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A Study of Safety and Effectiveness of Ustekinumab in Patients With Moderate to Severe Active Crohn's Disease Who Have Been Previously Treated With Anti-TNF Therapy

This study has been completed.
Sponsor:
Information provided by:
Centocor, Inc.
ClinicalTrials.gov Identifier:
NCT00771667
First received: October 10, 2008
Last updated: March 26, 2013
Last verified: March 2013
  Purpose

A medical research study in adult patients who have moderate to severe Crohn's disease designed to determine whether or not treatment with an experimental drug called ustekinumab (or CNTO1275) is safe or not and to determine if the treatment will reduce the symptoms of Crohn's disease.


Condition Intervention Phase
Crohn's Disease
Drug: Placebo (IP)
Drug: Ustekinumab 1mg/kg (IP)
Drug: Ustekinumab 3 mg/kg (IP)
Drug: Ustekinumab 6 mg/kg (IP)
Drug: Placebo IV - Responder - Placebo SC (MP)
Drug: Placebo IV - Nonresponder - Ustekinumab 270/90 mg SC (MP)
Drug: Ustekinumab IV - Responder - Placebo SC (MP)
Drug: Ustekinumab IV - Responder - Ustekinumab 90mg SC (MP)
Drug: Ustekinumab IV - Nonresponder - Placebo SC (MP)
Drug: Ustekinumab IV - Nonresponder - Ustekinumab 90mg SC (MP)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Ustekinumab Therapy in Subjects With Moderately to Severely Active Crohn's Disease Previously Treated With TNF Antagonist Therapy

Resource links provided by NLM:


Further study details as provided by Centocor, Inc.:

Primary Outcome Measures:
  • Number of Participants With Clinical Response at Week 6 [ Time Frame: Baseline to Week 6 ] [ Designated as safety issue: No ]
    As measured by the Crohn's Disease Activity Index (CDAI). CDAI scores range from 0 points (minimal disease activity) to over 600 points (severe disease activity). Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of < 150 was attained.


Secondary Outcome Measures:
  • Number of Participants With Clinical Remission at Week 6 [ Time Frame: Baseline to Week 6 ] [ Designated as safety issue: No ]
    As measured by a CDAI score of < 150 points.

  • Number of Participants With Clinical Response at Week 4 [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    As measured by the CDAI. Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of < 150 was attained.

  • Number of Participants With Clinical Response at Week 8 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
    As measured by the CDAI. Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of < 150 was attained.

  • Number of Participants With Clinical Remission at Week 8 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
    As measured by a CDAI score of < 150 points.

  • Number of Participants With Clinical Remission at Week 22 (Among Responders From Week 6) [ Time Frame: Baseline to Week 22 ] [ Designated as safety issue: No ]
    As measured by a CDAI score of < 150 points.

  • Number of Participants With Clinical Response at Week 22 (Among Responders From Week 6) [ Time Frame: Baseline to Week 22 ] [ Designated as safety issue: No ]
    As measured by the CDAI. Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of < 150 was attained.


Enrollment: 526
Study Start Date: December 2008
Study Completion Date: December 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo (IP) Drug: Placebo (IP)
Induction phase (Week 0-8) (IP) - Placebo IV group
Experimental: Ustekinumab 1mg/kg (IP) Drug: Ustekinumab 1mg/kg (IP)
Induction phase (Week 0-8) (IP) - Ustekinumab 1 mg/kg IV group
Experimental: Ustekinumab 3 mg/kg (IP) Drug: Ustekinumab 3 mg/kg (IP)
Induction phase (Week 0-8) (IP) - Ustekinumab 3mg/kg IV group
Experimental: Ustekinumab 6 mg/kg (IP) Drug: Ustekinumab 6 mg/kg (IP)
Induction phase (Week 0-8) (IP) - Ustekinumab 6mg/kg IV group
Placebo Comparator: Placebo IV - Responder - Placebo SC (MP) Drug: Placebo IV - Responder - Placebo SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Placebo IV at Week 0 - Responder at week 6 - Receiving Placebo SC at Week 8 and Week 16
Placebo Comparator: Placebo IV - Nonresponder - Ustekinumab 270/90 mg SC Drug: Placebo IV - Nonresponder - Ustekinumab 270/90 mg SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Placebo IV at Week 0 - Nonresponder at week 6 - Receiving Ustekinumab 270 mg SC at Week 8 and 90 mg at Week 16
Placebo Comparator: Ustekinumab IV - Responder - Placebo SC (MP) Drug: Ustekinumab IV - Responder - Placebo SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Responder at week 6 - Receiving Placebo SC at Week 8 and Week 16
Experimental: Ustekinumab IV - Responder - Ustekinumab 90mg SC (MP) Drug: Ustekinumab IV - Responder - Ustekinumab 90mg SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Responder at week 6 - Receiving Ustekinumab 90 mg SC at Week 8 and Week 16
Placebo Comparator: Ustekinumab IV - Nonresponder - Placebo SC (MP) Drug: Ustekinumab IV - Nonresponder - Placebo SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Nonresponder at week 6 - Receiving Placebo SC at Week 8 and Week 16
Experimental: Ustekinumab IV - Nonresponder - Ustekinumab 90mg SC (MP) Drug: Ustekinumab IV - Nonresponder - Ustekinumab 90mg SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Nonresponder at week 6 - Receiving Ustekinumab 90 mg SC at Week 8 and Week 16

Detailed Description:

In Crohn's disease there is inflammation (changes in body tissue which normally happen during injury or infection) and or ulceration (open sores) in the intestines.This occurs because the immune system (the part of the body that fights off infection) has an abnormal and overactive response against the intestine and bowel tissues of the body. Crohn's disease is usually treated with medications that either directly decrease inflammation or decrease the general activity of the immune system to improve the diarrhea, abdominal pain, and other symptoms of Crohn's Disease. Ustekinumab antibodies (natural substances made by your immune system to stick to and help remove foreign materials in your body that cause diseases) have been created to stick to and block the activity of two of the immune substances thought to cause abnormal inflammation of Crohn's disease. Patients who are eligible and who have received Remicade, Humira, or Cimzia and failed or been intolerant to one of these drugs will be randomized to either active drug (ustekinumab) or placebo. All patients will be randomized (like flipping a coin) at week 0 to be in one of 4 groups. At week 0 the study drug will be given by IV administration and at weeks 8 and 16 by subcutaneous injection. There will be 11 study visits in total and the study will continue until week 36. Blood and stool samples will be collected and studied, questionnaires to check on how you are doing in terms of your disease will be completed, an Electrocardiogram (EKG) obtained, safety evaluations conducted and diary cards distributed to be completed during the entire study. One of 4 groups: Grp 1-placebo, Grp 2-active drug 1mg/kg IV, Grp 3-active drug 3mg/kg IV, Grp 4-active drug 6mg/kg IV. Based on the clinical response status at Week 6, patients from Grps 2, 3 and 4 will be re-randomized at week 8 to receive either placebo or 90 mg SC at both weeks 8 and 16 and patients from Grp 1 will receive placebo at Week 8 and Week 16 or a 270 mg SC injection at Week 8 and 90 mg SC at Week 16.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have Crohn's disease or fistulizing Crohn's disease of at least 3 months duration
  • Must have received Remicade, adalimumab or Cimzia at a dose approved for the treatment of Crohn's disease
  • Must have failed or been intolerant to Remicade, Humira or Cimzia for treatment of Crohn's disease
  • Must be 18 years of age or older
  • Must have active Crohn's disease according to the Crohn's Disease Activity Index (CDAI > =220 and < =450).

Exclusion Criteria:

  • Patients who have had any kind of bowel resection, diversions or placement of a stoma within 6 months
  • Are pregnant, nursing or planning pregnancy (both men and women) while enrolled in the study or within 1 year after receiving study agent
  • Patients who have received Remicade, Humira or Cimzia < =8 weeks before the first administration of study drug
  • Patients with certain complications of Crohn's disease that would make it hard to assess response to study drug
  • Patients with a history of or ongoing chronic or recurrent infectious disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00771667

  Show 178 Study Locations
Sponsors and Collaborators
Centocor, Inc.
Investigators
Study Director: Centocor, Inc. Clinical Trial Centocor, Inc.
  More Information

No publications provided by Centocor, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Director, Clinical Research, Janssen R&D US
ClinicalTrials.gov Identifier: NCT00771667     History of Changes
Other Study ID Numbers: CR015238, C0743T26
Study First Received: October 10, 2008
Results First Received: October 10, 2011
Last Updated: March 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Centocor, Inc.:
Interleukin-12
Inflammation
Research study
Ustekinumab
CNTO1275
Interleukin-23

Additional relevant MeSH terms:
Crohn Disease
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on November 25, 2014