History of Changes for Study: NCT02407236

A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UNIFI)

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Study Record Versions

Version	Submitted Date	Changes
1	March 30, 2015	None (earliest Version on record)
2	April 20, 2015	Study Status
3	May 11, 2015	Study Status
4	June 1, 2015	Study Status
5	July 14, 2015	Study Status
6	August 11, 2015	Study Status and Contacts/Locations
7	September 23, 2015	Contacts/Locations and Study Status
8	October 16, 2015	Recruitment Status, Contacts/Locations and Study Status
9	November 6, 2015	Contacts/Locations and Study Status
10	November 27, 2015	Contacts/Locations and Study Status
11	December 21, 2015	Contacts/Locations and Study Status
12	January 12, 2016	Contacts/Locations and Study Status
13	February 2, 2016	Contacts/Locations and Study Status
14	February 23, 2016	Contacts/Locations and Study Status
15	March 15, 2016	Contacts/Locations and Study Status
16	April 5, 2016	Contacts/Locations and Study Status
17	April 22, 2016	Contacts/Locations and Study Status
18	May 13, 2016	Contacts/Locations and Study Status
19	June 1, 2016	Contacts/Locations and Study Status
20	June 22, 2016	Contacts/Locations and Study Status
21	July 13, 2016	Contacts/Locations and Study Status
22	August 3, 2016	Contacts/Locations and Study Status
23	August 24, 2016	Contacts/Locations and Study Status
24	October 14, 2016	Contacts/Locations and Study Status
25	November 12, 2016	Contacts/Locations, Study Status and Oversight
26	December 12, 2016	Contacts/Locations and Study Status
27	February 10, 2017	Contacts/Locations and Study Status
28	March 10, 2017	Study Status and Contacts/Locations
29	March 21, 2017	Contacts/Locations and Study Status
30	April 20, 2017	Contacts/Locations, Study Status and Oversight
31	May 16, 2017	Study Status and Contacts/Locations
32	June 13, 2017	Contacts/Locations and Study Status
33	July 11, 2017	Study Status and Contacts/Locations
34	August 8, 2017	Contacts/Locations and Study Status
35	September 6, 2017	Recruitment Status, Contacts/Locations, Study Status and Study Design
36	November 28, 2017	Study Status and Contacts/Locations
37	February 26, 2018	Study Status and Contacts/Locations
38	March 21, 2018	Study Status and Study Design
39	August 13, 2018	Study Status and Study Design
40	October 3, 2018	Study Status
41	October 31, 2018	Study Design and Study Status
42	November 28, 2018	Study Status and Study Design
43	March 21, 2019	Study Status and Study Design
44	April 18, 2019	Study Status and Contacts/Locations
45	May 16, 2019	Study Status and Study Design
46	June 13, 2019	Study Status
47	August 8, 2019	Study Status
48	August 26, 2019	Arms and Interventions and Study Status
49	October 31, 2019	Study Status
	Results Submission Events
November 15, 2019		Returned after QC review: December 4, 2019
50	December 20, 2019	Outcome Measures, Study Status, More Information, Document Section, Adverse Events, Baseline Characteristics, Participant Flow and Study Design
51	January 21, 2020	Study Status
52	February 18, 2020	Study Status and Contacts/Locations
53	March 17, 2020	Study Status
54	April 14, 2020	Study Status and Contacts/Locations
55	May 12, 2020	Study Status
56	July 7, 2020	Study Status
57	September 29, 2020	Study Status and Contacts/Locations
58	October 27, 2020	Study Status
59	November 24, 2020	Study Status
60	December 22, 2020	Contacts/Locations and Study Status
61	January 19, 2021	Study Status
62	March 16, 2021	Study Status
63	April 12, 2021	Study Status
64	May 11, 2021	Study Status
65	June 7, 2021	Study Status
66	July 6, 2021	Study Status
67	August 3, 2021	Contacts/Locations and Study Status
68	August 31, 2021	Study Status
69	September 28, 2021	Study Status
70	October 26, 2021	Study Status
71	November 23, 2021	Study Status
72	February 2, 2022	Recruitment Status and Study Status
73	August 2, 2022	Study Status and Contacts/Locations
74	November 29, 2022	Adverse Events, Participant Flow, Baseline Characteristics, Study Status, Document Section and More Information
75	January 3, 2023	Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	CR106920
Brief Title:	A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UNIFI)
Official Title:	A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Protocol to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis
Secondary IDs:	2014-005606-38 [EudraCT Number] CNTO1275UCO3001 [Janssen Research & Development, LLC]

