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 - UNIFI

• Register: EUCTR
• Last refreshed on: 21 December 2021
• Main ID: EUCTR2014-005606-38-DK
• Date of registration: 30/06/2015
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public 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 - UNIFI
• Scientific 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 - UNIFI
• Date of first enrolment: 02/11/2015
• Target sample size: 951
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005606-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 10
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, United Kingdom, United States

Contacts

• Name: -
• Affiliation: PAREXEL International LLC

• Name: -
• Affiliation: PAREXEL International LLC

Key inclusion & exclusion 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 antitumor necrosis factors (TNFs) [ or approved biosimilars for these therapies] for at least 8 weeks
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 751
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

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''


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Name: Ustekinumab
Product Code: CNTO1275
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Ustekinumab
CAS Number: 815610-63-0
Current Sponsor code: CNTO1275
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: STELARA®
Product Name: Ustekinumab
Product Code: CNTO1275
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Ustekinumab
CAS Number: 815610-63-0
Current Sponsor code: CNTO1275
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 90-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Induction study:
- Week 8

Maintenance study:
- Week 44

Secondary Objective: Induction
efficacy of IV ustekinumab in inducing endoscopic healing
efficacy of IV ustekinumab in inducing clinical response
impact of IV ustekinumab on disease-specific health-related quality of life
efficacy of ustekinumab treatment on mucosal healing
efficacy of induction therapy with IV ustekinumab by biologic failure status
PK, immunogenicity, and PD of ustekinumab induction therapy

Maintenance
efficacy in maintaining clinical response in subjects induced into clinical response with ustekinumab
endoscopic healing in subjects induced into clinical response
efficacy of ustekinumab in achieving corticosteroid-free clinical remission
efficacy of ustekinumab in maintaining clinical remission
efficacy of ustekinumab treatment on mucosal healing
impact of SC ustekinumab on disease-specific health-related quality of life
efficacy of maintenance therapy with SC ustekinumab by biologic failure status
PK, immunogenicity, and PD of ustekinumab maintenance therapy

Main Objective: Induction study:
-To evaluate the efficacy of IV ustekinumab in inducing clinical remission in subjects with moderately to severely active ulcerative colitis (UC).
-To evaluate the safety of IV ustekinumab in subjects with moderately to severely active UC.

Maintenance study:
- To evaluate clinical remission for SC maintenance regimens of ustekinumab in subjects with moderately to severely active UC induced into clinical response with ustekinumab.
- To evaluate the safety of SC maintenance regimens of ustekinumab in subjects with moderately to severely active UC induced into clinical response with ustekinumab.

Primary end point(s): Induction study:
- Number of Participants With Clinical Remission

Maintenance study:
- Number of Participants with Clinical Remission Among Participants in Clinical Response to IV Ustekinumab Induction Treatment

Secondary Outcome(s)

Secondary end point(s): Induction study:
1) Number of Participants with Clinical Response
2) Number of Participants With Endoscopic Healing
3) Mean Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score

Maintenance study:
1) Participants with Clinical Response Among Participants in Clinical Response to IV Ustekinumab Induction Treatment
2) Number of Participants with Endoscopic Healing Among Participants in Clinical Response to IV Ustekinumab Induction Treatment
3) Number of Participants with Clinical Remission and not receiving concomitant corticosteroids at Week 44
4) Number of Participants with Clinical Remission Among those who Achieved Clinical Remission at Maintenance Study Baseline

Timepoint(s) of evaluation of this end point: Induction study:
1-3) Week 8

Maintenance study:
1-4) Week 44

Secondary ID(s)

2014-005606-38-DE

CNTO1275UCO3001

Source(s) of Monetary Support

Janssen Research & Development

Ethics review

Status: Approved
Approval date: 02/11/2015
Contact: