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Trial record 24 of 39 for:    "Spinal Disease" | "Benzocaine"

AScalate: Treat-to-target in Axial Spondyloarthritis (AScalate)

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ClinicalTrials.gov Identifier: NCT03906136
Recruitment Status : Recruiting
First Posted : April 8, 2019
Last Update Posted : August 7, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is a randomized, parallel-group, open-label, multicenter study of patients with active axSpA. The aim is to demonstrate that the efficacy of a Treat-to-Target (T2T) approach (with secukinumab as first-line biologic) is superior to a Standard-Of-Care (SOC) approach in terms of achieving strong clinical efficacy in patients with active axial Spondyloarthritis (axSpA) who are naïve to biological therapy and who have had an inadequate response to non-steroidal anti-inflammatory drugs. The study will include an 8-week Screening period, a 36-week treatment period according to previous randomization, and a safety follow-up period of 20 weeks. The primary endpoint is the percentage of patients achieving an Assessment in SpondyloArthritis international Society response 40 (ASAS40) at Week 24.

Condition or disease Intervention/treatment Phase
Axial Spondyloarthritis Biological: Secukinumab/Adalimumab-Biosimilar Other: Standard-of-care Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open Label Multicenter Trial to Investigate the Efficacy of a Treat-to-target (T2T) Treatment Strategy With Secukinumab (AIN457) as a First-line Biologic Compared to a Standard-of-care (SOC) Treatment Over 36 Weeks in Patients With Active Axial Spondyloarthritis (axSpA)
Actual Study Start Date : June 4, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : June 22, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TREAT-TO-TARGET (T2T)

Participants will receive secukinumab at a dose of 150 milligrams (mg) as subcutaneous (s.c.) injection at 150 mg dose at Baseline, Week 1, 2, 3, 4 and 8. From Week 12, only responders will continue to receive 4-weekly doses until Week 32 if they maintain the response. In case these patients experience a loss of response from week 24 they will be escalated to secukinumab 300 mg s.c. every 4 weeks until Week 32.

Patients who are non-responders at Week 12 will receive 4-weekly secukinumab 300 mg s.c. until Week 24. From Week 24, only responders will continue to receive 4-weekly secukinumab 300 mg s.c. until Week 32. Patients who are non-responders to secukinumab 300 mg at Week 24 will receive biweekly of adalimumab biosimilar 40 mg s.c. until Week 34

Biological: Secukinumab/Adalimumab-Biosimilar
Secukinumab 150 mg, s.c. Secukinumab 300 mg, s.c. Adalimumab-Biosimilar, s.c.

Active Comparator: Standard-of-care (SOC)
SOC treatment up to the maximum recommended dose at the discretion of the investigator as according to current recommendation for treatment of axSpA
Other: Standard-of-care
Patients will receive treatment according to local practice standards by their treating physician following the current treatment recommendations.




Primary Outcome Measures :
  1. Percentage of patients achieving an Assessment of responders for the SpondyloArthritis International Society (ASAS) 40 response [ Time Frame: 24 weeks ]

    The ASAS response measures consist of the following Domains:

    1. Patient's global assessment of disease activity measured on a visual analog scale (VAS).
    2. Patient's assessment of back pain, represented by either total or nocturnal pain scores, both measured on a VAS scale.
    3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by VAS.
    4. Inflammation represented by mean duration and severity of morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) as measured by VAS scale.
    5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment
    6. C-Reactive Protein (CRP)

    ASAS40 response is defined as an improvement of ≥ 40% and ≥ 2 units on a scale of 10 in at least 3 of the 4 domains and no worsening at all in the remaining domain.



Secondary Outcome Measures :
  1. Percentage of patients achieving an ASAS40 response [ Time Frame: Week 12 ]
    ASAS40 response is defined as an improvement of ≥ 40% and ≥ 2 units on a scale of 10 in at least 3 of the 4 domains and no worsening at all in the remaining domain.

  2. Percentage of patients achieving ASAS20, ASAS partial response [ Time Frame: Week 12 and week 24 ]

    ASAS20 response is defined as an improvement of ≥ 20% and ≥ 1 unit on a scale of 0 to 10 in at least 3 of the 4 domains, and no worsening at all in the remaining domain.

