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)

• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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

Condition or disease	Intervention/treatment	Phase
Ankylosing Spondylitis	Drug: 150 mg open-label secukinumab; Drug: 150 mg double-blinded secukinumab; Drug: 300 mg double-blinded secukinumab	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 270 participants
• 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
• Official Title: 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)
• Actual Study Start Date: March 13, 2018
• Estimated Primary Completion Date: November 27, 2020
• Estimated Study Completion Date: November 27, 2020

Arms and Interventions

Arm	Intervention/treatment
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.	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
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.	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
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.	Drug: 150 mg open-label secukinumab; All patients in Treatment Period 1 will receive 150 mg open-label secukinumab.; Other Name: AIN457

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.

9. 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals

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Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03350815 History of Changes
• Other Study ID Numbers: CAIN457FUS06
• First Posted: November 22, 2017
• Last Update Posted: July 18, 2019
• Last Verified: July 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Ankylosing spondylitis, ASDAS inactive disease, secukinumab

Additional relevant MeSH terms:

Spondylitis; Spondylitis, Ankylosing; Bone Diseases, Infectious; Infection; Bone Diseases; Musculoskeletal Diseases; Spinal Diseases; Spondylarthropathies; Spondylarthritis; Ankylosis; Joint Diseases; Arthritis; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs