Trial Outcomes & Findings for Double Blind, Placebo Controlled Study to Assess Efficacy of AIN457 in Moderate to Severe Ankylosing Spondylitis (NCT NCT00809159)
NCT ID: NCT00809159
Last Updated: 2015-12-09
Results Overview
Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of 20% or more and absolute improvement of at least 1 units (on a scale of 0 \[least\] to 10 \[worst\]) from Baseline in at least 3 of the following 4 domains, with absence of deterioration (worsening of at least 20% an absolute Worsening of at least 1 unit) in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores
COMPLETED
PHASE2
60 participants
6 Weeks
2015-12-09
Participant Flow
Part 1 of the study, patients received 2 infusions spaced three weeks apart of 10 mg/kg AIN457 or placebo, and in Part 2 of the study, patients received 2 infusions spaced three weeks apart of 0.1 mg/kg, 1.0 mg/kg or 10 mg/kg AIN457, respectively.
Part 1 participants were randomized 4:1 to receive AIN457A or placebo. Part 2, the randomization ratio was to be 2:2:1 for the three dose groups, 0.1 mg/kg, 1 mg/kg and 10 mg/kg. More subjects were randomized to the 0.1 and 1mg/kg dose groups as compared to the 10 mg/kg group, as 24 subjects were already randomized to the 10 mg/kg group in Part 1.
Participant milestones
| Measure |
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
Parts 1 and 2 - AIN457A 10 mg/kg
AIN457A 10 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 and 2 - AIN457 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|---|---|
|
Part 1
STARTED
|
24
|
6
|
0
|
0
|
0
|
0
|
|
Part 1
PK Analysis Set
|
24
|
6
|
0
|
0
|
0
|
0
|
|
Part 1
PD Analysis Set
|
23
|
6
|
0
|
0
|
0
|
0
|
|
Part 1
COMPLETED
|
16
|
3
|
0
|
0
|
0
|
0
|
|
Part 1
NOT COMPLETED
|
8
|
3
|
0
|
0
|
0
|
0
|
|
Part 1 and 2
STARTED
|
0
|
0
|
30
|
12
|
12
|
6
|
|
Part 1 and 2
PK Analysis Set
|
0
|
0
|
30
|
12
|
12
|
6
|
|
Part 1 and 2
PD Analysis Set
|
0
|
0
|
28
|
12
|
12
|
6
|
|
Part 1 and 2
COMPLETED
|
0
|
0
|
20
|
7
|
6
|
3
|
|
Part 1 and 2
NOT COMPLETED
|
0
|
0
|
10
|
5
|
6
|
3
|
Reasons for withdrawal
| Measure |
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
Parts 1 and 2 - AIN457A 10 mg/kg
AIN457A 10 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 and 2 - AIN457 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|---|---|
|
Part 1
Adverse Event
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Part 1
Lost to Follow-up
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Part 1
Withdrawal by Subject
|
3
|
1
|
0
|
0
|
0
|
0
|
|
Part 1
Unsatisfactory therapeutic effect
|
3
|
1
|
0
|
0
|
0
|
0
|
|
Part 1 and 2
Unsatisfactory therapeutic effect
|
0
|
0
|
4
|
3
|
5
|
1
|
|
Part 1 and 2
Administrative problems
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Part 1 and 2
Adverse Event
|
0
|
0
|
1
|
0
|
1
|
1
|
|
Part 1 and 2
Lost to Follow-up
|
0
|
0
|
1
|
1
|
0
|
0
|
|
Part 1 and 2
Withdrawal by Subject
|
0
|
0
|
4
|
0
|
0
|
1
|
Baseline Characteristics
Double Blind, Placebo Controlled Study to Assess Efficacy of AIN457 in Moderate to Severe Ankylosing Spondylitis
Baseline characteristics by cohort
| Measure |
Parts 1 and 2 - AIN457A 10 mg/kg
n=30 Participants
AIN457A 10 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 and 2 - AIN457 1.0 mg/kg
n=12 Participants
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=12 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
40.7 Years
STANDARD_DEVIATION 9.69 • n=5 Participants
|
47.2 Years
STANDARD_DEVIATION 10.50 • n=7 Participants
|
42.8 Years
STANDARD_DEVIATION 9.17 • n=5 Participants
|
45.0 Years
STANDARD_DEVIATION 9.96 • n=4 Participants
|
42.8 Years
STANDARD_DEVIATION 9.88 • n=21 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
38 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 6 WeeksPopulation: Pharmacodynamic Analysis set: All patients with a least one evaluable post-treatment PD measurement and no major protocol deviations with impact on PD data were included. One subjects was excluded from the PD set in the AIN457 10mg/kg Part 1 due to protocol deviation
Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of 20% or more and absolute improvement of at least 1 units (on a scale of 0 \[least\] to 10 \[worst\]) from Baseline in at least 3 of the following 4 domains, with absence of deterioration (worsening of at least 20% an absolute Worsening of at least 1 unit) in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=23 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Percentage of Participants Who Achieved ASAS20 Response
|
59.2 Percentage
|
24.5 Percentage
|
—
|
—
|
PRIMARY outcome
Timeframe: 6 WeeksPopulation: Pharmacodynamic Analysis set: All patients with a least one evaluable post-treatment PD measurement and no major protocol deviations with impact on PD data were included. One subjects was excluded from the PD set in the AIN457 10mg/kg Part 2 due to the absence of available post-baseline PD measurements
ASAS20 as described in Primary Outcome. ASAS40 responder had improvement of 40% or more and absolute improvement of at least 2 units (on a scale of 0 \[least\] to 10 \[worst\]) from Baseline in at least 3 of the following 4 domains, with no deterioration in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores). ASAS 5/6 responder had improvement of 20% or more) from Baseline in at least 5 of the following 6 domains: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (BASFI); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores); Spinal Mobility (BASFI); Acute phase reactant (CRP)
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=26 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=11 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=11 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
n=3 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score From Baseline to 6 Weeks After First Infusion in Part 2
|
-1.87 Units on a scale
Interval -2.691 to -1.051
|
-2.0151 Units on a scale
Interval -3.275 to -0.755
|
-1.2002 Units on a scale
Interval -2.514 to 0.113
|
-1.0577 Units on a scale
Interval -2.893 to 0.777
|
SECONDARY outcome
Timeframe: Day8,15,29,week 6, 8, 10, 12, 16, 20, 24, 28Population: Pharmacodynamic Analysis set: All patients with a least one evaluable post-treatment PD measurement and no major protocol deviations with impact on PD data were included. One subjects was excluded from the PD set in the AIN457 10mg/kg Part 1 due to protocol deviation
ASAS20 responder had improvement of 40% or more and absolute improvement of at least 2 units (scale of 0 \[least\] to 10 \[worst\]) from Baseline in at least 3 of the following 4 domains, with no deterioration in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores). ASAS 5/6 responder had improvement of 20% or more) from Baseline in at least 5 of the following 6 domains: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores); Spinal Mobility (BASFI); Acute phase reactant (CRP)
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=23 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS20 at Day 8
|
9 Participants
|
2 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS20 at Day 15
|
9 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS20 at Day 29
|
11 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS40 at Day 8
|
4 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS40 at Day 15
|
4 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS 5/6 at Day 15
|
5 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS 5/6 at Day 29
|
8 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS20 at week 6
|
14 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS20 at week 28
|
7 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS40 at week 10
|
5 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS40 at week 16
|
3 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS40 at week 20
|
2 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS40 at week 24
|
3 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS40 at week 28
|
2 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS 5/6 at week 6
|
8 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS 5/6 at week 8
|
7 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS 5/6 at week 12
|
3 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS 5/6 at week 20
|
2 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS 5/6 at week 28
|
1 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS40 at Day 29
|
8 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS 5/6 at Day 8
|
5 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS20 at week 8
|
8 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS20 at week 10
|
9 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS20 at week 12
|
9 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS20 at week 16
|
8 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS20 at week 20
|
6 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS20 at week 24
|
7 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS40 at week 6
|
7 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS40 at week 8
|
5 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS40 at week 12
|
3 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS 5/6 at week 10
|
6 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS 5/6 at week 16
|
4 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
ASAS 5/6 at week 24
|
3 Participants
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 8,15,29,week 6, 8, 10, 12, 16, 20, 24, 28Population: Pharmacodynamic Analysis set: All patients with a least one evaluable post-treatment PD measurement and no major protocol deviations with impact on PD data were included. One subjects was excluded from the PD set in the AIN457 10mg/kg Part 2 due to the absence of available post-baseline PD measurements
a Bayesian model was fitted to the ASAS20 , ASAS40 and ASAS 5/6 response rates on active and placebo treatments. A Bayesian analysis had been chosen to allow the direct incorporation into the analysis of information about placebo response rates from historical data
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=28 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=12 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=12 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS20 at day 8 (n=28,12,12,6)
|
12 Participants
|
3 Participants
|
6 Participants
|
2 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS20 at day 15 (n=28,12,12,5)
|
11 Participants
|
7 Participants
|
4 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS20 at day 29 (n=28,12,11,6)
|
14 Participants
|
6 Participants
|
4 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS40 at day 8 (n=28,12,12,6)
|
6 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS40 at day 29 (28,12,11,6)
|
10 Participants
|
3 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS 5/6 at day 8 (28,12,12,6)
|
6 Participants
|
3 Participants
|
5 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS 5/6 at day 29 (n=28,12,11,6)
|
9 Participants
|
5 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS20 at week 6 (n=27,11,11,6)
|
16 Participants
|
4 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS20 at week 10 (n=27,11,10,6)
|
11 Participants
|
5 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS20 at week 12 (n=27,12,11,6)
|
12 Participants
|
3 Participants
|
4 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS20 at week 16 (n=28,12,11,6)
|
9 Participants
|
5 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS20 at week 20 (n=28,12,11,6)
|
6 Participants
|
4 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS40 at week 10 (28,11,11,6)
|
5 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS40 at week 16 (n=28,12,11,6)
|
3 Participants
|
3 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS40 at week 24 (n=28,12,11,6)
|
3 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS40 at week 28 (n=28,11,11,6)
|
3 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS 5/6 at week 10 (n=27,11,10,6)
|
6 Participants
|
4 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS 5/6 at week 28 (n=28,11,10,6)
|
2 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS40 at day 15 (n=28,12,12,5)
|
5 Participants
|
3 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS 5/6 at day 15 (n=28,12,12,5)
|
5 Participants
|
5 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS20 at week 8 (n=28,11,11,6)
|
10 Participants
|
4 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS20 at week 24 (n=28,12,11,6)
|
7 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS20 at week 28 (n=28,11,11,6)
|
8 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS40 at week 6 (n=27,11,11,6)
|
8 Participants
|
2 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS40 at week 8 (n=28,11,11,6)
|
5 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS40 at week 12 (n=27,12,11,6)
|
3 Participants
|
2 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS40 at week 20 (n=28,12,11,6)
|
2 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS 5/6 at week 6 (n=28,11,11,6)
|
9 Participants
|
3 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS 5/6 at week 8 (n=28,11,11,6)
|
7 Participants
|
4 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS 5/6 at week 12 (n=28,12,11,6)
|
5 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS 5/6 at week 16 (n=28,12,11,6)
|
5 Participants
|
5 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS 5/6 at week 20 (n=28,12,11,6)
|
2 Participants
|
3 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
ASAS 5/6 at week 24 (n=28,12,11,6)
|
3 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, week 6, week 28Population: Pharmacodynamic Analysis set: All patients with a least one evaluable post-treatment PD measurement and no major protocol deviations with impact on PD data were included. One subjects was excluded from the PD set in the AIN457 10mg/kg Part 1 due to protocol deviation
The study used MRI with fat-saturating techniques such as short tau inversion recovery (STIR) to look for the presence of bone marrow edema. The Berlin modification of ASspiMRI-a (ASspiMRI-a) scoring technique assesses inflammation in each of the 23 disc vertebral units (DVU), capturing edema and erosion. Scores for each DVU range from 0-3 (0=normal; 1=minor bone marrow edema (less than25% of DVU; 3=severe bone marrow edema (more that 50% of DVU). The composite score ranges from 0 to 69, with higher scores indicating more severe inflammation
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=22 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=5 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Magnetic Resonance Imaging (MRI) Inflammatory Scores at Baseline, Week 6 in Part 1
Baseline (n=22,5)
|
9.2 Score
Standard Deviation 8.87
|
20.6 Score
Standard Deviation 20.18
|
—
|
—
|
|
Magnetic Resonance Imaging (MRI) Inflammatory Scores at Baseline, Week 6 in Part 1
Week 28 (n=16,5)
|
5.7 Score
Standard Deviation 6.20
|
19.0 Score
Standard Deviation 19.33
|
—
|
—
|
|
Magnetic Resonance Imaging (MRI) Inflammatory Scores at Baseline, Week 6 in Part 1
Week 6 (n=22,3)
|
6.6 Score
Standard Deviation 6.56
|
21.0 Score
Standard Deviation 24.56
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded.
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28.
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=23 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1
|
21.07 Days
Interval 0.083 to 21.9
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded.
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28.
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=28 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=12 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=12 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 and 2
|
21.08 Days
Interval 0.083 to 22.2
|
21.08 Days
Interval 0.125 to 23.0
|
21.12 Days
Interval 19.1 to 22.1
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=23 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1
|
357.7 ug/mL
Standard Deviation 87.74
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=28 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=12 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=12 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 and 2
|
363.9 ug/mL
Standard Deviation 82.30
|
33.13 ug/mL
Standard Deviation 9.828
|
5.509 ug/mL
Standard Deviation 5.418
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=20 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1
AUCinf
|
10510 day*ug/mL
Standard Deviation 3036
|
—
|
—
|
—
|
|
PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1
AUClast
|
10310 day*ug/mL
Standard Deviation 2869
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=25 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=11 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=11 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1 and 2
AUCinf
|
10880 day*ug/mL
Standard Deviation 2983
|
1025 day*ug/mL
Standard Deviation 276.0
|
198.0 day*ug/mL
Standard Deviation 195.5
|
—
|
|
PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1 and 2
AUClast
|
10630 day*ug/mL
Standard Deviation 2818
|
993.0 day*ug/mL
Standard Deviation 279.5
|
187.7 day*ug/mL
Standard Deviation 190.7
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=20 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1
|
0.1594 Liters/day
Standard Deviation 0.04998
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=25 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=11 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=11 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 and 2
|
0.1571 Liters/day
Standard Deviation 0.04734
|
0.1718 Liters/day
Standard Deviation 0.04942
|
0.1182 Liters/day
Standard Deviation 0.05474
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=20 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1
|
6.121 Liters
Standard Deviation 0.999
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=25 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=11 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=11 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 and 2
|
6.055 Liters
Standard Deviation 0.943
|
6.481 Liters
Standard Deviation 1.701
|
5.827 Liters
Standard Deviation 2.887
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=20 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1
|
27.95 day
Standard Deviation 5.624
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 28Population: Pharmacokinetic Analysis set: All patients with quantifiable PK measurements and no major protocol deviations with impact on PK data. Due to several discontinuations, the full set of PK parameters could not be obtained in all treated patients. Patients who received only one infusion and/or had a too short PK sampling period were excluded
Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=25 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=11 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=11 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 and 2
|
28.09 day
Standard Deviation 5.994
|
27.32 day
Standard Deviation 7.234
|
34.31 day
Standard Deviation 6.656
|
—
|
SECONDARY outcome
Timeframe: Baseline, day 8,15,29, week 6,8,10,12,16,20,24,28Population: Pharmacodynamic Analysis set: All patients with a least one evaluable post-treatment PD measurement and no major protocol deviations with impact on PD data were included. One subjects was excluded from the PD set in the AIN457 10mg/kg Part 2 due to the absence of available post-baseline PD measurements
BASMI measures the range of motion based on five clinical measurements: 1) cervical rotation, 2) tragus to wall distance, 3) lumbar side flexion, 4) lumbar flexion (modified Schober's) and 5) intermalleolar distance. BASMI 0 = indicates mild disease involvement, 1 = moderate disease, and 2 = severe disease involvement. The results for cervical rotation and lumbar side flexion are the means of the left and right measurements. Scoring range 0-10. The higher the BASMI score, the more severe was the subject's limitation of movement
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=28 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=12 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=12 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
Day 15 (n=28,12,12,5)
|
-0.200 Score
Standard Deviation 0.7364
|
-0.383 Score
Standard Deviation 0.5937
|
-0.350 Score
Standard Deviation 0.7775
|
0.160 Score
Standard Deviation 0.8764
|
|
Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
Week 10 (n=25,11,10,3)
|
-0.376 Score
Standard Deviation 0.8686
|
-0.200 Score
Standard Deviation 0.9077
|
-0.400 Score
Standard Deviation 0.6325
|
-0.067 Score
Standard Deviation 0.4163
|
|
Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
Week 16 (n=24,10,8,3)
|
-0.200 Score
Standard Deviation 0.8299
|
-0.400 Score
Standard Deviation 0.7424
|
-0.550 Score
Standard Deviation 0.9304
|
0.400 Score
Standard Deviation 0.8000
|
|
Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
Week 28 (n=28,11,11,5)
|
-0.036 Score
Standard Deviation 0.7345
|
-0.182 Score
Standard Deviation 0.9527
|
-0.230 Score
Standard Deviation 0.8145
|
0.400 Score
Standard Deviation 0.4690
|
|
Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
Day 8 (n=28,12,12,5)
|
-0.121 Score
Standard Deviation 0.7969
|
-0.117 Score
Standard Deviation 0.6293
|
-0.233 Score
Standard Deviation 0.9335
|
0.240 Score
Standard Deviation 0.2966
|
|
Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
Day 29 (n=28,12,11,6)
|
-0.157 Score
Standard Deviation 0.8404
|
-0.417 Score
Standard Deviation 0.7259
|
-0.382 Score
Standard Deviation 1.0713
|
0.100 Score
Standard Deviation 0.2098
|
|
Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
Week 6 (n=27,11,11,3)
|
-0.281 Score
Standard Deviation 0.8138
|
-0.436 Score
Standard Deviation 0.7256
|
-0.291 Score
Standard Deviation 0.8961
|
0.133 Score
Standard Deviation 0.6110
|
|
Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
Week 8 (n=26,11,11,3)
|
-0.238 Score
Standard Deviation 0.8100
|
-0.518 Score
Standard Deviation 1.0925
|
-0.509 Score
Standard Deviation 0.9523
|
-0.133 Score
Standard Deviation 0.6110
|
|
Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
Week 12 (n=25,12,11,3)
|
-0.384 Score
Standard Deviation 0.8887
|
-0.267 Score
Standard Deviation 0.7738
|
-0.455 Score
Standard Deviation 0.9883
|
-0.200 Score
Standard Deviation 0.6928
|
|
Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
Week 20 (n=21,9,6,3)
|
-0.143 Score
Standard Deviation 0.9168
|
-0.356 Score
Standard Deviation 0.6064
|
-0.633 Score
Standard Deviation 1.0912
|
-0.200 Score
Standard Deviation 1.5875
|
|
Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
Week 24 (n=20,8,5,3)
|
-0.250 Score
Standard Deviation 0.7564
|
0.200 Score
Standard Deviation 0.5657
|
-0.800 Score
Standard Deviation 1.1045
|
0.400 Score
Standard Deviation 0.7211
|
SECONDARY outcome
Timeframe: Baseline, day 8,15,29,week 6,8,10,12,16,20,24,28Population: Pharmacodynamic Analysis set: All patients with a least one evaluable post-treatment PD measurement and no major protocol deviations with impact on PD data were included. One subjects was excluded from the PD set in the AIN457 10mg/kg Part 2 due to the absence of available post-baseline PD measurements
The BASDAI consists of a 1 through 10 scale (1 being no problem and 10 being the worst problem), which was used to answer 6 questions pertaining to the 5 major symptoms of AS: Fatigue, Spinal pain, Joint pain / swelling, areas of localized tenderness (called enthesitis, or inflammation of insertion sites of tendons and ligaments), morning stiffness duration, and morning stiffness severity. The physician will globally assess the subject's current disease state using a visual analog scale (VAS) scale with 0 being very good and 100 being very bad.
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=28 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=12 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=12 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
Day 15 (n=28,12,11,5)
|
-1.7094 Score
Interval -2.485 to -0.934
|
-2.1256 Score
Interval -3.317 to -0.934
|
-1.1263 Score
Interval -2.376 to 0.124
|
-0.6417 Score
Interval -2.199 to 0.915
|
|
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
Week 20 (n=21,9,6,3)
|
-1.2072 Score
Interval -2.011 to -0.403
|
-1.4070 Score
Interval -2.632 to -0.183
|
-1.1596 Score
Interval -2.521 to 0.202
|
-1.5864 Score
Interval -3.385 to 0.212
|
|
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
Week 24 (n=20,8,5,3)
|
-1.1318 Score
Interval -2.001 to -0.262
|
-1.0035 Score
Interval -2.343 to 0.336
|
-0.8020 Score
Interval -2.305 to 0.701
|
-1.2048 Score
Interval -3.201 to 0.792
|
|
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
Week 28 (n=28,11,11,5)
|
-0.7373 Score
Interval -1.487 to 0.012
|
-0.8980 Score
Interval -2.057 to 0.261
|
-1.2227 Score
Interval -2.432 to -0.013
|
-0.9722 Score
Interval -2.526 to 0.582
|
|
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
Day 8 (n=28,12,11,6)
|
-1.7011 Score
Interval -2.533 to -0.87
|
-1.2793 Score
Interval -2.559 to 0.001
|
-1.2920 Score
Interval -2.635 to 0.051
|
-1.0837 Score
Interval -2.737 to 0.57
|
|
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
Day 29 (n=28,12,11,6)
|
-2.2530 Score
Interval -3.096 to -1.41
|
-2.4237 Score
Interval -3.722 to -1.126
|
-1.3886 Score
Interval -2.75 to -0.028
|
-0.7839 Score
Interval -2.464 to 0.896
|
|
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
Week 6 (n=26,11,11,3)
|
-1.8713 Score
Interval -2.691 to -1.051
|
-2.0151 Score
Interval -3.275 to -0.755
|
-1.2002 Score
Interval -2.514 to 0.113
|
-1.0577 Score
Interval -2.893 to 0.777
|
|
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
Week 8 (n=26,11,11,3)
|
-1.3863 Score
Interval -2.189 to -0.584
|
-1.6994 Score
Interval -2.933 to -0.466
|
-1.2020 Score
Interval -2.485 to 0.081
|
-1.4619 Score
Interval -3.401 to 0.477
|
|
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
Week 10 (n=24,11,9,3)
|
-1.6246 Score
Interval -2.389 to -0.86
|
-1.7402 Score
Interval -2.909 to -0.571
|
-1.0800 Score
Interval -2.313 to 0.153
|
-0.8527 Score
Interval -2.558 to 0.853
|
|
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
Week 12 (n=24,12,11,3)
|
-1.4744 Score
Interval -2.336 to -0.613
|
-1.3755 Score
Interval -2.688 to -0.063
|
-1.6834 Score
Interval -3.059 to -0.307
|
-1.3529 Score
Interval -3.354 to 0.648
|
|
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
Week 16 (n=24,10,8,3)
|
-1.3990 Score
Interval -2.237 to -0.562
|
-2.3081 Score
Interval -3.589 to -1.027
|
-1.7628 Score
Interval -3.143 to -0.383
|
-1.4083 Score
Interval -3.415 to 0.598
|
SECONDARY outcome
Timeframe: Baseline, day 8,15,29,week, 6, 8,10,12,16,20,24,28Population: Pharmacodynamic Analysis set: All patients with a least one evaluable post-treatment PD measurement and no major protocol deviations with impact on PD data were included. One subjects was excluded from the PD set in the AIN457 10mg/kg Part 1 due to protocol deviation
MASES is measured by scoring of entheses of 0 (no tenderness) to 3 (severe tenderness) at 13 sites on the body. The score was derived as the sum of the 13 scores divided by 3 and the total range is 0 (no tenderness) to 13 (severe tenderness).
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=23 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
Day 15 (n=23,5)
|
-1.3 Score
Standard Deviation 2.53
|
2.4 Score
Standard Deviation 2.51
|
—
|
—
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
Day 29 (n=23,6)
|
-1.0 Score
Standard Deviation 2.80
|
-0.3 Score
Standard Deviation 1.97
|
—
|
—
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
Week 6 (n=22,3)
|
-1.5 Score
Standard Deviation 3.10
|
-0.3 Score
Standard Deviation 0.58
|
—
|
—
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
Week 8 (n=21,3)
|
-1.0 Score
Standard Deviation 2.77
|
0.0 Score
Standard Deviation 0.0
|
—
|
—
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
Week 12 (n=20,3)
|
-1.2 Score
Standard Deviation 3.09
|
-0.3 Score
Standard Deviation 0.58
|
—
|
—
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
Week 16 (n=30,3)
|
-0.9 Score
Standard Deviation 3.69
|
-0.3 Score
Standard Deviation 0.58
|
—
|
—
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
Week 20 (n=18,3)
|
0.2 Score
Standard Deviation 3.55
|
0.3 Score
Standard Deviation 1.53
|
—
|
—
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
Week 24 (n=17,3)
|
-1.3 Score
Standard Deviation 2.11
|
-0.3 Score
Standard Deviation 0.58
|
—
|
—
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
Week 28 (n=23,5)
|
-0.4 Score
Standard Deviation 3.86
|
1.2 Score
Standard Deviation 1.30
|
—
|
—
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
Week 10 (n=20,3)
|
-1.3 Score
Standard Deviation 3.24
|
-0.3 Score
Standard Deviation 0.58
|
—
|
—
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
Day 8 (n=23,6)
|
-1.3 Score
Standard Deviation 2.46
|
0.7 Score
Standard Deviation 1.37
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 8,15,29,week, 6, 10,12,16,20,24,28Population: Pharmacodynamic Analysis set: All patients with a least one evaluable post-treatment PD measurement and no major protocol deviations with impact on PD data were included. One subjects was excluded from the PD set in the AIN457 10mg/kg Part 2 due to the absence of available post-baseline PD measurements
MASES is measured by scoring of entheses of 0 (no tenderness) to 3 (severe tenderness) at 13 sites on the body. The score was derived as the sum of the 13 scores divided by 3 and the total range is 0 (no tenderness) to 13 (severe tenderness).
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=28 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=12 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=12 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1 and 2
Day 8 (n=28,12,12,6)
|
-1.321 Score
Standard Deviation 2.7763
|
-1.917 Score
Standard Deviation 2.2344
|
-0.583 Score
Standard Deviation 1.0836
|
0.667 Score
Standard Deviation 1.3663
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1 and 2
Day 15 (n=28,12,12,5)
|
-1.393 Score
Standard Deviation 2.7667
|
-1.167 Score
Standard Deviation 1.9924
|
-1.167 Score
Standard Deviation 1.9462
|
2.400 Score
Standard Deviation 2.5100
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1 and 2
Day 29 (n=28,12,11,6)
|
-1.143 Score
Standard Deviation 2.9779
|
-2.083 Score
Standard Deviation 2.2344
|
-0.545 Score
Standard Deviation 0.6876
|
-0.333 Score
Standard Deviation 1.9664
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1 and 2
Week 6 (n=27,11,11,3)
|
-1.556 Score
Standard Deviation 3.2026
|
-0.339 Score
Standard Deviation 3.1318
|
-0.364 Score
Standard Deviation 1.0269
|
-0.333 Score
Standard Deviation 0.5774
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1 and 2
Week 8 (n=26,11,11,3)
|
-1.154 Score
Standard Deviation 2.9758
|
-1.273 Score
Standard Deviation 1.6787
|
0.455 Score
Standard Deviation 2.2523
|
0.0 Score
Standard Deviation 0.0
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1 and 2
Week 10 (n=25,11,10,3)
|
-1.360 Score
Standard Deviation 3.3277
|
-1.091 Score
Standard Deviation 3.1450
|
-0.800 Score
Standard Deviation 0.9189
|
-0.333 Score
Standard Deviation 0.5774
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1 and 2
Week 24 (n=20,8,5,3)
|
-1.400 Score
Standard Deviation 2.2572
|
-1.000 Score
Standard Deviation 3.7417
|
0.600 Score
Standard Deviation 1.9494
|
-0.333 Score
Standard Deviation 0.5774
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1 and 2
Week 12 (n=25,12,11,3)
|
-1.280 Score
Standard Deviation 3.2342
|
-1.167 Score
Standard Deviation 4.1304
|
-0.636 Score
Standard Deviation 1.8040
|
-0.333 Score
Standard Deviation 0.5774
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1 and 2
Week 16 (n=24,10,8,3)
|
-1.042 Score
Standard Deviation 3.7819
|
-0.600 Score
Standard Deviation 3.4705
|
0.500 Score
Standard Deviation 1.6903
|
-0.333 Score
Standard Deviation 0.5774
|
|
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1 and 2
Week 20 (n=21,9,6,3)
|
-0.238 Score
Standard Deviation 3.8458
|
-0.333 Score
Standard Deviation 3.7749
|
-0.667 Score
Standard Deviation 1.3663
|
0.333 Score
Standard Deviation 1.5275
|
SECONDARY outcome
Timeframe: SF-36:Baseline, week 12, week 28; ASQoL: Baseline, Day 29, week 12, week 28Population: Pharmacodynamic Analysis set: All patients with a least one evaluable post-treatment PD measurement and no major protocol deviations with impact on PD data were included. One subjects was excluded from the PD set in the AIN457 10mg/kg Part 2 due to the absence of available post-baseline PD measurements
The Short Form (36) Health Survey (SF-36) measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score. Scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health. ASQoL determined subject's quality of life and is comprised of 18 questions (yes or no) to be completed by the subject. Each statement on the ASQoL is given a score of "1" or "0." All item scores were summed to give a total score or index. Total scores ranged from 0 (good quality of life) to 18 (poor quality of life) related to ability to cope, relationships, mood, sleep, motivation, activities of everyday living, independence, and social life. Decrease in ASQoL score represents improvement.
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=23 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1.
Week 12 SF36 Mental component (n=20,3)
|
43.45 Score
Standard Deviation 10.56
|
56.57 Score
Standard Deviation 5.39
|
—
|
—
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1.
Baseline SF36 Mental component (n= 22,6)
|
38.71 Score
Standard Deviation 10.78
|
39.57 Score
Standard Deviation 14.63
|
—
|
—
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1.
Baseline SF36 physical component (n=22,6)
|
31.42 Score
Standard Deviation 5.2
|
30.11 Score
Standard Deviation 6.71
|
—
|
—
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1.
Week 12 SF36 Physical component (n=20,3)
|
32.84 Score
Standard Deviation 6.39
|
28.95 Score
Standard Deviation 1.8
|
—
|
—
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1.
Week 28 SF36 Mental component (n=21,4)
|
41.65 Score
Standard Deviation 9.86
|
40.51 Score
Standard Deviation 15.22
|
—
|
—
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1.
Week 28 SF36 Physical component (n=21,4)
|
32.2 Score
Standard Deviation 5.68
|
33.96 Score
Standard Deviation 8.73
|
—
|
—
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1.
Change from Baseline to Day 29 ASQoL (n=21,6)
|
-2.9 Score
Standard Deviation 4.04
|
-0.7 Score
Standard Deviation 2.58
|
—
|
—
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1.
Change from Baseline to Week 12 ASQoL (n=18,3)
|
-2.3 Score
Standard Deviation 3.05
|
0.0 Score
Standard Deviation 1.00
|
—
|
—
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1.
Change from Baseline to Week 28 ASQoL (n=20,4)
|
-1.2 Score
Standard Deviation 3.71
|
-1.3 Score
Standard Deviation 2.06
|
—
|
—
|
SECONDARY outcome
Timeframe: SF-36: Baseline, week 12, week 28; ASQoL: Baseline, day 29, week 12, week 8Population: Pharmacodynamic Analysis set: All patients with a least one evaluable post-treatment PD measurement and no major protocol deviations with impact on PD data were included. One subjects was excluded from the PD set in the AIN457 10mg/kg Part 2 due to the absence of available post-baseline PD measurements
The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score. ASQoL determined subject's quality of life and is comprised of 18 questions (yes or no) to be completed by the subject. Each statement on the ASQoL is given a score of "1" or "0." All item scores were summed to give a total score or index. Total scores ranged from 0 (good quality of life) to 18 (poor quality of life) related to ability to cope, relationships, mood, sleep, motivation, activities of everyday living, independence, and social life. Decrease in ASQoL score represents improvement.
Outcome measures
| Measure |
Part 1 - AIN457A 10 mg/kg
n=28 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=12 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
Part 1 and 2 - AIN457 0.1 mg/kg
n=12 Participants
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Part 1 and 2 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1 and 2.
Baseline SF36 Physical component (n=27,12,12,6)
|
30.95 Score
Standard Deviation 6.34
|
26.17 Score
Standard Deviation 7.63
|
33.53 Score
Standard Deviation 7.47
|
30.11 Score
Standard Deviation 6.71
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1 and 2.
Baseline SF36 Mental component (n=27,12,12,6)
|
38.97 Score
Standard Deviation 10.91
|
39.46 Score
Standard Deviation 11.95
|
51.9 Score
Standard Deviation 8.7
|
39.57 Score
Standard Deviation 14.63
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1 and 2.
Week 12 SF36 Mental component (n=25,11,10,3)
|
44.37 Score
Standard Deviation 11.05
|
38.45 Score
Standard Deviation 10.13
|
49.7 Score
Standard Deviation 11.74
|
56.57 Score
Standard Deviation 5.39
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1 and 2.
Week 12 SF36 Physical component (n=25,11,10,3)
|
32.71 Score
Standard Deviation 6.24
|
31.3 Score
Standard Deviation 7.67
|
35.81 Score
Standard Deviation 5.29
|
28.05 Score
Standard Deviation 1.8
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1 and 2.
Week 28 SF36 Mental component (n=26,11,10,4)
|
40.94 Score
Standard Deviation 10.56
|
36.6 Score
Standard Deviation 10.3
|
46.96 Score
Standard Deviation 9.67
|
40.51 Score
Standard Deviation 15.22
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1 and 2.
Week 28 SF36 Physical component (n=26,11,10,4)
|
31.85 Score
Standard Deviation 5.3
|
29.95 Score
Standard Deviation 6.92
|
35.54 Score
Standard Deviation 5.9
|
33.96 Score
Standard Deviation 8.73
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1 and 2.
Change from Baseline to Day 29 ASQoL(n=26,11,10,6)
|
-3.2 Score
Standard Deviation 3.78
|
-3.1 Score
Standard Deviation 2.63
|
-0.7 Score
Standard Deviation 2.26
|
-0.7 Score
Standard Deviation 2.58
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1 and 2.
Change from Baseline to Week 12 ASQoL(n=23,11,9,3)
|
-2.7 Score
Standard Deviation 2.91
|
-2.7 Score
Standard Deviation 4.71
|
-1.3 Score
Standard Deviation 3.16
|
0.0 Score
Standard Deviation 1.00
|
|
Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1 and 2.
Change from Baseline to Week 28 ASQoL(n=25,11,9,4)
|
-1.4 Score
Standard Deviation 3.37
|
-1.3 Score
Standard Deviation 3.66
|
-0.9 Score
Standard Deviation 2.15
|
-1.3 Score
Standard Deviation 2.06
|
Adverse Events
AIN457 2x10mg/kg
AIN457 2x1.0mg/kg
AIN457 2x0.1mg/kg
Placebo
Serious adverse events
| Measure |
AIN457 2x10mg/kg
n=30 participants at risk
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
AIN457 2x1.0mg/kg
n=12 participants at risk
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
AIN457 2x0.1mg/kg
n=12 participants at risk
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Placebo
n=6 participants at risk
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Immune system disorders
Anaphylactic reaction
|
3.3%
1/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Infections and infestations
Cytomegalovirus infection
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Infections and infestations
Subcutaneous abscess
|
3.3%
1/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Investigations
Blood pressure increased
|
0.00%
0/30
|
0.00%
0/12
|
0.00%
0/12
|
16.7%
1/6
|
Other adverse events
| Measure |
AIN457 2x10mg/kg
n=30 participants at risk
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
AIN457 2x1.0mg/kg
n=12 participants at risk
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
AIN457 2x0.1mg/kg
n=12 participants at risk
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22
|
Placebo
n=6 participants at risk
Placebo to AIN457A was administered intravenously as a single dose
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Cardiac disorders
Cardiovascular insufficiency
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Cardiac disorders
Palpitations
|
0.00%
0/30
|
0.00%
0/12
|
0.00%
0/12
|
16.7%
1/6
|
|
Ear and labyrinth disorders
Vertigo
|
6.7%
2/30
|
8.3%
1/12
|
0.00%
0/12
|
16.7%
1/6
|
|
Eye disorders
Eye swelling
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Eye disorders
Vision blurred
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Eye disorders
Vitreous floaters
|
0.00%
0/30
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain
|
3.3%
1/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.7%
2/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
3.3%
1/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhoea
|
23.3%
7/30
|
0.00%
0/12
|
16.7%
2/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Frequent bowel movements
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/30
|
8.3%
1/12
|
8.3%
1/12
|
16.7%
1/6
|
|
Gastrointestinal disorders
Mouth ulceration
|
6.7%
2/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Nausea
|
20.0%
6/30
|
8.3%
1/12
|
8.3%
1/12
|
16.7%
1/6
|
|
Gastrointestinal disorders
Oral mucosal eruption
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Pancreatic enlargement
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Stomatitis
|
3.3%
1/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
1/30
|
8.3%
1/12
|
0.00%
0/12
|
16.7%
1/6
|
|
General disorders
Chills
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
16.7%
1/6
|
|
General disorders
Fatigue
|
10.0%
3/30
|
0.00%
0/12
|
25.0%
3/12
|
16.7%
1/6
|
|
General disorders
Influenza like illness
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
General disorders
Malaise
|
6.7%
2/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
General disorders
Pain
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
General disorders
Pyrexia
|
16.7%
5/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
General disorders
Temperature intolerance
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Infections and infestations
Bronchitis
|
6.7%
2/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Infections and infestations
Fungal skin infection
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Infections and infestations
Gastroenteritis
|
6.7%
2/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Infections and infestations
Influenza
|
10.0%
3/30
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Infections and infestations
Nasopharyngitis
|
26.7%
8/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Infections and infestations
Oral candidiasis
|
6.7%
2/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Infections and infestations
Oral herpes
|
6.7%
2/30
|
0.00%
0/12
|
0.00%
0/12
|
16.7%
1/6
|
|
Infections and infestations
Otitis externa
|
6.7%
2/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Infections and infestations
Otitis media
|
3.3%
1/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Infections and infestations
Rhinitis
|
6.7%
2/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Infections and infestations
Sinusitis
|
3.3%
1/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Infections and infestations
Upper respiratory tract infection
|
6.7%
2/30
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Epicondylitis
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Investigations
Aortic bruit
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Ankylosing spondylitis
|
3.3%
1/30
|
0.00%
0/12
|
8.3%
1/12
|
33.3%
2/6
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.3%
4/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
3/30
|
0.00%
0/12
|
8.3%
1/12
|
16.7%
1/6
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Bone swelling
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/30
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.7%
2/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.3%
1/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Tendon calcification
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Nervous system disorders
Burning sensation
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Nervous system disorders
Dizziness
|
10.0%
3/30
|
8.3%
1/12
|
0.00%
0/12
|
16.7%
1/6
|
|
Nervous system disorders
Dysaesthesia
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Nervous system disorders
Dysgeusia
|
6.7%
2/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Nervous system disorders
Headache
|
23.3%
7/30
|
8.3%
1/12
|
25.0%
3/12
|
0.00%
0/6
|
|
Nervous system disorders
Paraesthesia
|
10.0%
3/30
|
8.3%
1/12
|
0.00%
0/12
|
16.7%
1/6
|
|
Nervous system disorders
Sinus headache
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Nervous system disorders
Tremor
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Psychiatric disorders
Insomnia
|
3.3%
1/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/30
|
0.00%
0/12
|
0.00%
0/12
|
16.7%
1/6
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.7%
2/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.3%
1/30
|
8.3%
1/12
|
16.7%
2/12
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
10.0%
3/30
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
3.3%
1/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Dyshidrosis
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.7%
2/30
|
0.00%
0/12
|
8.3%
1/12
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/30
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Vascular disorders
Circulatory collapse
|
6.7%
2/30
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/6
|
|
Vascular disorders
Flushing
|
0.00%
0/30
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/6
|
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