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

Sponsor

AstraZeneca (Industry)

Overall Status

Enrolling by invitation

CT.gov ID

NCT03961815

Collaborator

(none)

161

Enrollment

127

Locations

Arms

63.2

Anticipated Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease IBD	Drug: Brazikumab Induction Dose Drug: Brazikumab Maintenance Dose	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

161 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 6, 2020

Anticipated Primary Completion Date :

Apr 14, 2025

Anticipated Study Completion Date :

Apr 14, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brazikumab Induction Dose Administer at Week 0, Week 4, and Week 8	Drug: Brazikumab Induction Dose 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.
Experimental: Brazikumab Maintenance Dose 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 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

Arm

Intervention/Treatment

Experimental: Brazikumab Induction Dose

Administer at Week 0, Week 4, and Week 8

Drug: Brazikumab Induction Dose

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.

Experimental: Brazikumab Maintenance Dose

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

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

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Lincoln	California	United States	95648
2	Research Site	Clearwater	Florida	United States	33756
3	Research Site	Kissimmee	Florida	United States	34741
4	Research Site	Lakeland	Florida	United States	33813
5	Research Site	Miami	Florida	United States	33157
6	Research Site	Miami	Florida	United States	33165
7	Research Site	Tampa	Florida	United States	33626
8	Research Site	Beachwood	Ohio	United States	44122
9	Research Site	Houston	Texas	United States	77058
10	Research Site	McKinney	Texas	United States	75071
11	Research Site	Steyr		Austria	4400
12	Research Site	New Westminster	British Columbia	Canada	V3L 3W4
13	Research Site	Hamilton	Ontario	Canada	L8N 3Z5
14	Research Site	Chicoutimi	Quebec	Canada	G7H 5H6
15	Research Site	Ceske Budejovice		Czechia	370 01
16	Research Site	Horovice		Czechia	26831
17	Research Site	Hradec Kralove		Czechia	500 12
18	Research Site	Ostrava		Czechia	702 00
19	Research Site	Usti nad Labem		Czechia	401 13
20	Research Site	Amiens Cedex 1		France	80054
21	Research Site	Clermont Ferrand		France	63003
22	Research Site	Clichy Cedex		France	92118
23	Research Site	Montpellier CEDEX 5		France	34295
24	Research Site	Nice		France	06200
25	Research Site	Paris		France	75018
26	Research Site	Reims		France	51092
27	Research Site	Augsburg		Germany	86156
28	Research Site	Berlin		Germany	10825
29	Research Site	Hamburg		Germany	20251
30	Research Site	Kiel		Germany	24105
31	Research Site	Minden		Germany	32423
32	Research Site	Remscheid		Germany	42859
33	Research Site	Ulm		Germany	89081
34	Research Site	Budapest		Hungary	1033
35	Research Site	Budapest		Hungary	1082
36	Research Site	Debrecen		Hungary	4032
37	Research Site	Kecskemét		Hungary	6000
38	Research Site	Ahemdabad		India	380054
39	Research Site	Bangalore		India	560054
40	Research Site	Hyderabad		India	500032
41	Research Site	Jaipur		India	302001
42	Research Site	New Delhi		India	110017
43	Research Site	New Delhi		India	110075
44	Research Site	Rajkot		India	360004
45	Research Site	Secunderabad		India	500003
46	Research Site	Surat		India	395002
47	Research Site	Wardha		India	442004
48	Research Site	Haifa		Israel	3109601
49	Research Site	Jerusalem		Israel	9103102
50	Research Site	Kfar Saba		Israel	4428164
51	Research Site	Petah Tikva		Israel	4941492
52	Research Site	Belluno		Italy	32100
53	Research Site	Castellana Grotte		Italy	70013
54	Research Site	Firenze		Italy	50134
55	Research Site	Garbagnate Milanese		Italy	20024
56	Research Site	Milano		Italy	20132
57	Research Site	Milano		Italy	20154
58	Research Site	Napoli		Italy	80131
59	Research Site	Padova		Italy	35128
60	Research Site	Palermo		Italy	90127
61	Research Site	Pavia		Italy	27100
62	Research Site	Roma		Italy	00157
63	Research Site	Rozzano		Italy	20089
64	Research Site	Busan		Korea, Republic of	48108
65	Research Site	Daegu		Korea, Republic of	42415
66	Research Site	Seoul		Korea, Republic of	03722
67	Research Site	Seoul		Korea, Republic of	06351
68	Research Site	Seoul		Korea, Republic of	06591
69	Research Site	Seoul		Korea, Republic of	156-755
70	Research Site	Wonju-si		Korea, Republic of	26426
71	Research Site	Bydgoszcz		Poland	85 168
72	Research Site	Bydgoszcz		Poland	85-079
73	Research Site	Chojnice		Poland	89-600
74	Research Site	Kielce		Poland	25-355
75	Research Site	Kraków		Poland	31-513
76	Research Site	Rzeszow		Poland	35-302
77	Research Site	Sopot		Poland	81-756
78	Research Site	Toruń		Poland	87-100
79	Research Site	Warszawa		Poland	00-635
80	Research Site	Warszawa		Poland	02-507
81	Research Site	Warszawa		Poland	03-580
82	Research Site	Wrocław		Poland	52-210
83	Research Site	Aramil		Russian Federation	624002
84	Research Site	Izhevsk		Russian Federation	426035
85	Research Site	Kazan		Russian Federation	420008
86	Research Site	Kemerovo		Russian Federation	650000
87	Research Site	Krasnodar		Russian Federation	350072
88	Research Site	Moscow		Russian Federation	115419
89	Research Site	Novosibirsk		Russian Federation	630007
90	Research Site	Perm		Russian Federation	614000
91	Research Site	Saint-Petersburg		Russian Federation	195257
92	Research Site	Saint-Petersburg		Russian Federation	196143
93	Research Site	Tomsk		Russian Federation	634050
94	Research Site	Banska Bystrica		Slovakia	97401
95	Research Site	Bratislava		Slovakia	81108
96	Research Site	Bratislava		Slovakia	851 07
97	Research Site	Kosice		Slovakia	04013
98	Research Site	Nitra		Slovakia	94901
99	Research Site	Bloemfontein		South Africa	9301
100	Research Site	Cape Town		South Africa	7500
101	Research Site	Johannesburg		South Africa	1827
102	Research Site	Plumstead		South Africa	7800
103	Research Site	Pretoria		South Africa	0002
104	Research Site	Madrid		Spain	28046
105	Research Site	Pamplona		Spain	31008
106	Research Site	Pontevedra		Spain	36071
107	Research Site	Sevilla		Spain	41009
108	Research Site	Tomelloso		Spain	13700
109	Research Site	Valencia		Spain	46010
110	Research Site	Kaohsiung		Taiwan	807
111	Research Site	Taichung		Taiwan	40201
112	Research Site	Taichung		Taiwan	40443
113	Research Site	Taipei City		Taiwan	114
114	Research Site	Taipei		Taiwan	100
115	Research Site	Taipei		Taiwan	11217
116	Research Site	Kharkiv		Ukraine	61037
117	Research Site	Kherson		Ukraine	73000
118	Research Site	Kyiv		Ukraine	01023
119	Research Site	Kyiv		Ukraine	03680
120	Research Site	Kyiv		Ukraine	04050
121	Research Site	Kyiv		Ukraine	04078
122	Research Site	Lviv		Ukraine	79059
123	Research Site	Ternopil		Ukraine	46001
124	Research Site	Vinnytsia		Ukraine	21009
125	Research Site	Coventry		United Kingdom	CV2 2DX
126	Research Site	Nottingham		United Kingdom	NG7 2UH
127	Research Site	West Bromwich		United Kingdom	B71 4HJ