Trial Outcomes & Findings for Efficacy, Safety and Tolerability of AIN457 in Moderate to Severe Active Crohn's Disease (NCT NCT00584740)
NCT ID: NCT00584740
Last Updated: 2015-03-31
Results Overview
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.
TERMINATED
PHASE2
59 participants
6 weeks
2015-03-31
Participant Flow
Participant milestones
| Measure |
AIN457
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
|---|---|---|
|
Overall Study
STARTED
|
39
|
20
|
|
Overall Study
COMPLETED
|
27
|
14
|
|
Overall Study
NOT COMPLETED
|
12
|
6
|
Reasons for withdrawal
| Measure |
AIN457
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Lack of Efficacy
|
8
|
2
|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
Baseline Characteristics
Efficacy, Safety and Tolerability of AIN457 in Moderate to Severe Active Crohn's Disease
Baseline characteristics by cohort
| Measure |
AIN457
n=39 Participants
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
n=20 Participants
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.3 Years
STANDARD_DEVIATION 11.96 • n=5 Participants
|
38.3 Years
STANDARD_DEVIATION 14.29 • n=7 Participants
|
37.6 Years
STANDARD_DEVIATION 12.68 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: Safety Analysis Set: the safety set included all participants.
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.
Outcome measures
| Measure |
AIN457
n=39 Participants
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
n=20 Participants
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
|---|---|---|
|
Mean Change From Baseline in Crohns Disease Activity Index (CDAI) Score
|
-29.2 score on a scale
Standard Deviation 14.0
|
-63.1 score on a scale
Standard Deviation 13.9
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: Safety Analysis Set: the safety set included all participants.
Remission or response was defined as CDAI \< 150 points or CDAI reduction from baseline of at least 70 points.
Outcome measures
| Measure |
AIN457
n=39 Participants
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
n=20 Participants
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
|---|---|---|
|
Percentage of Participants Achieving Remission and/or Response
|
26 Percentage of participants
|
65 Percentage of participants
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: Safety Analysis Set: the safety set included all participants.
Remission was defined as CDAI \< 150 points.
Outcome measures
| Measure |
AIN457
n=39 Participants
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
n=20 Participants
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
|---|---|---|
|
Percentage of Participants Achieving Remission
|
10 Percentage of participants
|
15 Percentage of participants
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: Safety Analysis Set: the safety set included all participants.
Response was defined as CDAI reduction of at least 70 points from baseline.
Outcome measures
| Measure |
AIN457
n=39 Participants
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
n=10 Participants
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
|---|---|---|
|
Percentage of Participants Achieving Response
|
26 Percentage of participants
|
65 Percentage of participants
|
SECONDARY outcome
Timeframe: baseline, 2 weeks, 4 weeksPopulation: Safety Analysis Set: the safety set included all participants.
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.
Outcome measures
| Measure |
AIN457
n=39 Participants
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
n=20 Participants
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
|---|---|---|
|
Mean Change From Baseline in CDAI Score
Week 2
|
-15.28 score on a scale
Standard Deviation 14.010
|
-52.85 score on a scale
Standard Deviation 13.900
|
|
Mean Change From Baseline in CDAI Score
Week 4
|
-23.52 score on a scale
Standard Deviation 14.010
|
-58.48 score on a scale
Standard Deviation 13.900
|
SECONDARY outcome
Timeframe: 10 weeksPopulation: Safety Analysis Set: the safety set included all participants.
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.
Outcome measures
| Measure |
AIN457
n=39 Participants
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
n=20 Participants
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
|---|---|---|
|
Area Under CDAI Curve
|
11766.26 Units on a scale*day
Standard Error 594.54
|
9723.45 Units on a scale*day
Standard Error 784.46
|
SECONDARY outcome
Timeframe: 10 weeksPopulation: The analysis population included participants of the safety set who achieved remission.
Remission was defined as CDAI \< 150 points.
Outcome measures
| Measure |
AIN457
n=4 Participants
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
n=3 Participants
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
|---|---|---|
|
Percentage of Participants Maintaining Remission
|
100 Percentage of participants
|
67 Percentage of participants
|
Adverse Events
AIN457 Twice 10mg/kg
Placebo
Serious adverse events
| Measure |
AIN457 Twice 10mg/kg
n=39 participants at risk
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
n=20 participants at risk
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
2.6%
1/39
|
0.00%
0/20
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
2.6%
1/39
|
0.00%
0/20
|
|
Gastrointestinal disorders
Crohn's disease
|
12.8%
5/39
|
15.0%
3/20
|
|
Gastrointestinal disorders
Oesophagitis
|
2.6%
1/39
|
0.00%
0/20
|
|
General disorders
Disease progression
|
2.6%
1/39
|
0.00%
0/20
|
|
Investigations
C-reactive protein increased
|
2.6%
1/39
|
0.00%
0/20
|
Other adverse events
| Measure |
AIN457 Twice 10mg/kg
n=39 participants at risk
AIN457 10 mg/kg was given as an intravenous infusion at day 1 and day 22.
|
Placebo
n=20 participants at risk
Matching placebo to AIN457 was given as an infusion at day 1 and day 22.
|
|---|---|---|
|
Cardiac disorders
Cardiac flutter
|
0.00%
0/39
|
5.0%
1/20
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.00%
0/39
|
5.0%
1/20
|
|
Gastrointestinal disorders
Abdominal pain
|
12.8%
5/39
|
10.0%
2/20
|
|
Gastrointestinal disorders
Crohn's disease
|
7.7%
3/39
|
0.00%
0/20
|
|
Gastrointestinal disorders
Diarrhoea
|
5.1%
2/39
|
5.0%
1/20
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/39
|
5.0%
1/20
|
|
Gastrointestinal disorders
Frequent bowel movements
|
0.00%
0/39
|
5.0%
1/20
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/39
|
5.0%
1/20
|
|
Gastrointestinal disorders
Nausea
|
5.1%
2/39
|
15.0%
3/20
|
|
Gastrointestinal disorders
Vomiting
|
12.8%
5/39
|
5.0%
1/20
|
|
General disorders
Fatigue
|
5.1%
2/39
|
10.0%
2/20
|
|
General disorders
Pain
|
0.00%
0/39
|
5.0%
1/20
|
|
General disorders
Pyrexia
|
5.1%
2/39
|
5.0%
1/20
|
|
Infections and infestations
Candidiasis
|
5.1%
2/39
|
0.00%
0/20
|
|
Infections and infestations
Nasopharyngitis
|
5.1%
2/39
|
0.00%
0/20
|
|
Infections and infestations
Upper respiratory tract infection
|
7.7%
3/39
|
0.00%
0/20
|
|
Investigations
Blood pressure diastolic decreased
|
5.1%
2/39
|
0.00%
0/20
|
|
Investigations
Blood pressure increased
|
0.00%
0/39
|
5.0%
1/20
|
|
Investigations
C-reactive protein increased
|
0.00%
0/39
|
5.0%
1/20
|
|
Investigations
Electrocardiogram QT prolonged
|
5.1%
2/39
|
0.00%
0/20
|
|
Investigations
Red blood cell sedimentation rate increased
|
0.00%
0/39
|
5.0%
1/20
|
|
Metabolism and nutrition disorders
Dehydration
|
5.1%
2/39
|
0.00%
0/20
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.1%
2/39
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.3%
4/39
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.1%
2/39
|
0.00%
0/20
|
|
Nervous system disorders
Dizziness
|
2.6%
1/39
|
5.0%
1/20
|
|
Nervous system disorders
Headache
|
7.7%
3/39
|
15.0%
3/20
|
|
Nervous system disorders
Lethargy
|
0.00%
0/39
|
5.0%
1/20
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/39
|
5.0%
1/20
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/39
|
10.0%
2/20
|
|
Reproductive system and breast disorders
Prostatitis
|
0.00%
0/39
|
5.0%
1/20
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/39
|
5.0%
1/20
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
2.6%
1/39
|
5.0%
1/20
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.6%
1/39
|
5.0%
1/20
|
|
Vascular disorders
Hot flush
|
0.00%
0/39
|
5.0%
1/20
|
|
Vascular disorders
Hypertension
|
0.00%
0/39
|
5.0%
1/20
|
Additional Information
Study Director
Novartis
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER