Spondyloarthritis
Conditions
Keywords
axial spondyloarthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, inflammatory back pain, spinal pain, secukinumab, AIN457
Brief summary
The purpose of the study was to evaluate the efficacy and safety of secukinumab 150 mg compared to placebo in the early management (Baseline to Week 8) of spinal pain, disease activity, fatigue, and predictability of disease flares in patients with axial spondyloarthritis (axSpA) who had an inadequate response to prior non-steroidal anti-inflammatory drugs (NSAIDs). This study also explored the efficacy and safety of secukinumab 300 mg compared to secukinumab 150 mg from Week 8 to Week 24 in order to assess the potential additional benefits of dose escalation in patients with axSpA.
Detailed description
The study consisted of 2 treatment periods: a double-blind, placebo-controlled period from Baseline to Week 8 (Treatment Period 1) and a double-blind secukinumab treatment period from Week 8 to Week 24 (Treatment Period 2). At Baseline (Treatment Period 1), patients were randomized in a 3:1 ratio to either secukinumab 150 mg (Group A) or placebo (Group B). At Week 8 (Treatment Period 2), patients were re-randomized and re-assigned respectively to 1 of 5 treatment arms to receive either secukinumab 150 mg or secukinumab 300 mg. Patients assigned to secukinumab 150 mg (Group A) at Baseline who were responders (i.e. spinal pain score \< 4) at Week 8 continued on the same dose until Week 24 under 1 treatment arm (Arm A1). Patients assigned to secukinumab 150 mg at Baseline who were non-responders at Week 8 were re-randomized to 1 of 2 treatment arms: secukinumab 150 mg (Arm A2) or secukinumab 300 mg (Arm A3) from Week 8 to Week 24. Similarly, patients assigned to placebo (Group B) at Baseline were re-randomized to 1 of 2 treatment arms: secukinumab 150 mg (Arm B1) or secukinumab 300 mg (Arm B2) from Week 8 until Week 24.
Interventions
BIOLOGICALAIN457
anti IL-17a monoclonal antibody
DRUGAIN457 Placebo
Placebo matching AIN457
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of axial spondylarthritis (axSpA, either ankylosing spondylitis or non radiographic axial spondylarthritis) according to ASAS axSpA classification criteria * patients with back pain for at least 3 months and age of onset less than 45 years * Active axSpA as assessed by total BASDAI score of at least 4 at Baseline. * Spinal pain numeric rating scale score of more than 4 at Baseline. * inadequate response to or failure to respond to at least 2 different NSAIDs at the highest recommended dose for at least 4 weeks in total prior to randomization Key
Exclusion criteria
* Chest X-ray or MRI with evidence of ongoing infectious or malignant process * Patients previously treated with any biological immunomodulating agents, except those targeting tumor necrosis factor alpha. * Patients who have been exposed to more than one anti-tumor necrosis factor alpha agent. * Active ongoing inflammatory diseases other than axial spondyloarthritis * Other ongoing mechanical diseases affecting the spine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Week 8 | The spinal pain numerical rating scale (NRS) is an 11-point scale to assess pain intensity in patients who are able to self-report. It is an 11-point scale from 0-10: 1) 0 = no pain. 2) 10 = the most intense pain imaginable. To calculate the average spinal pain, the patient was asked to answer 2 questions to get 2 pain ratings, the total spinal pain corresponding to the intensity of spinal pain experienced on an average over 24 hours during the previous week and the nocturnal back pain corresponding to the intensity of spinal pain experienced on an average over the night during the previous week. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Bath Ankylosing Spondylitis Disease Activity Index Score Below 4 at Week 8 (Treatment Period 1) | Week 8 | The Bath ankylosing spondylitis disease activity index (BASDAI) consists of a 0 through 10 scale, which is used to answer 6 questions pertaining to the 5 major symptoms of ankylosing spondylitis. To give each symptom equal weighting, the mean (average) of the 2 scores relating to morning stiffness (questions 5 and 6) is taken. The mean of questions 5 and 6 is added to the scores from questions 1-4. The resulting 0 to 50 score is divided by 5 to give a final 0 - 10 BASDAI score. |
Countries
Belgium, Bulgaria, Croatia, Czechia, Estonia, Finland, Greece, Ireland, Italy, Latvia, Lithuania, Poland, Russia, Spain, Sweden, Switzerland, United Kingdom
Participant flow
Recruitment details
This study was conducted at 66 centers in 17 countries worldwide: Spain(14), Czech Republic(3), Finland(2), Lithuania(2), Estonia(3), Latvia(3), Switzerland(1), Russia(4), Sweden(4), United Kingdom(5), Belgium(2), Ireland(2), Poland(7), Croatia(3), Bulgaria(5), Greece(5), Italy(1).
Pre-assignment details
At Baseline, patients were randomized to either secukinumab 150 mg or placebo (Group A or B). At Week 8, patients were re-randomized or re-assigned respectively to 1 of 5 treatment arms to receive either secukinumab 150 mg or secukinumab 300 mg (Arm A1 to B2).
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 150 mg (Group A) Treatment Period 1: Secukinumab 150 mg (1 x 1.0 mL) s.c. administered at Baseline, Week 1, 2, 3 and 4 | 285 |
| Placebo (Group B) Treatment Period 1: Placebo (1 x 1.0 mL) s.c. administered at Baseline and Week 1, 2, 3 and 4 | 95 |
| Arm A1 Treatment Period 2: Secukinumab 150 mg (1 x 1.0 mL) plus placebo (1 x 1.0 mL) administered at Week 8, 12, 16 and 20 | 0 |
| Arm A2 Treatment Period 2: Secukinumab 150 mg (1 x 1.0 mL) plus placebo (1 x 1.0 mL) administered at Week 8, 12, 16 and 20 | 0 |
| Arm A3 Treatment Period 2: Secukinumab 300 mg (2 x 1.0 mL) administered at Week 8, 12, 16, and 20 | 0 |
| Arm B1 Treatment Period 2: Secukinumab 150 mg (1 x 1.0 mL) plus placebo (1 x 1.0 mL) administered at Week 8, 12, 16 and 20 | 0 |
| Arm B2 Treatment Period 2: Secukinumab 300 mg (2 x 1.0 mL) administered at Week 8, 12, 16, and 20 | 0 |
| Total | 380 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (TP1)(Baseline-Wk 8) | Adverse Event | 3 | 2 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (TP1)(Baseline-Wk 8) | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (TP1)(Baseline-Wk 8) | Protocol Deviation | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (TP1)(Baseline-Wk 8) | Subject/Guardian Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (TP1)(Baseline-Wk 8) | Withdrawal of Informed Consent | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 2 (TP2) (Wk 8-Wk 24) | Adverse Event | 0 | 0 | 0 | 1 | 2 | 0 | 1 |
| Treatment Period 2 (TP2) (Wk 8-Wk 24) | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 2 (TP2) (Wk 8-Wk 24) | Withdrawal of Informed Consent | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Secukinumab 150 mg (Group A) | Placebo (Group B) | Total |
|---|---|---|---|
| Age, Continuous | 42.3 Years STANDARD_DEVIATION 11.88 | 40.9 Years STANDARD_DEVIATION 12.2 | 42.0 Years STANDARD_DEVIATION 11.96 |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Caucasian | 267 Participants | 93 Participants | 360 Participants |
| Race/Ethnicity, Customized Other | 16 Participants | 1 Participants | 17 Participants |
| Sex: Female, Male Female | 106 Participants | 39 Participants | 145 Participants |
| Sex: Female, Male Male | 179 Participants | 56 Participants | 235 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 285 | 0 / 95 | 0 / 90 | 0 / 94 | 0 / 94 | 0 / 45 | 0 / 44 |
| other Total, other adverse events | 59 / 285 | 23 / 95 | 21 / 90 | 24 / 94 | 23 / 94 | 9 / 45 | 13 / 44 |
| serious Total, serious adverse events | 4 / 285 | 0 / 95 | 3 / 90 | 1 / 94 | 1 / 94 | 0 / 45 | 0 / 44 |
Outcome results
Primary
Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1)
The spinal pain numerical rating scale (NRS) is an 11-point scale to assess pain intensity in patients who are able to self-report. It is an 11-point scale from 0-10: 1) 0 = no pain. 2) 10 = the most intense pain imaginable. To calculate the average spinal pain, the patient was asked to answer 2 questions to get 2 pain ratings, the total spinal pain corresponding to the intensity of spinal pain experienced on an average over 24 hours during the previous week and the nocturnal back pain corresponding to the intensity of spinal pain experienced on an average over the night during the previous week.
Time frame: Week 8
Population: Full Analysis Set (FAS) in Treatment Period 1.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Secukinumab 150 mg (Group A) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Average Spinal Pain Score | Yes | 91 Participants |
| Secukinumab 150 mg (Group A) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Average Spinal Pain Score | No | 188 Participants |
| Secukinumab 150 mg (Group A) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Total Spinal Pain Score | Yes | 77 Participants |
| Secukinumab 150 mg (Group A) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Total Spinal Pain Score | No | 202 Participants |
| Secukinumab 150 mg (Group A) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Nocturnal Spinal Pain Score | Yes | 92 Participants |
| Secukinumab 150 mg (Group A) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Nocturnal Spinal Pain Score | No | 187 Participants |
| Placebo (Group B) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Nocturnal Spinal Pain Score | Yes | 16 Participants |
| Placebo (Group B) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Average Spinal Pain Score | Yes | 19 Participants |
| Placebo (Group B) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Total Spinal Pain Score | No | 75 Participants |
| Placebo (Group B) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Average Spinal Pain Score | No | 73 Participants |
| Placebo (Group B) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Nocturnal Spinal Pain Score | No | 76 Participants |
| Placebo (Group B) | Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | Total Spinal Pain Score | Yes | 17 Participants |
Comparison: Average Spinal Pain Score \<4 at Week 8p-value: 0.026495% CI: [1.08, 3.33]Regression, Logistic
Comparison: Total Spinal Pain Score \<4 at Week 8p-value: 0.07295% CI: [0.95, 3.1]Regression, Logistic
Comparison: Nocturnal Spinal Pain Scorep-value: 0.004395% CI: [1.31, 4.31]Regression, Logistic
Secondary
Percentage of Participants With a Bath Ankylosing Spondylitis Disease Activity Index Score Below 4 at Week 8 (Treatment Period 1)
The Bath ankylosing spondylitis disease activity index (BASDAI) consists of a 0 through 10 scale, which is used to answer 6 questions pertaining to the 5 major symptoms of ankylosing spondylitis. To give each symptom equal weighting, the mean (average) of the 2 scores relating to morning stiffness (questions 5 and 6) is taken. The mean of questions 5 and 6 is added to the scores from questions 1-4. The resulting 0 to 50 score is divided by 5 to give a final 0 - 10 BASDAI score.
Time frame: Week 8
Population: Full Analysis Set (FAS) in Treatment Period 1.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Secukinumab 150 mg (Group A) | Percentage of Participants With a Bath Ankylosing Spondylitis Disease Activity Index Score Below 4 at Week 8 (Treatment Period 1) | Yes (n=95,22) | 95 Participants |
| Secukinumab 150 mg (Group A) | Percentage of Participants With a Bath Ankylosing Spondylitis Disease Activity Index Score Below 4 at Week 8 (Treatment Period 1) | No (n=185,70) | 185 Participants |
| Placebo (Group B) | Percentage of Participants With a Bath Ankylosing Spondylitis Disease Activity Index Score Below 4 at Week 8 (Treatment Period 1) | No (n=185,70) | 70 Participants |
| Placebo (Group B) | Percentage of Participants With a Bath Ankylosing Spondylitis Disease Activity Index Score Below 4 at Week 8 (Treatment Period 1) | Yes (n=95,22) | 22 Participants |
Comparison: BASDAI Score \<4 at Week 8p-value: 0.046695% CI: [1.01, 3.04]Regression, Logistic