Study Status


Record Verification:	March 2015
Overall Status:	Not yet recruiting
Study Start:	June 2015
Primary Completion:	April 2018 [Anticipated]
Study Completion:	July 2021 [Anticipated]

First Submitted:	March 30, 2015
First Submitted that Met QC Criteria:	March 30, 2015
First Posted:	April 2, 2015 [Estimate]

Last Update Submitted that Met QC Criteria:	March 30, 2015
Last Update Posted:	April 2, 2015 [Estimate]

Sponsor/Collaborators


Sponsor:	Janssen Research & Development, LLC
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:	Yes

Study Description

Brief Summary:

The purpose of this study is to evaluate the efficacy and safety of ustekinumab as intravenous (IV: into the vein) infusion in induction study in participants with moderately to severely active Ulcerative Colitis (UC) and as subcutaneous (SC) administration in maintenance study in participants with moderately to severely active Ulcerative Colitis (UC) who have demonstrated a clinical response to Induction treatment with IV ustekinumab.

Detailed Description:

This is a Phase 3, randomized (assignment of study drug by chance), double-blind (neither the participant or study staff will know the identity of study drugs), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (a medical research study comparing the response in 2 or more groups of participants receiving different interventions), multi-center (more than one clinical site will work on a medical research study), protocol of ustekinumab. The protocol will consist of 2 studies: an Induction study and a Maintenance study with unique endpoints. Screening period will be up to 8 Weeks. Induction study will be at least 8 weeks duration for each participant. Participant with clinical response in the Induction study will be eligible for the Maintenance study. The Maintenance study will be 44 weeks duration. After completion of the maintenance study, a long term extension will follow eligible participants for an additional 3 years. Clinical remission will be evaluated at Week 8 in the Induction study. Clinical remission among ustekinumab Induction responders will be evaluated at week 44 in the Maintenance study. Participants' safety will be monitored throughout.

Conditions


Conditions:	Colitis, Ulcerative Inflammatory Bowel Diseases
Keywords:	Ustekinumab Inflammatory Bowel Diseases (IBD) Colitis, Ulcerative

