Study of Efficacy and Safety of Secukinumab in Japanese Patients With Active Ankylosing Spondylitis

Study Overview
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Brief Summary
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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.

Official Title
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An Open-label, Phase III, Study of Subcutaneous Secukinumab to Assess Efficacy, Safety and Tolerability at up to 52 Weeks in Japanese Patients With Active Ankylosing Spondylitis

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Drug: Secukinumab 150 mg provided in 1.0 mL pre-filled syringes (PFSs) for sc injection.


Participation Criteria
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Eligibility Criteria
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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months prior to baseline with an inadequate response or failure to respond, or less than 3 months if therapy had to be withdrawn due to intolerance, toxicity or contraindications Patients who have been on a TNFα inhibitor (not more than one) must have experienced an inadequate response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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: secukinumab 150mg<br>A screening (SCR) epoch running 4-10 weeks before baseline (BSL) was used to assess eligibility followed by 52 weeks of treatment. The treatment periods consist of Treatment period 1 (BSL to Week 24) and Treatment period 2 (Week 24 to Week 52). After Week 52 follows 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 discontinue prematurely. | Drug: Secukinumab 150 mg provided in 1.0 mL pre-filled syringes (PFSs) for sc injection.<br>* Baseline, 1, 2, 3, 4 week. After 4 week, administered every 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Week 16 | 
| 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 | Week 16 | 
| 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 | baseline, Week 16 | 
| 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 | Week 16 | 
| 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. | Baseline, week 16 | 
| 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. | Baseline, week 16 | 
| 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) | Baseline, week 16 | 
| 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 | week 16 | 
| 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. | Baseline, weeks 4, 16, 24, 52, 60 | 
| 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. | week 60 | 
| 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. | week 60 | 
| 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. | week 60 | 
| 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 | week 60 | 
| 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 | week 60 | 
| 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) | week 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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secukinumab, Ankylosing Spondylitis, AIN457H, SpondyloArthritis