Trial Outcomes & Findings for Efficacy of AIN457 in Adults (18-65 Years) With Psoriatic Arthritis (NCT NCT00809614)
NCT ID: NCT00809614
Last Updated: 2015-11-13
Results Overview
A participant was considered to be a responder according to the ACR20, 50 or 70 criteria if the participant had at least 20% 50% or 70% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)
COMPLETED
PHASE2
42 participants
week 6
2015-11-13
Participant Flow
A total of 42 patients were planned and recruited. The patients were randomized to either AIN457 2x10 mg/kg or placebo in a ratio of 2:1. The total sample size of 42 included an additional 3 subjects to allow for drop-outs and/or incomplete data.
Participant milestones
| Measure |
AIN457 (2x 10mg/kg)
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Overall Study
STARTED
|
28
|
14
|
|
Overall Study
Pharmacokinetic Safety Set
|
27
|
14
|
|
Overall Study
Pharmacodynamic (PD) Set
|
24
|
13
|
|
Overall Study
COMPLETED
|
25
|
10
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
| Measure |
AIN457 (2x 10mg/kg)
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
2
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
Efficacy of AIN457 in Adults (18-65 Years) With Psoriatic Arthritis
Baseline characteristics by cohort
| Measure |
AIN457 (2x 10mg/kg)
n=28 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=14 Participants
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
Total
n=42 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46.7 Years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
47.6 Years
STANDARD_DEVIATION 8.1 • n=7 Participants
|
47.0 Years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: week 6Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations.
A participant was considered to be a responder according to the ACR20, 50 or 70 criteria if the participant had at least 20% 50% or 70% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=13 Participants
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Percentage of ACR Responders Per Treatment at Week 6
ACR20 responders
|
39 Percentage of ACR responders
|
23 Percentage of ACR responders
|
|
Percentage of ACR Responders Per Treatment at Week 6
ACR50 responders
|
17 Percentage of ACR responders
|
8 Percentage of ACR responders
|
|
Percentage of ACR Responders Per Treatment at Week 6
ACR70 responders
|
9 Percentage of ACR responders
|
0 Percentage of ACR responders
|
PRIMARY outcome
Timeframe: week 6Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations.
Psoriatic Arthritis Response Criteria (PsARC) includes measures of tender and swollen joint counts, patient's assessment of pain, physician's and patient's global assessment of disease activity A subject is defined as a PsARC responder if, and only if, they have an improvement in two of the following four factors (with at least one factor being a joint count) and no worsening in the remaining factors: 1) Patient global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 2) Physician global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 3) Tender 78-joint count (improvement defined as decrease of at least 30%) 4) Swollen 76-joint count (improvement defined as decrease of at least 30%)
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=13 Participants
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Percentage of PsARC Responders Per Treatment at Week 6
|
43 Percentage of PsARC responders
|
38 Percentage of PsARC responders
|
SECONDARY outcome
Timeframe: Day 8 and 15, Weeks 6, 8, 12, 16 and 24Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocoldeviations.
A participant was considered to be a responder according to the ACR20, 50 or 70 criteria if the participant had at least 20% 50% or 70% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=13 Participants
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 24 ACR50 responders
|
17 Percentage of particpants
|
9 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Day 15 ACR70 responders
|
0 Percentage of particpants
|
0 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Day 8 ACR20 responders
|
17 Percentage of particpants
|
8 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Day 8 ACR50 responders
|
0 Percentage of particpants
|
0 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Day 8 ACR70 responders
|
0 Percentage of particpants
|
0 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Day 15 ACR20 responders
|
25 Percentage of particpants
|
17 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Day 15 ACR50 responders
|
13 Percentage of particpants
|
0 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 6 ACR20 responders
|
39 Percentage of particpants
|
23 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 6 ACR50 responders
|
17 Percentage of particpants
|
8 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 6 ACR70 responders
|
9 Percentage of particpants
|
0 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 8 ACR20 responders
|
42 Percentage of particpants
|
23 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 8 ACR50 responders
|
29 Percentage of particpants
|
8 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 8 ACR70 responders
|
17 Percentage of particpants
|
0 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 12 ACR20 responders
|
39 Percentage of particpants
|
15 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 12 ACR50 responders
|
22 Percentage of particpants
|
8 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 12 ACR70 responders
|
9 Percentage of particpants
|
8 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 16 ACR20 responders
|
41 Percentage of particpants
|
27 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 16 ACR50 responders
|
27 Percentage of particpants
|
18 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 16 ACR70 responders
|
18 Percentage of particpants
|
9 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 24 ACR20 responders
|
43 Percentage of particpants
|
18 Percentage of particpants
|
|
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria
Week 24 ACR70 responders
|
13 Percentage of particpants
|
9 Percentage of particpants
|
SECONDARY outcome
Timeframe: Day 8 and 15, Weeks 6, 8, 12, 16 and 24Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations.
