Open-label Extension Study of Brazikumab in Crohn's Disease

Study Overview
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Brief Summary
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The purpose of Study D5271C00002 (Legacy #3150-303-008) is to permit participants in D5271C00001 (Legacy #3150-301-008) to receive open-label brazikumab in Study D5271C00002 (Legacy #3150-303-008). This will permit long-term observation of safety in these participants with brazikumab.

Official Title
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An Open-label, Long-term Extension Study of Brazikumab in Participants With Moderately to Severely Active Crohn's Disease (INTREPID OLE)

Conditions
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Crohn's Disease, IBD

Intervention / Treatment
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* Drug: Brazikumab Induction Dose
* Drug: Brazikumab Maintenance Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants with successful completion or early termination due to lack of efficacy from Study D5271C00001 (Legacy #3150-301-008). Meets 1 of the following criteria for successful completion or early termination due to lack of efficacy from Study D5271C00001 (Legacy #3150-301-008): A participant is considered to have completed the D5271C00001 (Legacy #3150-301-008) study if they have received scheduled study interventions, completed scheduled visits, and completed Week 52 assessments. A participant in Study D5271C00001 (Legacy #3150-301-008) who discontinued from the study due to lack of efficacy after a minimum of 12 weeks of double-blind treatment and met criteria for the use of rescue treatment in the lead-in protocol. Criterion deleted as part of Amendment. Each participant must have had the ileocolonoscopic procedure at the final visit (Week 52, Week 12, or early termination after Week 12 of Study D5271C00001 (Legacy # 3150-301-008). 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. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to signing the ICF without an alternative medical cause. Nonsterilized males who are sexually active with a female partner of childbearing potential must comply with the methods of contraception during treatment and until the end of relevant systemic exposure in the male participant, plus a further 18 weeks. 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. Legally authorized representative consent has been obtained (if applicable). Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable. Demonstration of adequate compliance with the study procedures in Study D5271C00001 (Legacy #3150 301-008) in the opinion of the investigator and/or sponsor. Willingness and ability to attend all study visits, comply with the study procedures, read and write in order to complete questionnaires, and be able to complete the study. Complete inclusion criteria are in the study protocol Exclusion Criteria: Any participant with an unresolved AE from the Study D5271C00001 (Legacy #3150 301-008) that would limit the participant's ability to participate in or complete this study. Current diagnosis of ischemic colitis, colonic mucosal dysplasia, or primary sclerosing cholangitis. Organ or cell-based transplantation (eg, islet cell transplantation or autologous stem cell transplantation) with the exception of corneal transplant. 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. History of cancer except for basal cell and/or squamous cell carcinoma of the skin, and carcinoma in situ of the cervix within 12 months of screening. Participant meets criteria for discontinuation of study intervention during prior the D5271C00001 (Legacy #3150 301-008) study (excluding lack of efficacy). Criterion deleted as part of Amendment. Known history of primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, including HIV infection. Prolonged QTcF interval (QTc >450 msec or QTC >480 for participants with bundle branch block; determined by central ECG), or conditions leading to additional risk for QT prolongation (eg, congenital long-QT syndrome). 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 MDRD equation, as applicable, by the central laboratory at screening are excluded. Participant requires additional immunosuppressive therapy (aside from permitted concomitant medication), biological treatment, or prohibited treatment. Participant received a Bacille Calmette-Guérin vaccination within 12 months of Week 0 (Visit 1) or any other live vaccine < 4 weeks prior to Week 0 (Visit 1) or is planning to receive any such vaccine over the course of the study. Participant received a prohibited medication during participation in the lead-in study or during screening for this study. Participant is planning to receive an investigational drug (other than study intervention) or investigational device at any time during Study D5271C00002 (Legacy #3150-303-008) with the exception of registry or cohort trials. Participants with a known hypersensitivity to brazikumab or any of the excipients of the product. Protocol-defined abnormal laboratory results at screening. 17. Females who are pregnant, nursing, or planning a pregnancy during the study OR females who are of childbearing potential and do not agree to use a highly effective method of contraception consistently and correctly. 18 Participant is directly or indirectly involved in the conduct and administration of this study as an investigator, subinvestigator, study coordinator, other study staff member, or employee of AstraZeneca, 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. 19 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 20 Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. 21 Previous participation in the present study. Complete exclusion criteria are in the study protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brazikumab Induction Dose<br>Administer at Week 0, Week 4, and Week 8 | Drug: Brazikumab Induction Dose<br>* Participants who met criteria for early termination due to lack of efficacy (rescue treatment criteria) or who did not meet CDAI response at Week 52 in the lead-in study D5121C00001 are considered inadequate/non responders, and will receive IV induction dosing brazikumab at Week 0, Week 4, and Week 8 followed by maintenance dosing of brazikumab subcutaneously every 4 weeks thereafter up to Week 52.<br>|
| Experimental: Brazikumab Maintenance Dose<br>Administer at 4-week intervals through Week 52 Participants who receive IV induction dosing will be administered brazikumab SC at 4-week intervals starting Week 12 through Week 52 | Drug: Brazikumab Maintenance Dose<br>* Responders from Lead-In study D5271C00001 who completed requirements through Week 52 and met CDAI response (CDAI score of < 150 points or CDAI reduction from Baseline of ≥ 100 points) without ongoing rescue treatment at Week 52 in the lead-in study. will receive maintenance dose of brazikumab administered subcutaneously every 4 weeks through Week 52, starting at Week 0. The subcutaneous dose of brazikumab will be administered to all responders/completers in the lead-in study regardless of the prior treatment administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of patients with adverse events | Number and percentage of patients with reported adverse events. | through Week 70 | 
| Percentage of patients with potentially clinically significant changes in laboratory values | Percentage of patients with potentially clinically significant changes in hematology, clinical chemistry, urinalysis. | through Week 70 | 
| Percentage of patients with potentially clinically significant changes in vital signs | Percentage of patients with potentially clinically significant changes in systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate. | through Week 70 | 
| Percentage of patients with potentially clinically significant changes in ECGs | Percentage of patients with potentially clinically significant changes in 12-lead ECG recordings. | through Week 70 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, Inflammatory bowel disease, Brazikumab, IL23 receptor, IBD, CD