Clinical trial NCT03961815: Open-label Extension Study of Brazikumab in Crohn's Disease
Official title: An Open-label, Long-term Extension Study of Brazikumab in Participants With Moderately to Severely Active Crohn's Disease (INTREPID OLE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Crohn's Disease
IBD
Keywords: Crohn's Disease
Inflammatory bowel disease
Brazikumab
IL23 receptor
IBD
CD
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-05-23
Enrollment: 18
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 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.


Eligibility criteria: Inclusion Criteria:

1. 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):
   1. 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.
   2. 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.
2. Criterion deleted as part of Amendment.
3. 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).
4. 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.
5. 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.
6. 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.
7. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
8. Written informed consent from the participant has been obtained prior to any study related procedures.
9. Legally authorized representative consent has been obtained (if applicable).
10. Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable.
11. Demonstration of adequate compliance with the study procedures in Study D5271C00001 (Legacy #3150 301-008) in the opinion of the investigator and/or sponsor.
12. 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:

1. 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.
2. Current diagnosis of ischemic colitis, colonic mucosal dysplasia, or primary sclerosing cholangitis.
3. Organ or cell-based transplantation (eg, islet cell transplantation or autologous stem cell transplantation) with the exception of corneal transplant.
4. 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.
5. 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.
6. Participant meets criteria for discontinuation of study intervention during prior the D5271C00001 (Legacy #3150 301-008) study (excluding lack of efficacy).
7. Criterion deleted as part of Amendment.
8. Known history of primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, including HIV infection.
9. 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).
10. 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.
11. Participant requires additional immunosuppressive therapy (aside from permitted concomitant medication), biological treatment, or prohibited treatment.
12. 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.
13. Participant received a prohibited medication during participation in the lead-in study or during screening for this study.
14. 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.
15. Participants with a known hypersensitivity to brazikumab or any of the excipients of the product.
16. 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

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 ECGs
timeFrame: through Week 70
Secondary outcomes:
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Research Site
state: California
city: Clearwater
country: United States
facility: Research Site
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
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Beachwood
country: United States
facility: Research Site
state: Ohio
city: Houston
country: United States
facility: Research Site
state: Texas
city: Hamburg
country: Germany
facility: Research Site
city: Rzeszow
country: Poland
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
Study officials:
affiliation: AstraZeneca
name: Kathy Bohannon
role: STUDY_DIRECTOR
References: