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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00584740

Enrollment

Registered

2008-01-02

Start date

2008-08-31

Completion date

2010-08-31

Last updated

2015-03-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Crohn's Disease

Keywords

Crohn's disease, moderate, severe, active, AIN457

Brief summary

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

Interventions

DRUGAIN457

10 mg/kg

DRUGPlacebo

Matching placebo to AIN457

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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/

Design outcomes

Primary

Measure	Time frame	Description
Mean Change From Baseline in Crohns Disease Activity Index (CDAI) Score	6 weeks	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

Measure	Time frame	Description
Percentage of Participants Achieving Remission	6 weeks	Remission was defined as CDAI \< 150 points.
Percentage of Participants Achieving Response	6 weeks	Response was defined as CDAI reduction of at least 70 points from baseline.
Percentage of Participants Achieving Remission and/or Response	6 weeks	Remission or response was defined as CDAI \< 150 points or CDAI reduction from baseline of at least 70 points.
Area Under CDAI Curve	10 weeks	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	10 weeks	Remission was defined as CDAI \< 150 points.
Mean Change From Baseline in CDAI Score	baseline, 2 weeks, 4 weeks	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.

Countries

Germany

Participant flow

Participants by arm

Arm	Count
AIN457 AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.	39
Placebo Matching placebo to AIN457 was given as an infusion at day 1 and day 22.	20
Total	59

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	1
Overall Study	Lack of Efficacy	8	2
Overall Study	Lost to Follow-up	0	1
Overall Study	Withdrawal by Subject	3	2

Baseline characteristics

Characteristic	AIN457	Placebo	Total
Age, Continuous	37.3 Years STANDARD_DEVIATION 11.96	38.3 Years STANDARD_DEVIATION 14.29	37.6 Years STANDARD_DEVIATION 12.68
Sex: Female, Male Female	15 Participants	9 Participants	24 Participants
Sex: Female, Male Male	24 Participants	11 Participants	35 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	22 / 39	9 / 20
serious Total, serious adverse events	7 / 39	3 / 20

Outcome results

Primary

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.

Time frame: 6 weeks