Back to resultsEfficacy, Safety and Tolerability of AIN457 in Moderate to Severe Active Crohn's Disease
Primary Purpose
Crohn's Disease
Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
AIN457
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Crohn's Disease focused on measuring Crohn's disease, moderate, severe, active, AIN457
Eligibility 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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AIN457
Placebo
Arm Description
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
Outcomes
Primary Outcome Measures
Mean Change From Baseline in Crohns Disease Activity Index (CDAI) Score
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
Remission or response was defined as CDAI < 150 points or CDAI reduction from baseline of at least 70 points.
Percentage of Participants Achieving Remission
Remission was defined as CDAI < 150 points.
Percentage of Participants Achieving Response
Response was defined as CDAI reduction of at least 70 points from baseline.
Mean Change From Baseline in CDAI Score
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
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
Remission was defined as CDAI < 150 points.
Full Information
NCT ID
NCT00584740
First Posted
December 21, 2007
Last Updated
March 24, 2015
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00584740
Brief Title
Efficacy, Safety and Tolerability of AIN457 in Moderate to Severe Active Crohn's Disease
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated prematurely after futility criterion was met at planned interim analysis of 41 patients.
Study Start Date
August 2008 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will assess the safety and efficacy of AIN457 in patients with moderate to severe active Crohn's disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease
Keywords
Crohn's disease, moderate, severe, active, AIN457
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AIN457
Arm Type
Experimental
Arm Description
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
Intervention Type
Drug
Intervention Name(s)
AIN457
Intervention Description
10 mg/kg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo to AIN457
Primary Outcome Measure Information:
Title
Mean Change From Baseline in Crohns Disease Activity Index (CDAI) Score
Description
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.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving Remission and/or Response
Description
Remission or response was defined as CDAI < 150 points or CDAI reduction from baseline of at least 70 points.
Time Frame
6 weeks
Title
Percentage of Participants Achieving Remission
Description
Remission was defined as CDAI < 150 points.
Time Frame
6 weeks
Title
Percentage of Participants Achieving Response
Description
Response was defined as CDAI reduction of at least 70 points from baseline.
Time Frame
6 weeks
Title
Mean Change From Baseline in CDAI Score
Description
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.
Time Frame
baseline, 2 weeks, 4 weeks
Title
Area Under CDAI Curve
Description
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.
Time Frame
10 weeks
Title
Percentage of Participants Maintaining Remission
Description
Remission was defined as CDAI < 150 points.
Time Frame
10 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
NOVARTIS
Organizational Affiliation
Novartis investigator site
Official's Role
Principal Investigator
Facility Information:
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Novartis Investigative Site
City
Stuttgart
ZIP/Postal Code
70376
Country
Germany
12. IPD Sharing Statement
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Efficacy, Safety and Tolerability of AIN457 in Moderate to Severe Active Crohn's Disease
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