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

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

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

Study Overview

• Status: Terminated
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Placebo; Drug: AIN457

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Stuttgart, Germany, 70376
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 weeks
Percentage of Participants Achieving Remission	Remission was defined as CDAI < 150 points.	6 weeks
Percentage of Participants Achieving Response	Response was defined as CDAI reduction of at least 70 points from baseline.	6 weeks
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.	baseline, 2 weeks, 4 weeks
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.	10 weeks
Percentage of Participants Maintaining Remission	Remission was defined as CDAI < 150 points.	10 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: December 21, 2007
• First Submitted That Met QC Criteria: December 21, 2007
• First Posted (Estimate): January 2, 2008

Study Record Updates

• Last Update Posted (Estimate): March 31, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Crohn's disease, moderate, severe, active, AIN457
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: CAIN457A2202