Trial Outcomes & Findings for Efficacy, Safety and Tolerability of Secukinumab in Patients With Rheumatoid Arthritis Taking Methotrexate (NCT NCT01359943)
NCT ID: NCT01359943
Last Updated: 2015-03-02
Results Overview
A participant was considered to be a responder according to the ACR20 criteria if the participant had at least 20% 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)/Erythrocyte Sedimentation Rate (ESR).
COMPLETED
PHASE2
221 participants
12 weeks
2015-03-02
Participant Flow
Participants were randomized to one of the following 3 treatment groups in a 2:2:1 ratio: secukinumab 10 mg/kg i.v., secukinumab 150 mg s.c. or placebo.
Participant milestones
| Measure |
Secukinumab 10 mg/kg i.v. Loading
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Secukinumab 150 mg s.c. Loading
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
|---|---|---|---|
|
Double-blind (Weeks 0 - 16)
STARTED
|
88
|
89
|
44
|
|
Double-blind (Weeks 0 - 16)
COMPLETED
|
86
|
85
|
44
|
|
Double-blind (Weeks 0 - 16)
NOT COMPLETED
|
2
|
4
|
0
|
|
Open Label 150 mg s.c. (Weeks 16 - 52)
STARTED
|
86
|
84
|
44
|
|
Open Label 150 mg s.c. (Weeks 16 - 52)
COMPLETED
|
78
|
71
|
36
|
|
Open Label 150 mg s.c. (Weeks 16 - 52)
NOT COMPLETED
|
8
|
13
|
8
|
|
Follow-up (Weeks 52 - 60)
STARTED
|
86
|
84
|
44
|
|
Follow-up (Weeks 52 - 60)
COMPLETED
|
78
|
69
|
36
|
|
Follow-up (Weeks 52 - 60)
NOT COMPLETED
|
8
|
15
|
8
|
Reasons for withdrawal
| Measure |
Secukinumab 10 mg/kg i.v. Loading
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Secukinumab 150 mg s.c. Loading
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
|---|---|---|---|
|
Double-blind (Weeks 0 - 16)
Abnormal laboratory values
|
1
|
0
|
0
|
|
Double-blind (Weeks 0 - 16)
Adverse Event
|
1
|
2
|
0
|
|
Double-blind (Weeks 0 - 16)
Withdrawal by Subject
|
0
|
2
|
0
|
|
Open Label 150 mg s.c. (Weeks 16 - 52)
Administrative problems
|
1
|
0
|
0
|
|
Open Label 150 mg s.c. (Weeks 16 - 52)
Withdrawal by Subject
|
1
|
3
|
4
|
|
Open Label 150 mg s.c. (Weeks 16 - 52)
Protocol deviation
|
0
|
1
|
0
|
|
Open Label 150 mg s.c. (Weeks 16 - 52)
Lack of Efficacy
|
3
|
3
|
3
|
|
Open Label 150 mg s.c. (Weeks 16 - 52)
Abnormal laboratory values
|
0
|
1
|
0
|
|
Open Label 150 mg s.c. (Weeks 16 - 52)
Adverse Event
|
3
|
5
|
1
|
|
Follow-up (Weeks 52 - 60)
Withdrawal by Subject
|
1
|
5
|
4
|
|
Follow-up (Weeks 52 - 60)
Administrative problems
|
1
|
0
|
0
|
|
Follow-up (Weeks 52 - 60)
Protocol deviation
|
0
|
1
|
0
|
|
Follow-up (Weeks 52 - 60)
Lack of Efficacy
|
3
|
3
|
3
|
|
Follow-up (Weeks 52 - 60)
Abnormal laboratory value
|
0
|
1
|
0
|
|
Follow-up (Weeks 52 - 60)
Adverse Event
|
3
|
5
|
1
|
Baseline Characteristics
Efficacy, Safety and Tolerability of Secukinumab in Patients With Rheumatoid Arthritis Taking Methotrexate
Baseline characteristics by cohort
| Measure |
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Total
n=221 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
53.8 Years
STANDARD_DEVIATION 11.81 • n=5 Participants
|
54.5 Years
STANDARD_DEVIATION 12.26 • n=7 Participants
|
53.5 Years
STANDARD_DEVIATION 9.33 • n=5 Participants
|
54.0 Years
STANDARD_DEVIATION 11.51 • n=4 Participants
|
|
Sex: Female, Male
Female
|
67 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
176 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
45 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
A participant was considered to be a responder according to the ACR20 criteria if the participant had at least 20% 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)/Erythrocyte Sedimentation Rate (ESR).
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20)
|
44.9 Percentage of participants
|
40.9 Percentage of participants
|
53.4 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
A participant was considered to be a responder according to the ACR50 or ACR70 criteria if the participant had at least 50% or 70% improvement, respectively, 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)/Erythrocyte Sedimentation Rate (ESR).
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Percentage of Participants Who Achieve ACR50 and ACR70
ACR50
|
18.0 Percentage of participants
|
11.4 Percentage of participants
|
20.5 Percentage of participants
|
|
Percentage of Participants Who Achieve ACR50 and ACR70
ACR70
|
5.6 Percentage of participants
|
0.0 Percentage of participants
|
8.0 Percentage of participants
|
SECONDARY outcome
Timeframe: baseline, 12 WeeksPopulation: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
The HAQ measures physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects and dollar costs. In this trial, only the disability dimension was used. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) and 3 (unable to do). Within each of the 8 categories, only the item indicating the most severe impairment contributes to the category score. The HAQ score is calculated by summing the computed scores for each category and dividing by the number of categories answered. It ranges from 0 (without any difficulty) to 3 (unable to do). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Change From Baseline in Health Assessment Questionnaire-Disease Index (HAQ-DI) Score.
|
-0.28 score on a scale
Standard Error 0.053
|
-0.17 score on a scale
Standard Error 0.074
|
-0.35 score on a scale
Standard Error 0.052
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Participants from the full analysis set (FAS), who had values at both baseline and week 12, were included in this analysis. The FAS included all participants who were randomized to study treatment.
The Disease Activity Score (DAS) is a combined index to measure disease activity in RA participants. DAS28-CRP is determined using the following variables: 28-joint counts (tender28 and swollen28), CRP, and the participant's general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 = and 100 = ). Using the data from these variables, DAS28-CRP is calculated using the following formula: DAS28-4(crp) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP+1) + 0.014\*GH + 0.96. The calculation results in a DAS28-CRP score from 0 to 10 indicating the current activity of the rheumatoid arthritis of your 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. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=82 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=43 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=85 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Change From Baseline in DAS28 Using High Sensitivity C-reactive Protein (hsCRP) (DAS28-CRP)
|
-1.65 score on a scale
Standard Error 0.120
|
-1.21 score on a scale
Standard Error 0.166
|
-1.67 score on a scale
Standard Error 0.119
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Participants from the full analysis set (FAS), who had values at both baseline and week 12, were included in this analysis. The FAS included all participants who were randomized to study treatment.
The Disease Activity Score (DAS) is a combined index to measure disease activity in RA participants. DAS28 is determined using the following variables: 28-joint counts (tender28 and swollen28), erythrocyte sedimentation rate (ESR), and the participant's general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 = and 100 = ). Using the data from these variables, DAS28-ESR is calculated using the following formula: DAS28 = 0.56 \* sqrt(tender28) + 0.28 \* sqrt(swollen28) + 0.70 \* ln(ESR) + 0.014 \* GH. The calculation results in a DAS28-ESR score from 0 to 10 indicating the current activity of the rheumatoid arthritis of your 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. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=82 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=43 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=84 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Change From Baseline in Disease Activity Score 28 Response Using ESR (DAS28-ESR)
|
-1.80 score on a scale
Standard Error 0.128
|
-1.46 score on a scale
Standard Error 0.179
|
-1.98 score on a scale
Standard Error 0.126
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
EULAR response criteria are based on DAS28 status in combination with DAS28 improvements. The EULAR response criteria are as follows: present DAS28 \<3.2 with DAS28 improvement \>1.2 corresponds to 'good response'; present DAS28 \<3.2 with DAS28 improvement between 0.6 to 1.2, or present DAS28 between 3.2 to 5.1 with DAS28 improvement from 0.6 to \>1.2, or present DAS28 \>5.2 with DAS28 improvement \>1.2 correspond to 'moderate response; present DAS28 \<3.2 with DAS28 improvement \<0.6, or present DAS28 between 3.2 to 5.1 with DAS28 improvement \<0.6, or present DAS28 \>5.1 with DAS28 improvement \<0.6 to 1.2 correspond to 'no response'.