    ASAS partial remission is a composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame a value not above 2 units in each of the 4 ASAS domains on a scale of 10.


  3. The proportion of patients meeting the Ankylosing Spondylitis Disease Activity Score (ASDAS) definition of inactive disease, ASDAS clinically important and major improvement and ASDAS low disease activity [ Time Frame: Week 12 and week 24 ]

    Parameters used for the ASDAS include spinal pain (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI question 2), the patient's global assessment of disease activity, peripheral pain/swelling (BASDAI question 3), duration of morning stiffness (BASDAI question 6) and C-reactive Protein or Erythrocyte Sedimentation Rate).

    The 3 values selected to separate disease activity states were < 1.3 between inactive disease and low disease activity, < 2.1 between low disease activity and high disease activity, and > 3.5 between high disease activity and very high disease activity. Selected cutoffs for improvement scores were a change of ≥ 1.1 unit for "minimal clinically important improvement" and a change of ≥ 2.0 units for "major improvement".


  4. The proportion of patients achieving the Bath Ankylosing Spondylitis Disease Activity Index response 50% (BASDAI 50) at Week 12 and Week 24 [ Time Frame: Week 12 and week 24 ]
    The BASDAI consists of a 0 through 10 scale (0 being no problem and 10 being the worst problem, captured as a continuous VAS), which is used to answer 6 questions pertaining to the 5 major symptoms of the disease

  5. The between-treatment difference in change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) [ Time Frame: Week 12 and week 24 ]
    The Bath Ankylosing Spondylitis Functional Index (BASFI) is a set of 10 questions designed to determine the degree of functional limitation in those patients with AS. The 10 questions were chosen with major input from patients with AS. The first 8 questions consider activities related to functional anatomy. The final 2 questions assess the patients' ability to cope with everyday life. A 0 through 10 scale (captured as a continuous VAS) is used to answer the questions. The mean of the 10 scales gives the BASFI score - a value between 0 and 10.

  6. The between-treatment difference in change from Baseline in Bath ankylosing spondylitis metrology index (BASMI) and chest expansion [ Time Frame: Week 12 and week 24 ]

    The BASMI is a validated instrument that uses the minimum number of clinically appropriate measurements that accurately assess axial status, with the goal to define clinically significant changes in spinal movement. Parameters include:

    1. Lateral spinal flexion
    2. Tragus-to-wall distance
    3. Lumbar flexion (modified Schoeber)
    4. Maximal intermalleolar distance
    5. Cervical rotation angle

      Additionally, the following assessments should be taken:

    6. Chest expansion
    7. Occiput-to-wall distance

  7. Change from baseline in the ASQoL (Ankylosing Spondylitis Quality of Life instrument) [ Time Frame: Week 12 and week 24 ]
    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). As such, lower scores indicate better quality of life. Items include an assessment of mobility/energy, self-care and mood/emotion. The recall period is "at the moment," and the questionnaire requires approximately 6 minutes to complete. The purpose of the ASQoL is to assess the disease specific QoL of patients in this study.

  8. The between-treatment difference in change from baseline in ASAS-HI (Ankylosing Spondyloarthritis International Society Health Index) [ Time Frame: Week 12 and week 24 ]
    The ASAS-HI is a disease-specific questionnaire that was developed based on the comprehensive International Classification of Functioning, Disability and Health Core Set (also known as the ICF Core Set) for AS. The ASAS HI is a linear composite measure and contains 17 items (dichotomous response option: "I agree" and "I do not agree"), which cover most of the ICF Core Set. The ASAS HI contains items addressing categories of pain, emotional functions, sleep, sexual function, mobility, self-care, and community life. The total sum of the ASAS HI ranges from 0 to 17, with a lower score indicating a better health status. In addition, the Environmental Factor (EF) Item Set contains items addressing categories of support/relationships, attitudes and health services. The EF Item Set contains 9 dichotomous items with an identical response option but without a sum score because of its multidimensional nature .

  9. The between-treatment difference in change from Baseline in global disease assessment (patient) [ Time Frame: Week 12 and week 24 ]
    • The patient's global assessment of disease activity will be performed using a 100 mm VAS ranging from not severe to very severe, after the question "How active was your disease on average during the last week?"

  10. The between-treatment difference in change from Baseline in global disease assessment (physician) [ Time Frame: Week 12 and week 24 ]
    • The physician's global assessment of disease activity will be performed using 100 mm VAS ranging from no disease activity to maximal disease activity, after the question "Considering all the ways the disease affects your patient, draw a line on the scale for how well his or her condition is today." To enhance objectivity, the physician must not be aware of the specific patient's global assessment of disease activity when performing his own assessment on that patient.

  11. The between-treatment difference in change from Baseline in pain [ Time Frame: Week 12 and week 24 ]
    • The patient's assessment of back pain will be performed using a 100 mm VAS ranging from no pain to unbearable pain, after the question "Based on your assessment, please indicate what is the amount of back pain at any time that you experienced during the last week?" and "Based on your assessment, please indicate what is the amount of back pain at night that you experienced during the last week?".



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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 Axial Spondyloarthritis, axSpA (either Non-Radiographic Axial Spondyloarthritis or Radiographic Axial Spondyloarthritis) fulfilling the Ankylosing Spondyloarthritis International Society classification criteria for axSpA
  • Active disease as defined by having an Ankylosing Spondylitis Disease Activity Score ≥ 2.1 at Screening and Baseline despite concurrent Non-Steroidal Anti-Inflammatory Drug (NSAID) therapy, or intolerance/contraindication to NSAIDs.
  • Objective signs of inflammation at Screening as defined by: Magnetic Resonance Imaging (MRI) of sacroiliac joints performed up to 3 months prior to screening showing acute inflammatory lesion(s), OR elevated quick C-reactive Protein (CRP) (> 5 mg/L), OR MRI showing acute inflammatory lesion(s) in the sacroiliac joints and spine performed during screening period.
  • Inadequate response to NSAIDs

Exclusion Criteria:

  • Previous exposure to secukinumab or other biologic drug directly targeting Interleukin(IL)-17 or IL-17 receptor.
  • Patients who have previously been treated with Tumor Necrosis Factor Alpha inhibitors (investigational or approved).
  • Patients treated with any cell-depleting therapies.
  • Active ongoing inflammatory diseases or underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, which in the opinion of the investigator immunosuppressed the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy.
  • History of clinically significant liver disease or liver injury
  • History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum creatinine level exceeding 1.8 mg/dL (159.12 μmol/L).
  • Active systemic infections during the last 2 weeks (exception: common cold) prior to randomization.
  • History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis (TB) infection
  • Patients positive for human immunodeficiency virus, hepatitis B or hepatitis C
  • Life vaccinations within 6 weeks prior to Baseline or planned vaccination during study participation until 12 weeks after last study treatment administration.

Other protocol-defined inclusion/exclusion criteria may apply.


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): NCT03906136


Contacts
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Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
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Germany
Novartis Investigative Site Recruiting
Berlin, Germany, 12161
Novartis Investigative Site Recruiting
Berlin, Germany, 13353
Novartis Investigative Site Recruiting
Dresden, Germany, 01307
Novartis Investigative Site Recruiting
Ehringshausen, Germany, 35630
Novartis Investigative Site Recruiting
Hamburg, Germany, 20095
Novartis Investigative Site Recruiting
Hamburg, Germany, 22391
Novartis Investigative Site Recruiting
Rendsburg, Germany, 24768
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03906136     History of Changes
Other Study ID Numbers: CAIN457HDE01
First Posted: April 8, 2019    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
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


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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 ):
axial spondyloarthritis (axSpA)
treat-to-target (T2T)
secukinumab
AIN457
Non-Radiographic Axial Spondyloarthritis (nr-axSpA)
Radiographic Axial Spondyloarthritis (r-axSpA)
Additional relevant MeSH terms:
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Spinal Diseases
Spondylarthritis
Spondylitis
Bone Diseases
Musculoskeletal Diseases
Arthritis
Joint Diseases
Adalimumab
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antirheumatic Agents
Immunologic Factors
Physiological Effects of Drugs