A Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Patients with Moderately to Severely Active Crohn’s Disease

• Register: EUCTR
• Last refreshed on: 5 March 2018
• Main ID: EUCTR2010-022760-12-DE
• Date of registration: 26/05/2011
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: A Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Patients with Moderately to Severely Active Crohn’s Disease
• Scientific title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Subjects with Moderately to Severely Active Crohn’s Disease - IMUNITI
• Date of first enrolment: 13/09/2011
• Target sample size: 1310
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022760-12
• 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: 3
• 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, Brazil, Bulgaria, Canada, Croatia, Czech Republic, Denmark, European Union, Germany, Hungary, Iceland, Ireland, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Russian Federation, Serbia, South Africa, Spain, United Kingdom, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion criteria

Inclusion criteria:
1. Have received study agent at Week 0 in study CNTO1275CRD3001 or CNTO1275CRD3002 and completed the Week 8 CDAI score evaluation.

2. Be able to complete the Week 0 visit in study CNTO1275CRD3003 within 4 days of the Week 8 visit in study CNTO1275CRD3001 or CNTO1275CRD3002. At the discretion of the investigator, the window may be extended to 8 days to allow appropriate treatment and/or recovery of nonserious infections (eg, acute upper respiratory tract infection, simple urinary tract infection).

3. Be able and willing to adhere to the study visit schedule and comply with other protocol requirements

4. Be capable of providing informed consent, which must be obtained prior to any study-related procedures
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 1235
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion criteria:
1. Had any of the following changes to their concomitant medications due to Crohn’s disease (ie, lack of efficacy) since Week 0 of studies CNTO1275CRD3001 and CNTO1275CRD3002
a. Increase in physician-prescribed daily dose of oral corticosteroids of more than 5 mg or more of prednisone (or equivalent increase in prednisone-equivalent dose of other corticosteroids),
b. Initiation of oral budesonide or increase in daily dose
c. Initiation of parenteral, and oral corticosteroids for Crohn’s disease, except for dose equivalent substitutions among oral corticosteroids
d. Initiation or increased physician-prescribed daily dose of methotrexate (MTX), 6-MP, or azathioprine (AZA), except for dose equivalent substitutions

2. Initiated a protocol prohibited medication since Week 0 of studies CNTO1275CRD3001 and CNTO1275CRD3002:
a. Immune suppressing immunomodulatory agents other than 6-MP/AZA or MTX (including but not limited to 6-TG, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil)
b. Immunosuppressant biologic agents (including but not limited to TNF-antagonists, natalizumab, abatacept, commercial ustekinumab)
c. Experimental Crohn’s disease medications (including but not limited to thalidomide, briakinumab, vedolizumab, traficet, AMG-827)

3. Underwent a Crohn’s disease related surgery since Week 0 of induction study CNTO1275CRD3001 or CNTO1275CRD3002. Seton placement and recent cutaneous and perianal abscesses which have been drained and adequately treated at least 3 weeks prior to receiving baseline study agent are not exclusionary provided that there is no anticipated need for any further surgery

4. Subjects from countries with high multidrug-resistant TB burden (eg, South Africa, Bulgaria, and the Russian Federation) diagnosed with latent TB during induction study CNTO1275CRD3001 or CNTO1275CRD3002, or any subject who has discontinued or is noncompliant with appropriate therapy for the treatment of latent TB.

5. Are diagnosed with any medical condition (or signs or symptoms thereof) which would have precluded enrollment in induction studies CNTO1275CRD3001 and CNTO1275CRD3002. This includes any lymphoproliferative disorder or malignancy (other than basal cell carcinoma of the skin), opportunistic or other significant infection, or other severe, progressive, or uncontrolled medical (eg renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurologic, or autoimmune) or psychiatric disease, including recent significant instability in a previous condition.

6. Have signs and symptoms of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis.

7. Is a woman who is pregnant, or breast-feeding, or planning to become pregnant or is a man who plans to father a child while enrolled in this study or within 20 weeks after the last dose of study agent.


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

Health Condition(s) or Problem(s) studied

Moderately to severely active Crohn's disease
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

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

Intervention(s)

Trade Name: Stelara
Product Name: Ustekinumab
Product Code: CNTO1275
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Ustekinumab
CAS Number: 815610-63-0
Current Sponsor code: CNTO1275
Other descriptive name: N/A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 90-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Product Name: Ustekinumab
Product Code: CNTO1275
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Ustekinumab
CAS Number: 815610-63-0
Current Sponsor code: CNTO1275
Other descriptive name: N/A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 77-104
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The primary objectives are:
- To evaluate clinical remission for the 2 SC maintenance regimens of ustekinumab in subjects with moderately to severely active Crohn’s disease induced into clinical response with ustekinumab in the induction studies, CNTO1275CRD3001 and CNTO1275CRD3002.
- To evaluate the safety of 2 SC maintenance regimens of ustekinumab in subjects with moderately to severely active Crohn’s disease.

Timepoint(s) of evaluation of this end point: At week 44

Secondary Objective: The secondary objectives are:
- To evaluate the efficacy of ustekinumab in maintaining clinical response in subjects induced into clinical response.
- To evaluate the efficacy of ustekinumab in maintaining clinical remission in subjects induced into clinical remission.
- To evaluate the efficacy of ustekinumab in achieving corticosteroid free remission. To evaluate the pharmacokinetics, immunogenicity, and pharmacodynamics of Ustekinumab therapy, including changes in C-reactive protein (CRP), fecal calprotectin, fecal lactoferrin, and other pharmacodynamic biomarkers.
- To evaluate the effect of ustekinumab on health related quality of life.

Primary end point(s): The primary endpoint analysis and the major secondary endpoint analyses will include only subjects in clinical response to ustekinumab at Week 8 from 1 of the induction studies (CNTO1275CRD3001 or CNTO1275CRD3002) who were randomized at Week 0 of this study into 1 of the maintenance regimens.

The primary endpoint is clinical remission at Week 44, where clinical remission is defined as a CDAI score of < 150 points.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: At week 44

Secondary end point(s): The major secondary endpoints in order of importance are:
1. Clinical response at Week 44.
2. Clinical remission at Week 44 among subjects in clinical remission to ustekinumab at Week 0.
3. Corticosteroid-free remission at Week 44.
4. Clinical remission at Week 44 in the subset of subjects who were refractory or intolerant to TNF-antagonist therapy (ie, subjects from induction study CNTO1275CRD3001).

Secondary ID(s)

CNTO1275CRD3003

Source(s) of Monetary Support

Janssen R&D