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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02750592
Recruitment Status : Completed
First Posted : April 25, 2016
Results First Posted : September 9, 2019
Last Update Posted : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Ankylosing Spondylitis Drug: Secukinumab 150 mg provided in 1.0 mL pre-filled syringes (PFSs) for sc injection. Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 22, 2016
Actual Primary Completion Date : July 5, 2017
Actual Study Completion Date : May 16, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Secukinumab

Arm Intervention/treatment
Experimental: secukinumab 150mg
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.
Baseline, 1, 2, 3, 4 week. After 4 week, administered every 4 weeks.




Primary Outcome Measures :
  1. Assessment of SpondyloArthritis International Society 20 Response (ASAS20) [ Time Frame: 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 Outcome Measures :
  1. ASAS 40 Response Rate With Non-responder Imputation (NRI) [ Time Frame: 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


  2. Bath Ankylosing Spondylitis Disease Activity (BASDAI) 50 Response Rate [ Time Frame: 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


  3. Change in High Sensitivity C-Reactive Protein (hsCRP) [ Time Frame: 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


  4. Number of Participants With ASAS 5/6 Response Criteria [ Time Frame: 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


  5. Mean Change From Baseline in BASDAI From Baseline [ Time Frame: 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.


  6. Change From Baseline in Short Form Health Survey Physical Component Summary (SF-36 PCS) Score [ Time Frame: 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.


  7. Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score [ Time Frame: 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)


  8. Proportion of Participants Achieving ASAS Partial Remission [ Time Frame: 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


  9. Change in Serum Concentration of Secukinumab [ Time Frame: 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.


  10. Number of Participants With Immunogenicity Against Secukinumab [ Time Frame: 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.


  11. Number of Participants With Newly Occurring or Worsening Hematology Abnormalities Based on CTCAE Grade, Blood [ Time Frame: 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.


  12. Number of Participants With Newly Occurring or Worsening Chemistry Abnormalities Based on CTCAE Grade [ Time Frame: 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.


  13. Participants With Newly Occurring or Worsening Liver Enzyme Abnormalities [ Time Frame: 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


  14. Number of Participants With Newly Occurring or Worsening Lipid Parameters Abnormalities [ Time Frame: 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

  15. Participants With Newly Occurring Notable Abnormalities in Vital Signs [ Time Frame: 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)




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02750592


Locations
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Japan
Novartis Investigative Site
Kitakyushu-city, Fukuoka, Japan, 807-8556
Novartis Investigative Site
Kita-gun, Kagawa, Japan, 761-0793
Novartis Investigative Site
Nankoku city, Kochi, Japan, 783 8505
Novartis Investigative Site
Tenri, Nara, Japan, 632-8552
Novartis Investigative Site
Okayama-city, Okayama, Japan, 700-0013
Novartis Investigative Site
Kawachinagano, Osaka, Japan, 586-8521
Novartis Investigative Site
Suita city, Osaka, Japan, 565 0871
Novartis Investigative Site
Bunkyo ku, Tokyo, Japan, 113-8431
Novartis Investigative Site
Chuo ku, Tokyo, Japan, 104-8560
Novartis Investigative Site
Shinjuku-ku, Tokyo, Japan, 160-0054
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] November 26, 2015
Statistical Analysis Plan  [PDF] February 6, 2018

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02750592    
Other Study ID Numbers: CAIN457H1301
First Posted: April 25, 2016    Key Record Dates
Results First Posted: September 9, 2019
Last Update Posted: September 9, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Ankylosing Spondylitis
secukinumab
AIN457H
SpondyloArthritis
Additional relevant MeSH terms:
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Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis