Clinical trial NCT04277546: Open-label Extension Study of Brazikumab in Ulcerative Colitis
Official title: A Phase 2 Open-label, Long-term Extension Safety Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis (EXPEDITION OLE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ulcerative Colitis
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-02-20
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this OLE Study D5272C00002 (Legacy #3151-202-008) is to permit participants who previously enrolled in the double-blind Study D5272C00001 (Legacy #3151-201-008) to receive brazikumab, allowing for long-term observation of safety and efficacy in these participants treated with brazikumab. There are no formal hypotheses to be tested. Safety and efficacy data obtained in this study will be included in regulatory product submissions as appropriate.


Eligibility criteria: Inclusion Criteria:

1.01 Male or female participants who: successfully completed or discontinued participation due to lack of efficacy after Week 10 in the lead-in Study D5272C00001 (Legacy #3151-201-008). AND Meets 1 of the following criteria for successful completion or early termination from Study D5272C00001 (Legacy #3151-201-008):

1. Participant completed Study D5272C00001 (Legacy #3151-201-008), received scheduled study interventions, completed scheduled visits, and completed Week 54 assessments.
2. Participant discontinued participation due to lack of efficacy after Week 10 in Study D5272C00001 (Legacy #3151-201-008), received scheduled study interventions, and completed Early Termination Visit assessments.

1.02. Deleted Eligibility as part of Amendment 2 1.03. Deleted Eligibility as part of Amendment 3 1.04. Deleted eligibility as part of Amendment 2 2.01. Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. Nonsterilized men who are sexually active with a female partner of childbearing potential should use condom during treatment and for 18 weeks after the last dose of study intervention, must comply with the methods of contraception described in Criterion 2.02 below, and must not donate or bank sperm for fertilization purpose for the same time period.

2.02. 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 (confirmed by the investigator) from signing the ICF throughout the study duration and for at least 18 weeks after last dose of study intervention 2.03. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal.

3.01. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Written informed consent from the participant has been obtained prior to any study related procedures.

Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health and Research Study Information \[US sites\] and written Data Protection consent \[EU sites\]).

4.01. Demonstration of adequate compliance with the study procedures in Study D5272C00001 (Legacy #3151-201-008), in the opinion of the investigator and/or sponsor.

4.02. Willingness and ability to attend all study visits, comply with the study procedures, and be able to complete the study period.

5.01 Participant must be 18 to 80 years of age inclusive, at the time of signing the ICF.

Complete inclusion criteria are in the study protocol

Exclusion Criteria:

1.01. Any participant with an unresolved AE from the lead-in study that, in the investigator's opinion, would limit the participant's ability to participate in or complete this study. Any unresolved AE related to an infection will require further discussion with the study physician/designee prior to enrollment.

1.02. Current diagnosis of fulminant colitis, CD or indeterminate colitis, presence of a fistula consistent with CD, primary sclerosing cholangitis, celiac disease, or toxic megacolon. Bile acid malabsorption and other conditions that may potentially confound assessments must be treated prior to baseline.

1.03. Organ or cell-based transplantation with the exception of corneal transplant.

1.04. Any other condition or finding that, in the investigator's or sponsor's opinion, would either confound proper interpretation of the study or expose a participant to unacceptable risk.

1.05. The following are exclusionary with regards to malignancy:

1. Evidence of intestinal epithelial dysplasia on endoscopy, and this is confirmed on biopsy, the participant must be excluded.
2. Any diagnosis of malignancy that requires discontinuation of study intervention from lead-in study.
3. Any new diagnosis of malignancy after completion of the lead-in study. d) Carcinoma in situ of the cervix, with apparent successful curative therapy within 12 months prior to Week 0.

1.06. Participant meets criteria for discontinuation of study intervention during prior lead-in study.

1.07. Deleted exclusion criterion as part of Amendment 3 1.08. Known history of primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, including HIV infection.