responder" defined as 20% or more improvement in at least 4 of 6 criteria: 1) swollen joint count, 2) tender joint count, 3) morning stiffness duration (low back), 4) current low back pain, 5) current peripheral joint pain, 6) patient global assessment A subject is defined as a PsARC responder if, and only if, they have an improvement in two of the following four factors (with at least one factor being a joint count) and no worsening in the remaining factors: 1) Patient global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 2) Physician global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 3) Tender 78-joint count (improvement defined as decrease of at least 30%) 4) Swollen 76-joint count (improvement defined as decrease of at least 30%)
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=13 Participants
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Percentage of Participants Who Achieved PsARC Response
Day 8
|
27 Percentage of participants
|
23 Percentage of participants
|
|
Percentage of Participants Who Achieved PsARC Response
Day 15
|
33 Percentage of participants
|
15 Percentage of participants
|
|
Percentage of Participants Who Achieved PsARC Response
Week 6
|
43 Percentage of participants
|
38 Percentage of participants
|
|
Percentage of Participants Who Achieved PsARC Response
Week 8
|
52 Percentage of participants
|
38 Percentage of participants
|
|
Percentage of Participants Who Achieved PsARC Response
Week 12
|
52 Percentage of participants
|
15 Percentage of participants
|
|
Percentage of Participants Who Achieved PsARC Response
Week 16
|
55 Percentage of participants
|
36 Percentage of participants
|
|
Percentage of Participants Who Achieved PsARC Response
Week 24
|
50 Percentage of participants
|
36 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Day 8, 15 and weeks 6, 8, 12, 16 and 24Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations
The MASES included assessments of 13 sites. Enthesitis sites included in the MASES index are: 1st costochondral, 7th costochondral, posterior superior iliac spine, anterior superior iliac spine, iliac crest (all above was assessed bilaterally), 5th lumbar spinous process, proximal Achilles (bilateral). The MASES score is defined as the total number of painful MASES entheses. 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 |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=13 Participants
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment
Baseline (n=24,13)
|
3.0 Units on a scale
Standard Deviation 4.12
|
3.4 Units on a scale
Standard Deviation 2.33
|
|
Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment
Day 8 (n=23,13)
|
2.6 Units on a scale
Standard Deviation 4.30
|
2.7 Units on a scale
Standard Deviation 2.59
|
|
Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment
Day 15 (24,13)
|
2.9 Units on a scale
Standard Deviation 4.81
|
2.8 Units on a scale
Standard Deviation 3.42
|
|
Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment
Week 6 (n=23,11)
|
2.6 Units on a scale
Standard Deviation 4.68
|
2.8 Units on a scale
Standard Deviation 3.34
|
|
Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment
Week 8 (n=22,11)
|
2.7 Units on a scale
Standard Deviation 4.14
|
2.6 Units on a scale
Standard Deviation 3.32
|
|
Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment
Week 12 (n=20,11)
|
2.4 Units on a scale
Standard Deviation 4.06
|
2.5 Units on a scale
Standard Deviation 2.62
|
|
Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment
Week 16 (n=19,9)
|
2.6 Units on a scale
Standard Deviation 4.78
|
2.0 Units on a scale
Standard Deviation 2.40
|
|
Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment
Week 24 (n=23,11)
|
1.6 Units on a scale
Standard Deviation 3.88
|
2.7 Units on a scale
Standard Deviation 3.32
|
SECONDARY outcome
Timeframe: Baseline, Day 8, 15 and weeks 6, 8, 12, 16, 20 and 24Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations
The PASI assessed the extent of psoriasis on four body surface areas (head, trunk and upper and lower limbs) and the degree of plaque erythema, scaling and thickness. The PASI score accounted for the extent of body surface area affected by the erythema, scaling and thickness, and the severity of these measures. The score ranged from 0 (no disease) to 72 (maximal disease).
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=13 Participants
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Psoriatic Area and Severity Index (PASI) Score in Patients Over Time Per Treatment
Week 24 (n=23,11)
|
1.2 Unit on a Scale
Standard Deviation 1.67
|
3.6 Unit on a Scale
Standard Deviation 5.39
|
|
Psoriatic Area and Severity Index (PASI) Score in Patients Over Time Per Treatment
Baseline (n=24,13)
|
3.5 Unit on a Scale
Standard Deviation 4.20
|
2.4 Unit on a Scale
Standard Deviation 2.13
|
|
Psoriatic Area and Severity Index (PASI) Score in Patients Over Time Per Treatment
Week 6 (n=23,11)
|
1.0 Unit on a Scale
Standard Deviation 1.5
|
3.10 Unit on a Scale
Standard Deviation 4.94
|
|
Psoriatic Area and Severity Index (PASI) Score in Patients Over Time Per Treatment
Week 12 (n=20,11)
|
0.71 Unit on a Scale
Standard Deviation 1.12
|
3.3 Unit on a Scale
Standard Deviation 5.90
|
|
Psoriatic Area and Severity Index (PASI) Score in Patients Over Time Per Treatment
Day 8 (n=23,13)
|
2.2 Unit on a Scale
Standard Deviation 2.77
|
2.3 Unit on a Scale
Standard Deviation 2.34
|
|
Psoriatic Area and Severity Index (PASI) Score in Patients Over Time Per Treatment
Day 15 (n=24,13)
|
2.2 Unit on a Scale
Standard Deviation 2.92
|
2.2 Unit on a Scale
Standard Deviation 2.79
|
|
Psoriatic Area and Severity Index (PASI) Score in Patients Over Time Per Treatment
Week 8 (n=22,11)
|
0.91 Unit on a Scale
Standard Deviation 1.43
|
3.5 Unit on a Scale
Standard Deviation 6.57
|
|
Psoriatic Area and Severity Index (PASI) Score in Patients Over Time Per Treatment
Week 16 (n=19,9)
|
0.91 Unit on a Scale
Standard Deviation 1.25
|
4.2 Unit on a Scale
Standard Deviation 8.13
|
|
Psoriatic Area and Severity Index (PASI) Score in Patients Over Time Per Treatment
Week 20 (n=19,8)
|
0.85 Unit on a Scale
Standard Deviation 1.36
|
3.84 Unit on a Scale
Standard Deviation 6.66
|
SECONDARY outcome
Timeframe: Baseline, Day 8, 15 and weeks 6, 8, 12, 16 and 24Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations
SPARCC evaluated 18 enthesis sites: medial and lateral epicondyle humerus, supraspinatus insertion, proximal Achilles, greater trochanter, medial and lateral condyl femur, insertion of plantar fascia, quadriceps insertion of patella, inferior pole of patella, and tibial tubercle. SPARCC enthesis index is defined as the total number of painful entheses assessed at the SPARCC sites. Total SI joint scores could range from 0 to 78, with a higher score indicating more signs of disease.
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=13 Participants
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
SpA Research Consortium of Canada (SPARCC) Score Score in Patients Over Time Per Treatment
Baseline (n=24,13)
|
4.42 Unit on a scale
Standard Deviation 5.055
|
6.08 Unit on a scale
Standard Deviation 4.406
|
|
SpA Research Consortium of Canada (SPARCC) Score Score in Patients Over Time Per Treatment
Week 6 (n=23,11)
|
3.65 Unit on a scale
Standard Deviation 5.515
|
4.27 Unit on a scale
Standard Deviation 4.880
|
|
SpA Research Consortium of Canada (SPARCC) Score Score in Patients Over Time Per Treatment
Week 12 (n=20,11)
|
4.10 Unit on a scale
Standard Deviation 5.428
|
5.27 Unit on a scale
Standard Deviation 4.452
|
|
SpA Research Consortium of Canada (SPARCC) Score Score in Patients Over Time Per Treatment
Week 24 (n=23,11)
|
3.22 Unit on a scale
Standard Deviation 5.161
|
4.36 Unit on a scale
Standard Deviation 4.884
|
|
SpA Research Consortium of Canada (SPARCC) Score Score in Patients Over Time Per Treatment
Day 8 (23,13)
|
3.78 Unit on a scale
Standard Deviation 5.054
|
4.08 Unit on a scale
Standard Deviation 3.840
|
|
SpA Research Consortium of Canada (SPARCC) Score Score in Patients Over Time Per Treatment
Day 15 (n=24,13)
|
4.50 Unit on a scale
Standard Deviation 6.400
|
4.15 Unit on a scale
Standard Deviation 4.356
|
|
SpA Research Consortium of Canada (SPARCC) Score Score in Patients Over Time Per Treatment
Week 8 (n=22,11)
|
4.45 Unit on a scale
Standard Deviation 4.993
|
4.00 Unit on a scale
Standard Deviation 4.266
|
|
SpA Research Consortium of Canada (SPARCC) Score Score in Patients Over Time Per Treatment
Week 16 (n=19,9)
|
3.86 Unit on a scale
Standard Deviation 5.844
|
3.67 Unit on a scale
Standard Deviation 3.354
|
SECONDARY outcome
Timeframe: Baseline, Day 8, 15 and weeks 6, 8, 12, 16 and 24Population: Only participants from the pharmacodynamic (PD) analysis set, who had available scores at each given time point, were analyzed for that time point. The PD analysis set included all patients with evaluable PD data with no protocol deviations that impacted PD data analysis.
The LDI basic measured the ratio of the circumference of the affected digit to the circumference of the digit on the opposite hand or foot, using a minimum difference of 10% to define a dactylitic digit. The ratio of circumference was multiplied by a tenderness score, using a modification of LDI which was a binary score (1 for tender, 0 for non-tender). If both sides were considered involved, the number was compared to data provided in a table. This modification was referred to as LDI basic and was applied in this study. The LDI required a tool to measure digital circumference and this tool was provided to the centers.
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=6 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=7 Participants
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment
Baseline (n=6,5)
|
2.74 total score
Standard Deviation 2.32
|
1.56 total score
Standard Deviation 2.35
|
|
Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment
Week 6 (n=4,5)
|
2.92 total score
Standard Deviation 2.37
|
2.14 total score
Standard Deviation 2.56
|
|
Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment
Week 12 (n=3,6)
|
2.52 total score
Standard Deviation 1.57
|
0.73 total score
Standard Deviation 0.58
|
|
Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment
Week 24 (n=2,6)
|
3.08 total score
Standard Deviation 1.54
|
1.88 total score
Standard Deviation 2.19
|
|
Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment
Day 8 (n=5,5)
|
2.65 total score
Standard Deviation 1.60
|
1.32 total score
Standard Deviation 0.94
|
|
Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment
Day 15 (n=4,5)
|
2.67 total score
Standard Deviation 2.61
|
1.72 total score
Standard Deviation 2.25
|
|
Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment
Week 8 (n=3,5)
|
2.96 total score
Standard Deviation 1.03
|
1.54 total score
Standard Deviation 2.35
|
|
Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment
Week 16 (n=3,4)
|
2.65 total score
Standard Deviation 1.82
|
2.08 total score
Standard Deviation 2.40
|
SECONDARY outcome
Timeframe: Baseline, day 8, 15 and weeks 6, 8, 12, 16 and 24Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations
The Disease Activity Score (DAS) is a combined index to measure disease activity in arthritic patients. DAS28 is determined using the following variables: 28-joint counts (tender28 and swollen28), CRP, and the participant's general health (GH) Based on the patients global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 - 100). Using the data from these variables, DAS28 is calculated using the following formula: DAS28 = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP+1) + 0.014\*GH + 0.96. The calculation results in a DAS28 score from 0 to 10 indicating the current activity of the rheumatoid arthritis of the patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6.
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=13 Participants
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment
Baseline (n=24,13)
|
4.84 Units on a scale
Standard Deviation 1.21
|
4.76 Units on a scale
Standard Deviation 1.19
|
|
Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment
Week 6 (n=28,12)
|
3.94 Units on a scale
Standard Deviation 1.47
|
4.20 Units on a scale
Standard Deviation 1.20
|
|
Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment
Week 12 (n=23,11)
|
3.62 Units on a scale
Standard Deviation 1.42
|
4.36 Units on a scale
Standard Deviation 1.41
|
|
Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment
Week 24 (n=23,11)
|
3.84 Units on a scale
Standard Deviation 1.30
|
4.28 Units on a scale
Standard Deviation 1.40
|
|
Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment
Day 8 (22,12)
|
4.19 Units on a scale
Standard Deviation 1.27
|
4.43 Units on a scale
Standard Deviation 1.27
|
|
Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment
Day 15 (24,13)
|
4.09 Units on a scale
Standard Deviation 1.26
|
4.35 Units on a scale
Standard Deviation 1.05
|
|
Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment
Week 8 (n=22,10)
|
3.66 Units on a scale
Standard Deviation 1.65
|
4.64 Units on a scale
Standard Deviation 1.22
|
|
Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment
Week 16 (n=18,9)
|
3.54 Units on a scale
Standard Deviation 1.48
|
3.83 Units on a scale
Standard Deviation 1.58
|
SECONDARY outcome
Timeframe: Day 1 till end of the study (169)Population: Only patients who recieved active drug with evaluable pharmacokinetic ( PK) parameter data and no protocol deviation that impacted PK were included in the PK data analysis set
On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=27 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Pharmacokinetic (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
|
21.0 Day
Interval 0.0833 to 23.1
|
—
|
SECONDARY outcome
Timeframe: Day 1 till end of the study (169)Population: Only patients who recieved active drug with evaluable pharmacokinetic (PK) parameter data and no protocol deviation that impacted PK were included in the PK data analysis set
On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Pharmacokinetic (PK) of AIN457: Clearance of AIN457 After Single Dose Administration
|
0.161 Liters/day
Standard Deviation 0.0535 • Interval 0.0833 to 23.1
|
—
|
SECONDARY outcome
Timeframe: Day 1 till end of the study (169)Population: Only patients who recieved active drug with evaluable pharmacokinetic (PK) parameter data and no protocol deviation that impacted PK were included in the PK data analysis set
On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Pharmacokinetic (PK) of AIN457: Terminal Elimination Half-life (T1/2)
|
29.8 day
Standard Deviation 4.74 • Interval 0.0833 to 23.1
|
—
|
SECONDARY outcome
Timeframe: Day 1 till end of the study (169)Population: Only patients who recieved active drug with evaluable pharmacokinetic (PK) parameter data and no protocol deviation that impacted PK were included in the PK data analysis set
On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=27 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Pharmacokinetic (PK) of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax)
|
424 ug/mL
Standard Deviation 113 • Interval 0.0833 to 23.1
|
—
|
SECONDARY outcome
Timeframe: Day 1 till end of the study (169)Population: Only patients who recieved active drug with evaluable pharmacokinetic (PK) parameter data and no protocol deviation that impacted PK were included in the PK data analysis set
On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
PK of AIN457: Area Under the Serum Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf)
AUClast
|
12300 day*ug/mL
Standard Deviation 2240 • Interval 0.0833 to 23.1
|
—
|
|
PK of AIN457: Area Under the Serum Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf)
AUCinf
|
12600 day*ug/mL
Standard Deviation 2320
|
—
|
SECONDARY outcome
Timeframe: Day 1 till end of the study (169)Population: Only patients who recieved active drug with evaluable pharmacokinetic (PK) parameter data and no protocol deviation that impacted PK were included in the PK data analysis set
On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
Outcome measures
| Measure |
AIN457 (2x 10mg/kg)
n=24 Participants
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Pharmacokinetic (PK) of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz)
|
6.81 Liters
Standard Deviation 2.17 • Interval 0.0833 to 23.1
|
—
|
Adverse Events
AIN457 2x10mg/kg
Placebo
Serious adverse events
| Measure |
AIN457 2x10mg/kg
n=28 participants at risk
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=14 participants at risk
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Infections and infestations
Cellulitis
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Injury, poisoning and procedural complications
Fall
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Metabolism and nutrition disorders
Obesity
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Polyarthritis
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer in situ
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Nervous system disorders
Carpal tunnel syndrome
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
Other adverse events
| Measure |
AIN457 2x10mg/kg
n=28 participants at risk
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
|
Placebo
n=14 participants at risk
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
7.1%
2/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Ear and labyrinth disorders
Hypoacusis
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Ear and labyrinth disorders
Vertigo
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
21.4%
3/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.7%
3/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Gastrointestinal disorders
Diarrhoea
|
10.7%
3/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Gastrointestinal disorders
Nausea
|
14.3%
4/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Gastrointestinal disorders
Periodontitis
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
General disorders
Chills
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
General disorders
Fatigue
|
10.7%
3/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
General disorders
Pyrexia
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Infections and infestations
Bronchitis
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Infections and infestations
Nasopharyngitis
|
25.0%
7/28
The Safety Set includes all subjects who received at least one dose of study medication
|
35.7%
5/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Infections and infestations
Oral herpes
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Injury, poisoning and procedural complications
Contusion
|
7.1%
2/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Injury, poisoning and procedural complications
Fall
|
7.1%
2/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Investigations
Neutrophil count decreased
|
7.1%
2/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Investigations
Red blood cell sedimentation rate increased
|
7.1%
2/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Investigations
White blood cell count decreased
|
7.1%
2/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Muscle tightness
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.7%
3/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Nervous system disorders
Dizziness
|
14.3%
4/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Nervous system disorders
Headache
|
21.4%
6/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Renal and urinary disorders
Haematuria
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.7%
3/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.1%
2/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.7%
3/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Vascular disorders
Haematoma
|
3.6%
1/28
The Safety Set includes all subjects who received at least one dose of study medication
|
7.1%
1/14
The Safety Set includes all subjects who received at least one dose of study medication
|
|
Vascular disorders
Hypertension
|
7.1%
2/28
The Safety Set includes all subjects who received at least one dose of study medication
|
0.00%
0/14
The Safety Set includes all subjects who received at least one dose of study medication
|
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