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

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

Official Title
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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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: AIN457
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AIN457<br>AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22. | Drug: AIN457<br>* 10 mg/kg<br>|
| Placebo Comparator: Placebo<br>Matching placebo to AIN457 was given as an infusion at day 1 and day 22. | Drug: Placebo<br>* Matching placebo to AIN457<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's disease, moderate, severe, active, AIN457