Study Design


Study Type:	Interventional
Primary Purpose:	Other
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	10
Masking:	Double (Participant, Investigator)
Allocation:	Randomized
Enrollment:	951 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Placebo Comparator: Induction Study - Placebo Intravenous (IV) Participants will be randomized to receive single dose of placebo as Intravenous (IV: into the vein) infusion at Week 0. Participants with clinical response at Week 8 will be eligible to enter the Maintenance study, but will not be randomized.	Drug: Placebo IV Placebo will be administered as intravenous infusion.
Experimental: Induction Study - Ustekinumab 130 milligram (mg) IV Participants will be randomized to receive single dose of ustekinumab 130 mg as IV infusion at Week 0. Participants with clinical response at Week 8 will be eligible to enter the Maintenance study and will be randomized.	Drug: Ustekinumab IV Ustekinumab will be administered as intravenous infusion at Week 0 or Week 8 in Induction Study.
Experimental: Induction Study - Ustekinumab 6 mg/kg IV Participants will be randomized to receive ustekinumab approximating 6 mg/kg of body weight, as intravenous infusion at Week 0. Participants with clinical response at Week 8 will be eligible to enter the Maintenance study and will be randomized.	Drug: Ustekinumab IV Ustekinumab will be administered as intravenous infusion at Week 0 or Week 8 in Induction Study.
Induction Study- Placebo- Nonresponsders at Week 8 Participants without clinical response to placebo at Week 8 will receive a single IV infusion of ustekinumab approximating 6mg/kg along with matching subcutaneous (SC) placebo (to maintain the blind). Participants in clinical response at Week 16 will be eligible to enter Maintenance study and will be randomized.	Drug: Ustekinumab IV Ustekinumab will be administered as intravenous infusion at Week 0 or Week 8 in Induction Study.
Induction study-Ustekinumab Nonresponders at Week 8 Participants without clinical response to ustekinumab (130 mg or 6 mg/kg [IV]) at Week 8 will receive a single dose of ustekinumab 90 mg subcutaneously along with matching placebo intravenously (to maintain the blind). Participants in clinical response at Week 16 (that is, delayed responders) will be eligible to enter Maintenance study, but will not be randomized.	Drug: Ustekinumab SC Ustekinumab will be administered as subcutaneously.
Placebo Comparator: Maintenance Study - Placebo Subcutaneous (SC) Participants in clinical response (at Week 8 or Week 16) to Induction treatment with single IV infusion of Ustekinumab will be randomized to receive placebo subcutaneously, beginning Week 0 of Maintenance study through Week 44.	Drug: Placebo SC Placebo will be administered Subcutaneously.
Experimental: Maintenance Study - Ustekinumab 90mg SC every 12 weeks Participants in clinical response (at Week 8 or Week 16) to Induction treatment with single IV infusion of Ustekinumab will be randomized to receive ustekinumab 90 mg subcutaneously every 12 weeks, beginning Week 0 of Maintenance study through Week 44.	Drug: Ustekinumab SC Ustekinumab will be administered as subcutaneously.
Experimental: Maintenance Study - Ustekinumab 90mg SC every 8 weeks (q8w) Participants in clinical response (at Week 8 or Week 16) to Induction treatment with single IV infusion of Ustekinumab will be randomized to receive ustekinumab 90 mg subcutaneously every 8 weeks, beginning Week 0 of Maintenance study through Week 44.	Drug: Ustekinumab SC Ustekinumab will be administered as subcutaneously.
Maintenance Study - Placebo IV - Responder - Placebo SC Participants in clinical response to Induction treatment with IV Placebo will receive placebo subcutaneously, beginning Week 0 of Maintenance study through Week 44. Participants are not randomized.	Drug: Placebo SC Placebo will be administered Subcutaneously.
Maintenance Study-Delayed Responder-Ustekinumab 90mg SC q8w Participants without clinical response to induction treatment ustekinumab (130 mg or 6 mg/kg [IV]) at Week 8 but in clinical response at Week 16 after receiving Induction Ustekinumab at week 8 (delayed responders) will receive ustekinumab 90 mg subcutaneously every 8 weeks, beginning Week 0 of Maintenance study through Week 44. Participants are not randomized.	Drug: Ustekinumab SC Ustekinumab will be administered as subcutaneously.

Outcome Measures


Primary Outcome Measures:
1.	Induction Study - Number of Participants With Clinical Remission [ Time Frame: Week 8 ] The global definition of Clinical remission is defined as Mayo score less than or equal to (<=) 2 points, with no individual subscore greater than (>) 1, for countries outside the United States (US). For the US, Clinical remission is defined as absolute stool number <=3, a rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.
2.	Maintenance Study - Number of Participants with Clinical Remission Among Participants in Clinical Response to IV Ustekinumab Induction Treatment [ Time Frame: Week 44 ] The global definition of Clinical remission is defined as Mayo score less than or equal to (<=) 2 points, with no individual subscore greater than (>) 1, for countries outside the United States (US). For the US Clinical remission is defined as absolute stool number <=3, a rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.
Secondary Outcome Measures:
1.	Induction Study - Number of Participants with Clinical Response [ Time Frame: Week 8 ] Clinical response is defined as a decreased from Induction baseline in the Mayo score by greater than or equal to (>=) 30 percent (%) and >=3 points, with either a decrease from induction baseline in the rectal bleeding subscore >=1 or rectal bleeding subscore = 0 or 1.
2.	Induction Study - Number of Participants With Endoscopic Healing [ Time Frame: Week 8 ] Endoscopic healing is improvement in the endoscopic appearance of the mucosa. It will be defined as Mayo endoscopic subscore = 0 or 1.
3.	Induction Study - Mean Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score [ Time Frame: Week 8 ] The IBDQ is a 32-item questionnaire for participants with Inflammatory Bowel Disease (IBD) that will be used to evaluate the disease-specific health-related quality of life across 4 dimensional scores: bowel (loose stools, abdominal pain), systemic (fatigue, altered sleep pattern), social (work attendance, need to cancel social events), and emotional (anger, depression, irritability). The total score ranges from 32 to 224 with higher scores indicating better quality of life.
4.	Maintenance Study - Number of Participants with Clinical Response Among Participants in Clinical Response to IV Ustekinumab Induction Treatment [ Time Frame: Through Week 44 ] Clinical response is defined as a decreased from Induction baseline in the Mayo score by greater than or equal to (>=) 30 percent (%) and >=3 points, with either a decrease from Induction baseline in the rectal bleeding subscore >=1 or rectal bleeding subscore = 0 or 1.
5.	Maintenance Study - Number of Participants with Endoscopic Healing Among Participants in Clinical Response to IV Ustekinumab Induction Treatment [ Time Frame: Week 44 ] Endoscopic healing is improvement in the endoscopic appearance of the mucosa. It will be defined as Mayo endoscopic subscore = 0 or 1.
6.	Maintenance Study - Number of Participants with Clinical Remission Among those who Achieved Clinical Remission at Maintenance Study Baseline [ Time Frame: Through Week 44 ] The global definition of Clinical remission is defined as Mayo score less than or equal to (<=) 2 points, with no individual subscore greater than (>) 1, for countries outside the United States (US). For the US Clinical remission is defined as absolute stool number <=3, a rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1. The Mayo score is a tool designed to measure disease activity for ulcerative colitis.
7.	Maintenance Study - Number of Participants with Clinical Remission and not Receiving Concomitant Corticosteroids Among those Receiving Concomitant Corticosteroids at Maintenance Baseline [ Time Frame: Week 44 ] The global definition of Clinical remission is defined as Mayo score less than or equal to (<=) 2 points, with no individual subscore greater than (>) 1, for countries outside the United States (US). For the US Clinical remission is defined as absolute stool number <=3, a rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1. The Mayo score is a tool designed to measure disease activity for ulcerative colitis.

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Has a clinical diagnosis of Ulcerative Colitis (UC) at least 3 months before Screening Has moderately to severely active UC, defined as a Baseline (Week 0) Mayo score of 6 to 12, including a Screening endoscopy subscore of the Mayo score greater than or equal to (>=) 2 as determined by a central reading of the video endoscopy Have failed biologic therapy, that is, have received treatment with 1 or more tumour necrosis factor (TNF) antagonists or vedolizumab at a dose approved for the treatment of UC, and have a documented history of failure to respond to or tolerate such treatment; OR Be naïve to biologic therapy (TNF antagonists or vedolizumab) or have received biologic therapy but have not demonstrated a history of failure to respond to, or tolerate, a biologic therapy and have a prior or current UC medication history that includes at least 1 of the following: a. Inadequate response to or failure to tolerate current treatment with oral corticosteroids or immunomodulators (6-mercaptopurine [6-MP] or azathioprine [AZA]) OR b. History of failure to respond to, or tolerate, at least 1 of the following therapies: oral or IV corticosteroids or immunomodulators (6-MP or AZA) OR c. History of corticosteroid dependence (that is, an inability to successfully taper corticosteroids without a return of the symptoms of UC) Before the first administration of study agent, the following conditions must be met: vedolizumab must have been discontinued for at least 4 months and anti-tumor necrosis factors (TNFs) for at least 8 weeks Exclusion Criteria: Has severe extensive colitis and is at imminent risk of colectomy Has UC limited to the rectum only or to < 20 centimeters (cm) of the colon Presence of a stoma or history of a fistula Participants with history of extensive colonic resection (for example, less than 30 cm of colon remaining) that would prevent adequate evaluation of the effect of study agent on clinical disease activity Participants with history of colonic mucosal dysplasia. Participants will not be excluded from the study because of a pathology finding of "indefinite dysplasia with reactive atypia''

Contacts/Locations


Central Contact Person:	This study is not yet recruiting patients. Please check back for future recruiting sites, or email Email: JNJ.CT@sylogent.com
Study Officials:	Janssen Research & Development, LLC Clinical Trial Study Director Janssen Research & Development, LLC
Locations:

IPDSharing


Plan to Share IPD:

References


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