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Study Estimating the Clinical Difference Between 300 mg and 150 mg of Secukinumab Following Dose Escalation to 300 mg in Patients With Ankylosing Spondylitis (ASLeap)

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ClinicalTrials.gov Identifier: NCT03350815
Recruitment Status : Active, not recruiting
First Posted : November 22, 2017
Last Update Posted : October 1, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE October 31, 2017
First Posted Date  ICMJE November 22, 2017
Last Update Posted Date October 1, 2020
Actual Study Start Date  ICMJE March 13, 2018
Estimated Primary Completion Date May 28, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2017)
The proportion of participants who achieve inactive disease based on the Ankylosing Spondylitis Disease Activity Score (ASDAS) measure [ Time Frame: Week 52 ]
An ASDAS inactive disease response is a score of <1.3 on a composite index to assess disease activity in Ankylosing Spondylitis. Parameters include spinal pain, the patient's global assessment of disease activity, peripheral pain/swelling, duration of morning stiffness and C-reactive protein (CRP) in mg/L. In this study, ASDAS is used to estimate the difference in response between 150mg and 300mg of secukinumab.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2017)
  • The proportion of participants who achieve a clinically important improvement on the Ankylosing Spondylitis Disease Activity Score (ASDAS) scale [ Time Frame: Week 52 ]
    A change from baseline in ASDAS score of ≥1.1 is considered a clinically important improvement in disease activity in Ankylosing Spondylitis. In this study, ASDAS is used to estimate the difference in response between 150mg and 300mg of secukinumab.
  • Change over time in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [ Time Frame: Week 52 ]
    BASDAI is a validated assessment tool using 0 through 10 scales (0 indicating "no problem" and 10 indicating "worst problem"), to characterize six clinical domains pertaining to five major symptoms of AS perceived by the patients. Computed composite scores of 4 or greater indicate suboptimal disease control. In this study, BASDAI is used to estimate the difference in response between 150mg and 300mg of secukinumab.
  • Proportion of patients who achieve Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI-50) [ Time Frame: Week 52 ]
    BASDAI-50 represents a change from baseline (improvement) of at least 50% in BASDAI score. In this study, BASDAI is used to estimate the difference in response between 150mg and 300mg of secukinumab.
  • The proportion of participants who achieve an ASAS 20 response (Assessment of SpondyloArthritis International Society criteria) [ Time Frame: Week 52 ]
    ASAS 20 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame at least 20% improvement in score in at least 3 of a conventional set of 4 clinical domains relevant to AS and no worsening in the fourth domain. In this study, ASAS20 is used to estimate the difference in response between 150mg and 300mg of secukinumab.
  • The proportion of participants who achieve an ASAS 40 response [ Time Frame: Week 52 ]
    ASAS 40 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame at least 40% improvement in score in at least 3 of a conventional set of 4 clinical domains relevant to AS and no worsening in the fourth domain. In this study, ASAS40 is used to estimate the difference in response between 150mg and 300mg of secukinumab.
  • The proportion of patients who achieve an ASAS partial remission [ Time Frame: Week 52 ]
    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. In this study, ASAS partial remission is used to estimate the difference in response between 150mg and 300mg of secukinumab.
  • Change in ASAS - Health Index over time [ Time Frame: Week 52 ]
    The ASAS-HI is a self-administered questionnaire and measures functioning and health over 17 aspects of health and 9 environmental factors in patients with spondyloarthritis. Patients score each item as "I agree" and "I do not agree". In this study, ASAS-HI is used to estimate the difference in response between 150mg and 300mg of secukinumab.
  • Change in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue over time [ Time Frame: Week 52 ]
    The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. It is administered at Visits 4 - 19. ". In this study, FACIT-Fatigue is used to estimate the difference in response between 150mg and 300mg of secukinumab.
  • Number of participants with treatment-related adverse events or serious adverse events [ Time Frame: Week 52 ]
    These assessments will be implemented in terms of physical examination and vital signs outcomes, clinical laboratory results, nature and frequency of the observed adverse events and serious adverse events, frequency and severity of any injection site reactions, ECG outcomes and the detection of immunogenicity.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Estimating the Clinical Difference Between 300 mg and 150 mg of Secukinumab Following Dose Escalation to 300 mg in Patients With Ankylosing Spondylitis
Official Title  ICMJE A Randomized, Double-blind, Parallel-group, Multicenter Study of Secukinumab to Compare 300 mg and 150 mg at Week 52 in Patients With Ankylosing Spondylitis Who Are Randomized to Dose Escalation After Not Achieving Inactive Disease During an Initial 16 Weeks of Open-label Treatment With Secukinumab 150 mg (ASLeap)
Brief Summary Study estimating the clinical difference between 300 mg and 150 mg of secukinumab following dose escalation to 300 mg in patients with ankylosing spondylitis
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:
Patients and Investigators will be blinded to the secukinumab dose during Treatment Period 2.
Primary Purpose: Treatment
Condition  ICMJE Ankylosing Spondylitis
Intervention  ICMJE
  • Drug: 150 mg open-label secukinumab
    All patients in Treatment Period 1 will receive 150 mg open-label secukinumab.
    Other Name: AIN457
  • Drug: 150 mg double-blinded secukinumab
    Treatment Period 2
    Other Name: AIN457
  • Drug: 300 mg double-blinded secukinumab
    Treatment Period 2
    Other Name: AIN457
Study Arms  ICMJE
  • Active Comparator: Responders
    Patients achieving an Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (total score <1.3) at both Week 12 and Week 16.
    Interventions:
    • Drug: 150 mg open-label secukinumab
    • Drug: 150 mg double-blinded secukinumab
  • Active Comparator: Inadequate responders
    Patients who have active disease, defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) total score of >1.3 at both Week 12 and Week 16, and who do achieve a decrease (improvement) from baseline in total ASDAS score at both Week 12 and Week 16.
    Interventions:
    • Drug: 150 mg open-label secukinumab
    • Drug: 150 mg double-blinded secukinumab
    • Drug: 300 mg double-blinded secukinumab
  • Active Comparator: Non-responders

    Patients who exhibit no change or an increase (worsening) from baseline in total Ankylosing Spondylitis Disease Activity Score (ASDAS) score at either Week 12 or Week 16.

    Non-responders will not enter Treatment Period 2. Non-responders will be discontinued from the study at Week 16.

    Intervention: Drug: 150 mg open-label secukinumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 22, 2020)
313
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2017)
270
Estimated Study Completion Date  ICMJE May 28, 2021
Estimated Primary Completion Date May 28, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Understand and communicate with the investigator, comply with the requirements of the study and give a written, signed and dated informed consent
  2. Male or non-pregnant, non-lactating female patients at least 18 years of age
  3. Diagnosis of moderate to severe Ankylosing Spondylitis (AS) with prior documented radiologic evidence fulfilling the Modified New York criteria for AS
  4. Active AS assessed by total Bath Ankylosing Spondylitis Disease Activity index (BASDAI) ≥ 4 (0-10) at baseline
  5. Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at baseline
  6. Total back pain as measured by visual analog scale (VAS) ≥ 40 mm (0-100 mm) at baseline
  7. Patients should have been on non-steroidal anti-inflammatory drugs (NSAIDs) at the maximum tolerated dose for at least 4 weeks prior to their Baseline Visit, with an inadequate response or for less than 4 weeks if withdrawn for intolerance, toxicity or contraindications
  8. Stable dose of NSAIDs including Cyclooxygenase-1 (COX-1) or Cyclooxygenase-2 (COX-2) inhibitors for at least 2 weeks before their Baseline Visit
  9. Patients who have been on a tumor necrosis factor alpha (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 had been intolerant upon administration of an anti-TNFα agent

Key Exclusion Criteria:

  1. Total ankylosis of the spine
  2. Use of other investigational drugs within 5 half-lives of enrollment, or within 4 weeks before the Baseline Visit, whichever is longer.
  3. History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.
  4. Chest x-ray, computerized tomography (CT) scan, or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician.
  5. Previous exposure to secukinumab or any other biologic drug directly targeting Interleukin-17 (IL-17), Interleukin-12/23 (IL-12/23), or the IL-17 receptor, or any other biologic immunomodulating agent, except those targeting TNFα
  6. Patients who have taken more than one anti-TNFα agent
  7. Any intramuscular or intravenous corticosteroid injection within 2 weeks before baseline
  8. Any therapy by intra-articular injections (e.g. corticosteroid) within 4 weeks before baseline
  9. Previous treatment with any cell-depleting therapies
  10. Patients taking high potency opioid analgesics (e.g., methadone, hydromorphone, morphine)

Other protocol-defined inclusion/exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03350815
Other Study ID Numbers  ICMJE CAIN457FUS06
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect 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

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP