiel
Germany	Research Site	Ulm
Hungary	Research Site	Debrecen
India	Research Site	Bangalore
India	Research Site	Hyderabad
India	Research Site	Jaipur
India	Research Site	New Delhi
India	Research Site	Rajkot
India	Research Site	Surat
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Petah Tikva
Italy	Research Site	Milano
Italy	Research Site	Negrar
Italy	Research Site	Rho
Italy	Research Site	Roma
Japan	Research Site	Asahikawa-shi
Japan	Research Site	Chiba-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Fukuyama-shi
Japan	Research Site	Hakodate-shi
Japan	Research Site	Kasama-shi
Japan	Research Site	Kashiwa-shi
Japan	Research Site	Koshigaya-shi
Japan	Research Site	Kure-shi
Japan	Research Site	Minato-ku
Japan	Research Site	Nagaoka-shi
Japan	Research Site	Onga-gun
Japan	Research Site	Sapporo-shi
Japan	Research Site	Takarazuka-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Wonju-si
Poland	Research Site	Bydgoszcz
Poland	Research Site	Chojnice
Poland	Research Site	Czestochowa
Poland	Research Site	Gdansk
Poland	Research Site	Kraków
Poland	Research Site	Ksawerów
Poland	Research Site	Piaseczno
Poland	Research Site	Poznan
Poland	Research Site	Rzeszow
Poland	Research Site	Sopot
Poland	Research Site	Torun
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Puerto Rico	Research Site	San Juan
Russian Federation	Research Site	Aramil
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Tomsk
Slovakia	Research Site	Kosice
South Africa	Research Site	Bloemfontein
South Africa	Research Site	Cape Town
South Africa	Research Site	Cape Town
South Africa	Research Site	Plumstead
Spain	Research Site	Valencia
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Vinnytsia
United Kingdom	Research Site	West Bromwich
United States	Research Site	Amarillo	Texas
United States	Research Site	Atlanta	Georgia
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Beachwood	Ohio
United States	Research Site	Biloxi	Mississippi
United States	Research Site	Brownsburg	Indiana
United States	Research Site	Carrollton	Texas
United States	Research Site	Chula Vista	California
United States	Research Site	Clearwater	Florida
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Evansville	Indiana
United States	Research Site	Gurnee	Illinois
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Humble	Texas
United States	Research Site	Inverness	Florida
United States	Research Site	Kissimmee	Florida
United States	Research Site	Lakeland	Florida
United States	Research Site	Lancaster	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lincoln	California
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Marrero	Louisiana
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Mission Hills	California
United States	Research Site	Morehead City	North Carolina
United States	Research Site	Naples	Florida
United States	Research Site	New Port Richey	Florida
United States	Research Site	New York	New York
United States	Research Site	North Chesterfield	Virginia
United States	Research Site	Oak Lawn	Illinois
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Pflugerville	Texas
United States	Research Site	Phoenix	Arizona
United States	Research Site	Poway	California
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	Shawnee Mission	Kansas
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Springfield	Ohio
United States	Research Site	Sunnyside	New York
United States	Research Site	Tampa	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Topeka	Kansas
United States	Research Site	Tucson	Arizona
United States	Research Site	Uniontown	Pennsylvania
United States	Research Site	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Hungary,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Puerto Rico,  Russian Federation,  Slovakia,  South Africa,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with clinical remission	Clinical remission defined as: Modified Mayo Score (mMS): Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore = 0 or 1 AND at least a 1 point decrease from baseline	at Week 10
Secondary	Percentage of participants with sustained clinical remission	Sustained clinical remission defined as Modified Mayo Score (mMS): Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore = 0 or 1 AND at least a 1 point decrease from baseline	at both Week 10 and Week 54
Secondary	Percentage of participants with CS-free clinical remission	CS-free clinical remission defined as mMS: Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore = 0 or 1 AND at least a 1 point decrease from baseline	at Week 54 for patients who are CS-free for at least the last 12 weeks before the assessment at Week 54
Secondary	Percentage of participants with clinical response	Clinical response is defined as Reduction in mMS = 2 points from baseline AND = 30% from baseline AND a decrease in the rectal bleeding score = 1 point from baseline or a score of 0 or 1	at Week 10
Secondary	Percentage of participants with endoscopic improvement	Endoscopic improvement is defined as Endoscopy subscore = 1	at Week 10
Secondary	Serum concentration of brazikumab	Pharmacokinetics: concentration of brazikumab in serum	through Week 68
Secondary	For each dose level: LS mean of Mayo score and brazikumab pre-dose blood concentration	Exposure-response	at 12 weeks after dosing
Secondary	Incidence of anti-drug antibodies	Immunogenicity: incidence of brazikumab anti-drug antibodies in serum	through week 68
Secondary	Number and percentage of participants with adverse events	Number and percentage of patients with reported adverse events.	through Week 68
Secondary	Percentage of participants with potentially clinically significant changes in laboratory values	Percentage of patients with potentially clinically significant changes in hematology, clinical chemistry, urinalysis.	through Week 68
Secondary	Percentage of participants with potentially clinically significant changes in vital signs	Percentage of patients with potentially clinically significant changes in systolic and diastolic blood pressure, and pulse rate.	through Week 68
Secondary	Clinically relevant abnormal findings at physical exam	New or aggregated clinical relevant abnormal medical finding are reported as AE unless related to the disease under study	through Week 68
Secondary	Percentage of participants with potentially clinically significant changes in ECGs	Percentage of patients with potentially clinically significant changes in 12-lead ECG recordings	through Week 68