16-week Efficacy and 2-year Safety, Tolerability and Efficacy of Secukinumab in Participants With Active Ankylosing Spondylitis

Phase 3

Completed

Conditions: Spondylitis, Ankylosing

Interventions: Biological: Secukinumab
Biological: Placebo

Registration Number: NCT02159053

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The purpose of this study is to provide 16-week efficacy, safety and tolerability data versus placebo to support the use of secukinumab 150 mg by subcutaneous (s.c.) self-administration with or without a loading regimen and maintenance dosing using pre-filled syringe (PFS) and to assess efficacy, safety and tolerability up to 2 years in subjects with active AS despite current or previous NSAID, non-biologic DMARD, or biologic anti-TNFα therapy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 350

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Secukinumab 150 mg s.c. without loading	Secukinumab	Secukinumab 150 mg at Baseline, followed by dosing every four weeks starting at Week 4, with Placebo at Weeks 1, 2, and 3.
Placebo	Placebo	Placebo at Baseline, Weeks 1, 2, 3, 4, 8, and 12, followed by dosing with Secukinumab 150 mg every four weeks starting at Week 16.
Secukinumab 150 mg s.c. with loading	Secukinumab	Secukinumab 150 mg at Baseline, Weeks 1, 2, and 3, followed by dosing every four weeks starting at Week 4.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Responded for Assessment of Spondyloarthritis International Society 20 Criteria (ASAS20) at 16 Weeks	16 Weeks	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 20 percent (%) and 1 unit on a scale of 10 in three main domains and no worsening of at least 20% and 1 unit on a scale of 10 in the fourth domain within a defined time frame. Four main ASAS domains include: 1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe 2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale 4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem)

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Responded for ASAS 5/6 Response at 16 Weeks	16 Weeks	ASAS 5/6 response is a validated composite assessment, defined as an improvement of at least 20% in score in at least 5 of 6 clinical domains relevant to ankylosing spondylitis and no worsening in the remaining domain. ASAS domains includes: 1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe 2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain 3. Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale 4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem) 5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment 6. C-reactive protein (CRP, acute phase reactant).
Change From Baseline in Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) at 16 Weeks	Baseline, 16 Weeks	ASQoL is a self-administered 18 item questionnaire that assesses disease-specific quality of life (QoL), consisting of statements that are relevant to the physical and mental conditions for a subject with ankylosing spondylitis: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score ranges from 0 (good QoL) to 18 (poor QoL). The change in ASQoL scores was evaluated using a mixed effect repeated measures model (MMRM).
Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at 16 Weeks	Baseline, 16 Weeks	Blood levels of C-reactive protein (CRP) is an acute phase reactant, which are indicative of inflammation and of its severity, and can be used to monitor treatment response. A hsCRP test is implemented to assess the efficacy of secukinumab (with or without load) versus placebo in reducing ankylosing spondylitis elicited systemic inflammation over the time.
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at 16 Weeks	Baseline, 16 Weeks	BASDAI is a validated assessment tool using 0 through 10 scales (0 indicating "no problem" and 10 indicating "worst problem" on continuous VAS), to answer 6 questions (clinical domains) pertaining to 5 major symptoms of ankylosing spondylitis. Computed composite scores of 4 or greater indicate suboptimal disease control. BASDAI questions includes: 1. Fatigue 2. Spinal pain 3. Joint pain / swelling 4. Areas of localized tenderness (called enthesitis, or inflammation of tendons and ligaments) 5. Morning stiffness duration 6. Morning stiffness severity. Each symptom has equal weighting, the mean of two scores related to morning stiffness was taken (questions 5 and 6). The resulting 0 to 10 score was added to the scores from questions 1-4. The resulting 0 to 50 score was divided by 5 to give a final 0-10 BASDAI score. BASDAI was a quick and simple index taking between 30 seconds and 2 minutes for completion.
Number of Participants With Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs) and Related Discontinuations at 104 Weeks	104 Weeks	AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
Percentage of Participants Responded for ASAS 40 Response at Week 4	Week 4	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 40% and 2 unit on a scale of 10 in three main domains and no worsening at all in the remaining domain within a defined time frame. Four main ASAS domains include: 1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe 2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale 4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).
Percentage of Participants Responded for ASAS 40 Response at 16 Weeks	16 Weeks	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 40% and 2 unit on a scale of 10 in three main domains and no worsening at all in the remaining domain within a defined time frame. Four main ASAS domains include: 1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe 2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale 4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).
Change From Baseline in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36)	Baseline, 16 Weeks	SF-36 is a 36 item questionnaire which measures Quality of Life across eight subscales that were scored individually: physical functioning, role- physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores are weighted sums of the questions in each section. Scores range from 0-100. Lower scores = more disability, higher scores = less disability. The overall summary scores, SF-36 physical Component Summary (PCS) was used to assess improvement from baseline in the Health-Related Quality Of Life of subjects. The change in SF-36 scores were evaluated using MMRM.
Percentage of Participants Responded for ASAS 20 at Week 4	Week 4	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 20% and 1 unit on a scale of 10 in three main domains and no worsening of at least 20% and 1 unit on a scale of 10 in the fourth domain within a defined time frame. Four main ASAS domains include: 1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe 2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale 4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).