Efficacy, Safety and Tolerability of AIN457 in Moderate to Severe Active Crohn's Disease

This study has been terminated.
(The study was terminated prematurely after futility criterion was met at planned interim analysis of 41 patients.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00584740
First received: December 21, 2007
Last updated: March 24, 2015
Last verified: March 2015
  Purpose

This study will assess the safety and efficacy of AIN457 in patients with moderate to severe active Crohn's disease.


Condition Intervention Phase
Crohn's Disease
Drug: AIN457
Drug: Placebo
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 Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Proof-of-concept Study to Assess the Efficacy, Safety and Tolerability of Two Single iv Infusions of AIN457 10 mg/kg (Anti IL-17 Monoclonal Antibody) in Patients With Moderate to Severe Active Crohn's Disease

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Mean Change From Baseline in Crohns Disease Activity Index (CDAI) Score [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The Crohns Disease Activity Index or CDAI is a research tool used to quantify the symptoms of patients with Crohns disease. Participants were asked to record on a paper diary the frequency of stools, abdominal pain and general well-being on a daily basis. In addition to the diary data, the investigator assessed the following for the calculation of CDAI score: arthritis/arthralgia, iritis/uveitis, erythema nodosum/pyoderma gangrenousum/aphthous stomatitis, anal fissure/fistula/abscess, other fistula; fever; use of antidiarrheal; abdominal mass; hematocrit; body weight. The CDAI score is the sum of the products of each item multiplied by its weighting factor. CDAI ranges from 0 to >=600, where remission of Crohn's disease is defined as CDAI < 150, and severe disease is defined as CDAI > 450. A negative change in mean score indicates improvement.


Secondary Outcome Measures:
  • Percentage of Participants Achieving Remission and/or Response [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Remission or response was defined as CDAI < 150 points or CDAI reduction from baseline of at least 70 points.

  • Percentage of Participants Achieving Remission [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Remission was defined as CDAI < 150 points.

  • Percentage of Participants Achieving Response [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Response was defined as CDAI reduction of at least 70 points from baseline.

  • Mean Change From Baseline in CDAI Score [ Time Frame: baseline, 2 weeks, 4 weeks ] [ Designated as safety issue: No ]
    The Crohns Disease Activity Index or CDAI is a research tool used to quantify the symptoms of patients with Crohns disease. Participants were asked to record on a paper diary the frequency of stools, abdominal pain and general well-being on a daily basis. In addition to the diary data, the investigator assessed the following for the calculation of CDAI score: arthritis/arthralgia, iritis/uveitis, erythema nodosum/pyoderma gangrenousum/aphthous stomatitis, anal fissure/fistula/abscess, other fistula; fever; use of antidiarrheal; abdominal mass; hematocrit; body weight. The CDAI score is the sum of the products of each item multiplied by its weighting factor. CDAI ranges from 0 to >=600, where remission of Crohn's disease is defined as CDAI < 150, and severe disease is defined as CDAI > 450. A negative change in mean score indicates improvement.

  • Area Under CDAI Curve [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    The Crohns Disease Activity Index or CDAI is a research tool used to quantify the symptoms of patients with Crohns disease. Participants were asked to record on a paper diary the frequency of stools, abdominal pain and general well-being on a daily basis. In addition to the diary data, the investigator assessed the following for the calculation of CDAI score: arthritis/arthralgia, iritis/uveitis, erythema nodosum/pyoderma gangrenousum/aphthous stomatitis, anal fissure/fistula/abscess, other fistula; fever; use of antidiarrheal; abdominal mass; hematocrit; body weight. The CDAI score is the sum of the products of each item multiplied by its weighting factor. CDAI ranges from 0 to >=600, where remission of Crohn's disease is defined as CDAI < 150, and severe disease is defined as CDAI > 450. An area under the CDAI response curve analysis was performed with a starting point from week 4.

  • Percentage of Participants Maintaining Remission [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    Remission was defined as CDAI < 150 points.


Enrollment: 59
Study Start Date: August 2008
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AIN457
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
Drug: AIN457
10 mg/kg
Placebo Comparator: Placebo
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
Drug: Placebo
Matching placebo to AIN457

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female; 18-75 years old
  • Diagnosis of Crohn's disease for at least 3 months prior to screening
  • Confirmation of Crohn's disease by endoscopic or imaging examination
  • Moderately active Crohn's disease at baseline, defined as:
  • CDAI ≥220 and ≤450
  • Active disease despite prior treatment with corticosteroids for at least 2 weeks, or immunosuppressants for at least 3 months. Treatment with azathioprine, 6-MP or MTX is allowed but must have been on a stable dose for at least 10 weeks, corticosteroids are allowed but must have been on a stable doses of prednisolone not exceeding 40 mg for two weeks prior to baseline. Immunosuppressants other than those listed above, such as cyclosporine, tacrolimus and mycophenolate, are not allowed and must be stopped (wash-out periods defined in the protocol);

Exclusion Criteria:

  • Body Mass Index >34
  • Positive PPD tuberculin skin test or QuantiFeron test
  • Any subject with evidence of active pulmonary disease or evidence of latent tuberculosis or fungal infection at screening or within past 3 months
  • Symptoms associated with active bowel structuring disease and pre-stenotic dilation on radiographs
  • Fistulizing disease if complicated by sepsis and/or untreated abscess
  • Multiple bowel surgeries and clinically important short bowel syndrome defined as an inability to maintain caloric intake
  • Use of certain medications as specified in the protocol
  • Clinical improvement due to other Crohn's therapy

Other protocol-defined inclusion/exclusion criteria may apply

  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: NCT00584740

Locations
Germany
Novartis Investigative Site
Berlin, Germany, 10117
Novartis Investigative Site
Stuttgart, Germany, 70376
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Principal Investigator: NOVARTIS Novartis investigator site
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00584740     History of Changes
Other Study ID Numbers: CAIN457A2202
Study First Received: December 21, 2007
Results First Received: January 28, 2015
Last Updated: March 24, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Novartis:
Crohn's disease, moderate, severe, active, AIN457

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

ClinicalTrials.gov processed this record on July 01, 2015