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response
Good response
|
27.0 Percentage of participants
|
13.6 Percentage of participants
|
28.4 Percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response
Moderate response
|
44.9 Percentage of participants
|
52.3 Percentage of participants
|
46.6 Percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response
No response
|
28.1 Percentage of participants
|
34.1 Percentage of participants
|
25.0 Percentage of participants
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
The 66 joints assessed for swelling included the 8 distal interphalangeal, 10 proximal interphalangeal and 10 metacarpophalangeal joints of the hands, the 10 metatarsophalangeal and 10 proximal interphalangeal joints of the feet, the 2 wrists, 2 elbows , 2 shoulders , 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Swelling was graded present (1) or absent (0). A negative change in baseline indicates improvement.
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Change From Baseline in Swollen 66-joint Count
|
-9.81 Number of joints
Standard Error 0.612
|
-7.88 Number of joints
Standard Error 0.863
|
-9.49 Number of joints
Standard Error 0.607
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
The 68 joints assessed for tenderness included the 8 distal interphalangeal, 10 proximal interphalangeal and 10 metacarpophalangeal joints of the hands, the 10 metatarsophalangeal and 10 proximal interphalangeal joints of the feet, the 2 wrists, 2 elbows , 2 shoulders , 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 hip, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Joint tenderness was graded present (1) or absent (0). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Change From Baseline in Tender 68-joint Count
|
-11.99 Number of joints
Standard Error 1.099
|
-9.50 Number of joints
Standard Error 1.549
|
-10.31 Number of joints
Standard Error 1.093
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
The patient's assessment of pain was performed using 100 mm visual analog scale (VAS) ranging from 0 (no pain) to 100 (unbearable pain) after the question "Please indicate with a vertical mark through the horizontal line the most pain you had from your rheumatoid arthritis over the last 24 hours". A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Change From Baseline in Participant's Assessment of Rheumatoid Arthritis (RA) Pain
|
-12.60 score on a scale
Standard Error 2.071
|
-6.66 score on a scale
Standard Error 2.902
|
-14.41 score on a scale
Standard Error 2.057
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
The patient's global assessment of disease activity was performed using 100 mm VAS ranging from 0 (very good) to 100 (very poor), after the question "Considering all the ways rheumatoid arthritis affects you, please indicate with a vertical mark through the horizontal line how well you are doing today". A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Change From Baseline in Participant's Global Assessment of Disease Activity
|
-15.29 score on a scale
Standard Error 2.063
|
-9.93 score on a scale
Standard Error 2.884
|
-18.58 score on a scale
Standard Error 2.042
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
The physician's global assessment of disease activity was performed using 100 mm VAS ranging from 0 (very good) to 100 (very poor), after the question "Considering all the ways rheumatoid arthritis affects your patient, how would you rate his or her current condition?". A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Change From Baseline in Physician's Global Assessment of Disease Activity
|
-29.01 score on a scale
Standard Error 1.950
|
18.88 score on a scale
Standard Error 2.726
|
-27.05 score on a scale
Standard Error 1.925
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
Blood for this assessment was obtained to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Change From Baseline in hsCRP
|
-5.72 mg/L
Standard Error 0.946
|
-1.69 mg/L
Standard Error 1.336
|
-6.00 mg/L
Standard Error 0.938
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
Blood for this assessment was obtained to monitor disease activity and response to therapy. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Secukinumab 150 mg s.c. Loading
n=89 Participants
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 Participants
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
Secukinumab 10 mg/kg i.v. Loading
n=88 Participants
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
|---|---|---|---|
|
Change From Baseline in ESR
|
-12.43 mm/hr
Standard Error 1.425
|
-10.53 mm/hr
Standard Error 1.993
|
-16.68 mm/hr
Standard Error 1.409
|
Adverse Events
Secukinumab 10 mg/kg i.v. Loading
Secukinumab 150 mg s.c. Loading
Placebo
AIN457 Pooled Treatment Groups - Open Label Period
AIN457 Pooled Treatment Groups - Follow-up Period
Serious adverse events
| Measure |
Secukinumab 10 mg/kg i.v. Loading
n=88 participants at risk
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Secukinumab 150 mg s.c. Loading
n=89 participants at risk
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 participants at risk
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
AIN457 Pooled Treatment Groups - Open Label Period
n=214 participants at risk
Week 16 through week 52: AIN457 150 mg s.c. open label
|
AIN457 Pooled Treatment Groups - Follow-up Period
n=214 participants at risk
Follow-up period: week 52 through week 60 - AIN457 150 mg sc open label
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Cardiac disorders
Atrial fibrillation
|
1.1%
1/88
|
0.00%
0/89
|
0.00%
0/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/88
|
0.00%
0/89
|
2.3%
1/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
General disorders
Chest pain
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Infections and infestations
Pneumonia
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Infections and infestations
Sepsis
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Investigations
Arteriogram coronary
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Musculoskeletal and connective tissue disorders
Osteochondrosis
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.93%
2/214
|
0.00%
0/214
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adrenal adenoma
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.00%
0/214
|
0.47%
1/214
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm
|
0.00%
0/88
|
1.1%
1/89
|
0.00%
0/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.00%
0/214
|
0.47%
1/214
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Nervous system disorders
Lumbar radiculopathy
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Nervous system disorders
Sciatica
|
1.1%
1/88
|
0.00%
0/89
|
0.00%
0/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Psychiatric disorders
Depression
|
0.00%
0/88
|
1.1%
1/89
|
0.00%
0/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.00%
0/88
|
1.1%
1/89
|
0.00%
0/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Respiratory, thoracic and mediastinal disorders
Rheumatoid lung
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/88
|
0.00%
0/89
|
0.00%
0/44
|
0.00%
0/214
|
0.47%
1/214
|
Other adverse events
| Measure |
Secukinumab 10 mg/kg i.v. Loading
n=88 participants at risk
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Secukinumab 150 mg s.c. Loading
n=89 participants at risk
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
|
Placebo
n=44 participants at risk
placebo at Weeks 0, 1, 2, 3, 4, 8 \& 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
|
AIN457 Pooled Treatment Groups - Open Label Period
n=214 participants at risk
Week 16 through week 52: AIN457 150 mg s.c. open label
|
AIN457 Pooled Treatment Groups - Follow-up Period
n=214 participants at risk
Follow-up period: week 52 through week 60 - AIN457 150 mg sc open label
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/88
|
2.2%
2/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/88
|
2.2%
2/89
|
0.00%
0/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
0.00%
0/88
|
0.00%
0/89
|
2.3%
1/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/88
|
0.00%
0/89
|
2.3%
1/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Gastrointestinal disorders
Constipation
|
1.1%
1/88
|
0.00%
0/89
|
2.3%
1/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Gastrointestinal disorders
Diarrhoea
|
1.1%
1/88
|
1.1%
1/89
|
0.00%
0/44
|
2.3%
5/214
|
0.00%
0/214
|
|
Gastrointestinal disorders
Dyspepsia
|
1.1%
1/88
|
2.2%
2/89
|
0.00%
0/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Gastrointestinal disorders
Nausea
|
2.3%
2/88
|
1.1%
1/89
|
0.00%
0/44
|
0.93%
2/214
|
0.00%
0/214
|
|
Immune system disorders
Immunodeficiency
|
0.00%
0/88
|
0.00%
0/89
|
2.3%
1/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Infections and infestations
Cystitis
|
0.00%
0/88
|
2.2%
2/89
|
0.00%
0/44
|
0.93%
2/214
|
0.00%
0/214
|
|
Infections and infestations
Erythema migrans
|
0.00%
0/88
|
0.00%
0/89
|
2.3%
1/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Infections and infestations
Gastroenteritis
|
2.3%
2/88
|
1.1%
1/89
|
2.3%
1/44
|
1.4%
3/214
|
0.00%
0/214
|
|
Infections and infestations
Influenza
|
0.00%
0/88
|
1.1%
1/89
|
2.3%
1/44
|
1.9%
4/214
|
0.00%
0/214
|
|
Infections and infestations
Laryngitis
|
1.1%
1/88
|
2.2%
2/89
|
0.00%
0/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Infections and infestations
Nasopharyngitis
|
5.7%
5/88
|
5.6%
5/89
|
9.1%
4/44
|
5.1%
11/214
|
0.47%
1/214
|
|
Infections and infestations
Oral herpes
|
0.00%
0/88
|
1.1%
1/89
|
6.8%
3/44
|
2.3%
5/214
|
0.00%
0/214
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/88
|
1.1%
1/89
|
0.00%
0/44
|
2.8%
6/214
|
0.47%
1/214
|
|
Infections and infestations
Rhinitis
|
2.3%
2/88
|
0.00%
0/89
|
4.5%
2/44
|
1.4%
3/214
|
0.00%
0/214
|
|
Infections and infestations
Upper respiratory tract infection
|
1.1%
1/88
|
1.1%
1/89
|
0.00%
0/44
|
7.9%
17/214
|
0.47%
1/214
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/88
|
2.2%
2/89
|
2.3%
1/44
|
1.4%
3/214
|
0.00%
0/214
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/88
|
1.1%
1/89
|
2.3%
1/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/88
|
2.2%
2/89
|
0.00%
0/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.00%
0/88
|
1.1%
1/89
|
4.5%
2/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/88
|
0.00%
0/89
|
2.3%
1/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/88
|
1.1%
1/89
|
2.3%
1/44
|
0.47%
1/214
|
0.93%
2/214
|
|
Musculoskeletal and connective tissue disorders
Fibromyalgia
|
0.00%
0/88
|
2.2%
2/89
|
0.00%
0/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/88
|
5.6%
5/89
|
4.5%
2/44
|
5.6%
12/214
|
2.3%
5/214
|
|
Musculoskeletal and connective tissue disorders
Spinal pain
|
1.1%
1/88
|
1.1%
1/89
|
2.3%
1/44
|
2.3%
5/214
|
0.00%
0/214
|
|
Nervous system disorders
Headache
|
2.3%
2/88
|
4.5%
4/89
|
2.3%
1/44
|
2.3%
5/214
|
0.00%
0/214
|
|
Nervous system disorders
Sciatica
|
2.3%
2/88
|
0.00%
0/89
|
0.00%
0/44
|
0.93%
2/214
|
0.00%
0/214
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/88
|
0.00%
0/89
|
2.3%
1/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Psychiatric disorders
Mood altered
|
0.00%
0/88
|
0.00%
0/89
|
2.3%
1/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/88
|
1.1%
1/89
|
2.3%
1/44
|
1.4%
3/214
|
0.00%
0/214
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.1%
1/88
|
0.00%
0/89
|
2.3%
1/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/88
|
1.1%
1/89
|
0.00%
0/44
|
3.3%
7/214
|
0.00%
0/214
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.3%
2/88
|
0.00%
0/89
|
0.00%
0/44
|
1.4%
3/214
|
0.00%
0/214
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal erythema
|
0.00%
0/88
|
0.00%
0/89
|
2.3%
1/44
|
0.47%
1/214
|
0.00%
0/214
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/88
|
1.1%
1/89
|
2.3%
1/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.1%
1/88
|
1.1%
1/89
|
2.3%
1/44
|
0.00%
0/214
|
0.00%
0/214
|
|
Vascular disorders
Hypertension
|
1.1%
1/88
|
2.2%
2/89
|
2.3%
1/44
|
5.1%
11/214
|
0.00%
0/214
|
|
Vascular disorders
Varicose vein
|
0.00%
0/88
|
0.00%
0/89
|
2.3%
1/44
|
0.00%
0/214
|
0.00%
0/214
|
Additional Information
Study Director
Novartis Pharmaceuticals
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