Ankylosing Spondylitis
Conditions
Keywords
Ankylosing Spondylitis, secukinumab, AIN457H, SpondyloArthritis
Brief summary
The purpose of this study was to assess the clinical efficacy, safety and tolerability of secukinumab subcutaneous injections up to 52 weeks in Japanese patients with active AS despite current or previous non-steroidal anti-inflammatory drugs (NSAIDs) and/or anti-tumor necrosis factor (TNF) α therapy. Efficacy and safety data were used to support the registration of secukinumab in Japan for the treatment of active AS.
Interventions
DRUGSecukinumab 150 mg provided in 1.0 mL pre-filled syringes (PFSs) for sc injection.
Baseline, 1, 2, 3, 4 week. After 4 week, administered every 4 weeks.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of moderate to severe AS with prior documented radiologic evidence (x-ray or radiologist's report) fulfilling the Modified New York criteria for AS with active AS assessed by BASDAI ≥ 4 (0-10) and spinal pain as measured by VAS≥ 4 cm (BASDAI question #2) at Baseline * Patients should have been on NSAIDs at the highest recommended dose for at least 3 months prior to baseline with an inadequate response or failure to respond, or less than 3 months if therapy had to be withdrawn due to intolerance, toxicity or contraindications * Patients who have been on a TNFα inhibitor (not more than one) must have experienced an inadequate response to previous or current treatment given at an approved dose for at least 3 months prior to baseline or have been intolerant to at least one administration of an anti-TNFα agent
Exclusion criteria
* Patients with total ankylosis of the spine * Patients previously treated with any biological immunomodulating agents except for those targeting TNFα * Active ongoing inflammatory diseases other than AS that might confound the evaluation of the benefit of secukinumab therapy, including inflammatory bowel disease or uveitis * Known infection with HIV, hepatitis B or hepatitis C at screening or baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of SpondyloArthritis International Society 20 Response (ASAS20) | week 16 | This table is ASAS20 response using non-responder imputation for FAS It assesses the efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline in Japanese patients with active AS based on the proportion of patients achieving an ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response. The ASAS Response Criteria (ASAS 20) is defined as an improvement of ≥ 20% and ≥ 1 unit on a scale of 10 in at least three of the four main domains and no worsening of ≥ 20% and ≥ 1 unit on a scale of 10 in the remaining domain |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bath Ankylosing Spondylitis Disease Activity (BASDAI) 50 Response Rate | Week 16 | The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients achieving Bath Ankylosing Spondylitis Disease Activity (BASDAI) 50 response The BASDAI 50 is defined as an improvement of at least 50% in the BASDAI compared to baseline |
| Change in High Sensitivity C-Reactive Protein (hsCRP) | baseline, Week 16 | hsCRP (mg/L) change from baseline using observed data with log e transformation The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline of high sensitivity C-Reactive Protein (hsCRP) hsCRP is measured as a marker of inflammation from blood samples during the study |
| Number of Participants With ASAS 5/6 Response Criteria | Week 16 | The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients meeting the ASAS 5/6 response criteria The ASAS 5/6 improvement criteria is an improvement of ≥20% in at least five of all six domains |
| Mean Change From Baseline in BASDAI From Baseline | Baseline, week 16 | The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline in total BASDAI The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) in response to six questions asked of the patient pertaining to the five major symptoms of AS Each question (question 1 to 6) is scored from 0 to 10 (0 being no problem and 10 being the worst problem). To give each symptom equal weighting, the mean (average) of the two 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. |
| Change From Baseline in Short Form Health Survey Physical Component Summary (SF-36 PCS) Score | Baseline, week 16 | SF-36 PCS, mean change from baseline: The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline in Short Form Health Survey Physical Component Summary (SF-36 PCS) The SF-36 is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions Score range is from 0 (no problems) to 100 (unable to perform the activity) SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS is used to assess improvement from baseline. There is no total overall score; scoring is computed for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. |
| Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score | Baseline, week 16 | The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) The ASQoL is a self-administered questionnaire designed to assess health-related quality of life in adult patients with Ankylosing Spondylitis. The ASQoL contains 18 items with a dichotomous yes/no response option. A single point is assigned for each yes response and no points for each no response resulting in overall scores that range from 0 (least severity) to 18 (highest severity) |
| Proportion of Participants Achieving ASAS Partial Remission | week 16 | The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients achieving an ASAS partial remission The ASAS partial remission criteria are defined as a value not above 2 units in each of the four main domains on a scale of 10 |
| ASAS 40 Response Rate With Non-responder Imputation (NRI) | Week 16 | The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients achieving an ASAS 40 response ASAS40 response is defined as an improvement of ≥40% and ≥2 units on a scale of 10 in at least three of the four ASAS main domains and no worsening at all in the remaining domain |
| Number of Participants With Immunogenicity Against Secukinumab | week 60 | Concentration of anti-secukinumab antibodies Assessment of immunogenicity against secukinumab by concentration of anti-secukinumab antibodies at pre-dose. An electrochemiluminescence method was used for the detection of potential anti-secukinumab antibody formation. |
| Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | week 60 | Common Terminology Criteria for Adverse Events (CTCAE) Grades 1-5 refer to severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)\*. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL\*\*. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. \*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. \*\*Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. |
| Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | week 60 | Common Terminology Criteria for Adverse Events (CTCAE) Grades 1-5 refer to severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)\*. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL\*\*. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. \*Instrumental ADL include preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. \*\*Self care ADL include bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. |
| Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | week 60 | During the entire safety reporting period, mean values of each liver enzyme parameter stayed within the normal range and were comparable to the baseline values ALP=Alkaline phosphatase ALT=Alanine aminotransferase AST=Aspartate aminotransferase TBL=Total bilirubin ULN=Upper Limit Normal |
| Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | week 60 | During the entire safety reporting period, mean values of each lipid parameter stayed within the normal range and were comparable to the baseline values |
| Participants With Newly Occurring Notable Abnormalities in Vital Signs | week 60 | Sitting Pulse (bpm) High only (\> 100 bpm) Low only (\< 60 bpm) Low and High (\< 60 bpm and \> 100 bpm) Sitting Diastolic Blood Pressure (BP) (mmHg) High only (≥ 90 mmHg) Low only (\< 60 mmHg) Low and High (\< 60 mmHg and ≥ 90 mmHg) Sitting Systolic Blood Pressure (mmHg) High only (≥ 140 mmHg) Low only (\< 90 mmHg) Low and High (\< 90 mmHg and ≥ 140 mmHg) |
| Change in Serum Concentration of Secukinumab | Baseline, weeks 4, 16, 24, 52, 60 | The assessment of pre dose concentration of secukinumab in Japanese AS patients An enzyme-linked immunosorbent assay (ELISA) method will be used for bioanalytical analysis of secukinumab in serum, with an anticipated lower limit of quantification (LLOQ) of 80 ng/mL. |
Countries
Japan
Participant flow
Recruitment details
A total of 37 patients were screened, and 30 patients (81.1%) completed the screening phase and entered Treatment Period
Pre-assignment details
Seven patients were screening failures
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 150mg A screening (SCR) epoch ran 4-10 weeks before baseline (BSL) and was used to assess eligibility followed by 52 weeks of treatment. The treatment periods consisted of Treatment period 1 (BSL to Week 24) and Treatment period 2 (Week 24 to Week 52). After Week 52 there was a post-treatment follow-up until Week 60. A follow-up visit was done at 12 weeks after last study treatment administration for all patients, regardless of whether they completed the entire study as planned (Week 60) or discontinued prematurely. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lack of Efficacy | 2 |
Baseline characteristics
| Characteristic | Secukinumab 150mg |
|---|---|
| Age, Continuous | 44.0 years STANDARD_DEVIATION 13.25 |
| Age, Customized <65 years | 27 Participants |
| Age, Customized >=65years | 3 Participants |
| Age, Customized >=75 years | 0 Participants |
| Race/Ethnicity, Customized Asian | 30 participants |
| Race/Ethnicity, Customized Other | 0 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 26 / 30 |
| serious Total, serious adverse events | 3 / 30 |
Outcome results
Primary
Assessment of SpondyloArthritis International Society 20 Response (ASAS20)
This table is ASAS20 response using non-responder imputation for FAS It assesses the efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline in Japanese patients with active AS based on the proportion of patients achieving an ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response. The ASAS Response Criteria (ASAS 20) is defined as an improvement of ≥ 20% and ≥ 1 unit on a scale of 10 in at least three of the four main domains and no worsening of ≥ 20% and ≥ 1 unit on a scale of 10 in the remaining domain
Time frame: week 16
Population: Full analysis set (FAS): The FAS comprised of all patients who entered into the treatment periods.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 150mg | Assessment of SpondyloArthritis International Society 20 Response (ASAS20) | 21 participants |
Secondary
ASAS 40 Response Rate With Non-responder Imputation (NRI)
The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients achieving an ASAS 40 response ASAS40 response is defined as an improvement of ≥40% and ≥2 units on a scale of 10 in at least three of the four ASAS main domains and no worsening at all in the remaining domain
Time frame: Week 16
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 150mg | ASAS 40 Response Rate With Non-responder Imputation (NRI) | 14 participants |
Secondary
Bath Ankylosing Spondylitis Disease Activity (BASDAI) 50 Response Rate
The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients achieving Bath Ankylosing Spondylitis Disease Activity (BASDAI) 50 response The BASDAI 50 is defined as an improvement of at least 50% in the BASDAI compared to baseline
Time frame: Week 16
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 150mg | Bath Ankylosing Spondylitis Disease Activity (BASDAI) 50 Response Rate | 11 participants |
Secondary
Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score
The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) The ASQoL is a self-administered questionnaire designed to assess health-related quality of life in adult patients with Ankylosing Spondylitis. The ASQoL contains 18 items with a dichotomous yes/no response option. A single point is assigned for each yes response and no points for each no response resulting in overall scores that range from 0 (least severity) to 18 (highest severity)
Time frame: Baseline, week 16
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 150mg | Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score | -3.40 scores on a scale | Standard Deviation 4 |
Secondary
Change From Baseline in Short Form Health Survey Physical Component Summary (SF-36 PCS) Score
SF-36 PCS, mean change from baseline: The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline in Short Form Health Survey Physical Component Summary (SF-36 PCS) The SF-36 is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions Score range is from 0 (no problems) to 100 (unable to perform the activity) SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS is used to assess improvement from baseline. There is no total overall score; scoring is computed for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score.
Time frame: Baseline, week 16
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 150mg | Change From Baseline in Short Form Health Survey Physical Component Summary (SF-36 PCS) Score | 6.306 scores on a scale | Standard Deviation 8.0724 |
Secondary
Change in High Sensitivity C-Reactive Protein (hsCRP)
hsCRP (mg/L) change from baseline using observed data with log e transformation The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline of high sensitivity C-Reactive Protein (hsCRP) hsCRP is measured as a marker of inflammation from blood samples during the study
Time frame: baseline, Week 16
Population: FAS
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Secukinumab 150mg | Change in High Sensitivity C-Reactive Protein (hsCRP) | 0.247 mg/L |
Secondary
Change in Serum Concentration of Secukinumab
The assessment of pre dose concentration of secukinumab in Japanese AS patients An enzyme-linked immunosorbent assay (ELISA) method will be used for bioanalytical analysis of secukinumab in serum, with an anticipated lower limit of quantification (LLOQ) of 80 ng/mL.
Time frame: Baseline, weeks 4, 16, 24, 52, 60
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab 150mg | Change in Serum Concentration of Secukinumab | week 4 | 51.3 μg/mL | Standard Deviation 15.35 |
| Secukinumab 150mg | Change in Serum Concentration of Secukinumab | week 16 | 25.0 μg/mL | Standard Deviation 10.19 |
| Secukinumab 150mg | Change in Serum Concentration of Secukinumab | week 24 | 22.2 μg/mL | Standard Deviation 8.96 |
| Secukinumab 150mg | Change in Serum Concentration of Secukinumab | week 52 | 21.1 μg/mL | Standard Deviation 6.08 |
| Secukinumab 150mg | Change in Serum Concentration of Secukinumab | week 60 | 6.2 μg/mL | Standard Deviation 3.61 |
Secondary
Mean Change From Baseline in BASDAI From Baseline
The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline in total BASDAI The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) in response to six questions asked of the patient pertaining to the five major symptoms of AS Each question (question 1 to 6) is scored from 0 to 10 (0 being no problem and 10 being the worst problem). To give each symptom equal weighting, the mean (average) of the two 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: Baseline, week 16
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 150mg | Mean Change From Baseline in BASDAI From Baseline | -3.088 scores on a scale | Standard Deviation 2.0697 |
Secondary
Number of Participants With ASAS 5/6 Response Criteria
The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients meeting the ASAS 5/6 response criteria The ASAS 5/6 improvement criteria is an improvement of ≥20% in at least five of all six domains
Time frame: Week 16
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 150mg | Number of Participants With ASAS 5/6 Response Criteria | 14 participants |
Secondary
Number of Participants With Immunogenicity Against Secukinumab
Concentration of anti-secukinumab antibodies Assessment of immunogenicity against secukinumab by concentration of anti-secukinumab antibodies at pre-dose. An electrochemiluminescence method was used for the detection of potential anti-secukinumab antibody formation.
Time frame: week 60
Population: The safety set included all patients who took at least one dose of study treatment during the treatment periods.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 150mg | Number of Participants With Immunogenicity Against Secukinumab | 0 participants |
Secondary
Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade
Common Terminology Criteria for Adverse Events (CTCAE) Grades 1-5 refer to severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)\*. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL\*\*. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. \*Instrumental ADL include preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. \*\*Self care ADL include bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.
Time frame: week 60
Population: safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Alkaline Phosphatase (U/L), Serum (Grade1) | 3 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Alkaline Phosphatase (U/L), Serum (Grade2) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Alkaline Phosphatase (U/L), Serum (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Alkaline Phosphatase (U/L), Serum (Grade4) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Alanine Aminotransferase (U/L), Serum (Grade1) | 3 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Alanine Aminotransferase (U/L), Serum (Grade2) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Alanine Aminotransferase (U/L), Serum (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Alanine Aminotransferase (U/L), Serum (Grade4) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Aspartate Aminotransferase (U/L), Serum (Grade1) | 4 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Aspartate Aminotransferase (U/L), Serum (Grade2) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Aspartate Aminotransferase (U/L), Serum (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Aspartate Aminotransferase (U/L), Serum (Grade4) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Bilirubin (umol/L), Serum (Grade1) | 2 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Bilirubin (umol/L), Serum (Grade2) | 1 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Bilirubin (umol/L), Serum (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Bilirubin (umol/L), Serum (Grade4) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Cholesterol (mmol/L), Serum (Grade1) Serum | 4 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Cholesterol (mmol/L), Serum (Grade2) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Cholesterol (mmol/L), Serum (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Cholesterol (mmol/L), Serum (Grade4) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Creatinine (umol/L), Plasma/Serum (Grade1) | 1 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Creatinine (umol/L), Plasma/Serum (Grade2) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Creatinine (umol/L), Plasma/Serum (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Creatinine (umol/L), Plasma/Serum (Grade4) Serum | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Gamma Glutamyl Transferase (U/L), Serum (Grade1) | 1 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Gamma Glutamyl Transferase (U/L), Serum (Grade2) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Gamma Glutamyl Transferase (U/L), Serum (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Gamma Glutamyl Transferase (U/L), Serum (Grade4) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Glucose Decreased (mmol/L), Plasma (Grade1) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Glucose Decreased (mmol/L), Plasma (Grade2) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Glucose Decreased (mmol/L), Plasma (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Glucose Decreased (mmol/L), Plasma (Grade4) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Glucose Increased (mmol/L), Plasma (Grade1) | 12 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Glucose Increased (mmol/L), Plasma (Grade2) | 3 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Glucose Increased (mmol/L), Plasma (Grade3) | 1 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Glucose Increased (mmol/L), Plasma (Grade4) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Triglycerides (mmol/L), Plasma/Serum (Grade1) | 9 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Triglycerides (mmol/L), Plasma/Serum (Grade2) | 1 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Triglycerides (mmol/L), Plasma/Serum (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade | Triglycerides (mmol/L), Plasma/Serum (Grade4) | 0 participants |
Secondary
Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood
Common Terminology Criteria for Adverse Events (CTCAE) Grades 1-5 refer to severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)\*. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL\*\*. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. \*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. \*\*Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.
Time frame: week 60
Population: The safety set included all patients who took at least one dose of study treatment during the treatment periods.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Hemoglobin (g/L) <LLN - 100 g/L (Grade1) | 6 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Hemoglobin (g/L) <100 - 80 g/L (Grade2) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Hemoglobin (g/L) < 80g/L (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Lymphocytes (10E9/L) <LLN - 0.8 × 10e9/L (Grade1) | 2 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Lymphocytes (10E9/L) <0.8 - 0.5 × 10e9/L (Grade2) | 1 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Lymphocytes (10E9/L) <0.5 - 0.2 × 10e9/L (Grade3) | 1 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Lymphocytes (10E9/L) <0.2 × 10e9/L (Grade4) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Neutrophils (10E9/L) < LLN - 1.5 × 10e9/L (Grade1) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Platelets (10E9/L) <LLN - 75.0 ×10e9/L (Grade1) | 3 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Neutrophils (10E9/L) < 1.5 - 1.0 × 10e9/L (Grade2) | 1 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Neutrophils (10E9/L) < 1.0 - 0.5 × 10e9/L (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Neutrophils (10E9/L) < 0.5 × 10e9/L (Grade4) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Platelets (10E9/L) <75.0 - 50.0 ×10e9/L (Grade2) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Platelets (10E9/L) <50.0 - 25.0 ×10e9/L (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Platelets (10E9/L), Blood <25.0 ×10e9/L (Grade4) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Leukocytes (10E9/L) <LLN - 3.0 × 10e9/L (Grade1) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Leukocytes (10E9/L) <3.0 - 2.0 × 10e9/L (Grade2) | 1 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Leukocytes (10E9/L) <2.0 - 1.0 × 10e9/L (Grade3) | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood | Leukocytes (10E9/L) <1.0 × 10e9/L (Grade4) | 0 participants |
Secondary
Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities
During the entire safety reporting period, mean values of each lipid parameter stayed within the normal range and were comparable to the baseline values
Time frame: week 60
Population: safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | LDL: > 2.5 × ULN | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | HDL: ≤ LLN | 5 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | HDL: < 0.8 × LLN | 1 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | LDL: ≥ ULN | 1 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | LDL: > 1.5 × ULN | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | Cholesterol: ≥ ULN | 4 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | Cholesterol: > 1.5 × ULN | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | Cholesterol: > 2.5 × ULN | 0 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | Triglycerides: ≥ ULN | 8 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | Triglycerides: > 1.5 × ULN | 4 participants |
| Secukinumab 150mg | Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities | Triglycerides: > 2.5 × ULN | 0 participants |
Secondary
Participants With Newly Occurring Notable Abnormalities in Vital Signs
Sitting Pulse (bpm) High only (\> 100 bpm) Low only (\< 60 bpm) Low and High (\< 60 bpm and \> 100 bpm) Sitting Diastolic Blood Pressure (BP) (mmHg) High only (≥ 90 mmHg) Low only (\< 60 mmHg) Low and High (\< 60 mmHg and ≥ 90 mmHg) Sitting Systolic Blood Pressure (mmHg) High only (≥ 140 mmHg) Low only (\< 90 mmHg) Low and High (\< 90 mmHg and ≥ 140 mmHg)
Time frame: week 60
Population: safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab 150mg | Participants With Newly Occurring Notable Abnormalities in Vital Signs | Sitting Diastolic BP (mmHg), High only | 8 participants |
| Secukinumab 150mg | Participants With Newly Occurring Notable Abnormalities in Vital Signs | Sitting Pulse (bpm) High only | 2 participants |
| Secukinumab 150mg | Participants With Newly Occurring Notable Abnormalities in Vital Signs | Sitting Pulse (bpm) Low only | 5 participants |
| Secukinumab 150mg | Participants With Newly Occurring Notable Abnormalities in Vital Signs | Sitting Pulse (bpm) Low and High | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring Notable Abnormalities in Vital Signs | Sitting Diastolic BP (mmHg), Low only | 5 participants |
| Secukinumab 150mg | Participants With Newly Occurring Notable Abnormalities in Vital Signs | Sitting Diastolic BP (mmHg), Low and high | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring Notable Abnormalities in Vital Signs | Sitting Systolic BP (mmHg) High only | 12 participants |
| Secukinumab 150mg | Participants With Newly Occurring Notable Abnormalities in Vital Signs | Sitting Systolic BP (mmHg) Low only | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring Notable Abnormalities in Vital Signs | Sitting Systolic BP (mmHg) Low and High | 0 participants |
Secondary
Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities
During the entire safety reporting period, mean values of each liver enzyme parameter stayed within the normal range and were comparable to the baseline values ALP=Alkaline phosphatase ALT=Alanine aminotransferase AST=Aspartate aminotransferase TBL=Total bilirubin ULN=Upper Limit Normal
Time frame: week 60
Population: safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT > 3 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT > 5 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT > 8 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT > 10 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT > 20 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | AST > 3 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | AST > 5 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | AST > 8 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | AST > 10 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | AST > 20 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT or AST > 3 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT or AST > 5 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT or AST > 8 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT or AST > 10 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT or AST > 20 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | TBL > 1.5 × ULN | 1 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | TBL > 2 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | TBL > 3 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALP > 2 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALP > 3 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALP > 5 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT or AST > 3 × ULN & TBL > 2 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT or AST > 5 × ULN & TBL > 2 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT or AST > 8 × ULN & TBL > 2 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT or AST > 10 × ULN & TBL > 2 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALP > 3 × ULN & TBL > 2 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALP > 5 × ULN & TBL > 2 × ULN | 0 participants |
| Secukinumab 150mg | Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities | ALT or AST> 3 × ULN & TBL> 2 × ULN & ALP <2 × ULN | 0 participants |
Secondary
Proportion of Participants Achieving ASAS Partial Remission
The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients achieving an ASAS partial remission The ASAS partial remission criteria are defined as a value not above 2 units in each of the four main domains on a scale of 10
Time frame: week 16
Population: FAS
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Secukinumab 150mg | Proportion of Participants Achieving ASAS Partial Remission | 6 participants | 20 |