1.09. Prolonged QTcF interval or conditions leading to additional risk for QT prolongation. Participants with electrolyte abnormalities such as hypokalemia and hypomagnesemia that would increase the risk of QT prolongation are to be corrected prior to enrollment.

1.010. Clinically significant kidney disease including but not limited to:

(a) Chronic kidney disease with an estimated glomerular filtration rate of less than 30 ml/min calculated by Modification of Diet in Renal Disease equation, asapplicable, by the central laboratory at screening are excluded.

2.01. Participant requires additional immunosuppressive therapy (aside from permitted concomitant medication in the protocol), biological treatment or prohibited treatment 2.02. Deleted eligibility as part of Amendment 2 2.03. Participant received a prohibited medication during participation in the D5272C00001 (Legacy #3151-201-008) study.

2.04. Participant received a Bacille Calmette-Guérin vaccination within 12 months of Week 0 or any other live vaccine \< 4 weeks prior to Week 0, or is planning to receive any such vaccine over the course of the study.

2.05. Participant has received an investigational product after discontinuation from Study D5272C00001 (Legacy #3151-201-008) and prior to enrolling in this study or participant is planning to receive an investigational drug (other than study intervention) or investigational device at any time during Study D5272C00002 (Legacy #3151-202-008).

3.01. Participant who discontinued participation due to lack of efficacy after Week 10 in Study D5272C00001 and did not receive all 3 IV infusions of study interventions scheduled for Week 0 (Day 1), Week 2 (Day 15), and Week 6 (Day 43), and SC at Week 10 (Day 71) in accordance with the protocol for Study D5272C00001.

3.02. Participant who discontinued due to lack of efficacy after Week 10 in Study D5272C00001 (Legacy #3151-201-008) but currently demonstrates clinical response and/or meets endoscopic Mayo Score of 0 or 1 prior to Week 54 in Study D5272C00001 (Legacy #3151-201-008): Clinical Response 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, in Study D5272C00001 (Legacy #3151-201-008). Note: Participants are encouraged to remain in the lead-in Study D5272C00001 (Legacy #3151-201-008) if the participant is demonstrating evidence of clinical response. Participants should not early terminate that study due to lack of efficacy if this exclusion is met.

4.01. Abnormal laboratory results at screening as described in the protocol. 5.01. Females who are pregnant, breast feeding, or planning a pregnancy during the study OR females who are of childbearing potential and do not agree to use contraception consistently and correctly as required by the study protocol.

5.02. Participant is directly or indirectly involved in the planning and/or conduct and administration of this study as study staff member, or employee of the sponsor, or the participant is a first-degree family member, significant other, or relative residing with one of the above persons involved directly or indirectly in the study; or the participant is enrolled in this study at another clinical study site.

5.03. Judgment that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.

5.04. Previous enrollment in the present study.

Complete exclusion criteria are in the study protocol

Primary outcomes:
measure: Number and percentage of patients with adverse events
timeFrame: Through week 70
measure: Percentage of patients with potentially clinically significant changes in laboratory values
timeFrame: Through week 70
measure: Percentage of patients with potentially clinically significant changes in vital signs
timeFrame: Through week 70
measure: Percentage of patients with potentially clinically significant changes in physical exams
timeFrame: Through week 70
measure: Percentage of patients with potentially clinically significant changes in ECGs
timeFrame: Through week 70
Secondary outcomes:
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Research Site
state: California
city: Lancaster
country: United States
facility: Research Site
state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
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
facility: Research Site
state: Florida
city: Evansville
country: United States
facility: Research Site
state: Indiana
city: Beachwood
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Humble
country: United States
facility: Research Site
state: Texas
city: Ceske Budejovice
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: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Rho
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Kasama-shi
country: Japan
facility: Research Site
city: Kashiwa-shi
country: Japan
facility: Research Site
city: Minato-ku
country: Japan
facility: Research Site
city: Wonju-si
country: Korea, Republic of
facility: Research Site
city: Kraków
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: San Juan
country: Puerto Rico
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: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Kathy Bohannon
role: STUDY_DIRECTOR
References: