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Ankylosing SpondylitisPhase 4ASLeapNCT03350815

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

A Phase 4 study testing 150 mg open-label secukinumab, 150 mg double-blinded secukinumab and 300 mg double-blinded secukinumab in people with Ankylosing Spondylitis, run by Novartis Pharmaceuticals at 65 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This was a study estimating the clinical difference between 300 mg and 150 mg of secukinumab following dose escalation to 300 mg in patients with ankylosing spondylitis Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ankylosing Spondylitis
What is being tested?
150 mg open-label secukinumab, 150 mg double-blinded secukinumab and 300 mg double-blinded secukinumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
322 participants
Where
65 sitesUnited States
Study dates
13 Mar 2018to 29 May 2021
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Understand and communicate with the investigator, comply with the requirements of the study and give a written, signed and dated informed consent
  • Male or non-pregnant, non-lactating female patients at least 18 years of age
  • Diagnosis of moderate to severe Ankylosing Spondylitis (AS) with prior documented radiologic evidence fulfilling the Modified New York criteria for AS
  • Active AS assessed by total Bath Ankylosing Spondylitis Disease Activity index (BASDAI) ≥ 4 (0-10) at baseline
  • Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at baseline
  • Total back pain as measured by visual analog scale (VAS) ≥ 40 mm (0-100 mm) at baseline
Show all 9Show fewer
  • 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
  • Stable dose of NSAIDs including Cyclooxygenase-1 (COX-1) or Cyclooxygenase-2 (COX-2) inhibitors for at least 2 weeks before their Baseline Visit
  • 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

Who cannot join

  • Total ankylosis of the spine
  • Use of other investigational drugs within 5 half-lives of enrollment, or within 4 weeks before the Baseline Visit, whichever is longer.
  • History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.
  • 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.
  • 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
  • Patients who have taken more than one anti-TNFα agent
Show all 11Show fewer
  • Any intramuscular or intravenous corticosteroid injection within 2 weeks before baseline
  • Any therapy by intra-articular injections (e.g. corticosteroid) within 4 weeks before baseline
  • Previous treatment with any cell-depleting therapies
  • Patients taking high potency opioid analgesics (e.g., methadone, hydromorphone, morphine)
  • Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

65 sites in 1 country.

65 sites in 1 country

United States65 sites

  • Novartis Investigative Site

    Albuquerque, New Mexico, 87102

  • Novartis Investigative Site

    Ann Arbor, Michigan, 48109 5271

  • Novartis Investigative Site

    Aventura, Florida, 33180

  • Novartis Investigative Site

    Beaumont, Texas, 77701

  • Novartis Investigative Site

    Boca Raton, Florida, 33486

  • Novartis Investigative Site

    Boston, Massachusetts, 02111

  • Novartis Investigative Site

    Brandon, Florida, 33511

  • Novartis Investigative Site

    Brooklyn, New York, 11201

  • Novartis Investigative Site

    Charleston, South Carolina, 29460

  • Novartis Investigative Site

    Charleston, West Virginia, 25304

  • Novartis Investigative Site

    Cincinnati, Ohio, 45219

  • Novartis Investigative Site

    Colleyville, Texas, 76034

  • Novartis Investigative Site

    Columbia, South Carolina, 29204

  • Novartis Investigative Site

    Corvallis, Oregon, 97330

  • Novartis Investigative Site

    Cumberland, Maryland, 21740

  • Novartis Investigative Site

    Dallas, Texas, 75231

  • Novartis Investigative Site

    Dayton, Ohio, 45402

  • Novartis Investigative Site

    DeLand, Florida, 32720

  • Novartis Investigative Site

    Duluth, Georgia, 30096

  • Novartis Investigative Site

    Duncansville, Pennsylvania, 16635

  • Novartis Investigative Site

    Edina, Minnesota, 55435

  • Novartis Investigative Site

    Evansville, Indiana, 47715

  • Novartis Investigative Site

    Fullerton, California, 92835

  • Novartis Investigative Site

    Gainesville, Florida, 32608

  • Novartis Investigative Site

    Hagerstown, Maryland, 21740

  • Novartis Investigative Site

    Houston, Texas, 77025

  • Novartis Investigative Site

    Houston, Texas, 77089

  • Novartis Investigative Site

    Jackson, Tennessee, 38305

  • Novartis Investigative Site

    Jonesboro, Arkansas, 72401

  • Novartis Investigative Site

    Loma Linda, California, 92354

  • Novartis Investigative Site

    Manitowoc, Wisconsin, 54220

  • Novartis Investigative Site

    Memphis, Tennessee, 38119

  • Novartis Investigative Site

    Mesquite, Texas, 75150

  • Novartis Investigative Site

    Middleburg Heights, Ohio, 44130

  • Novartis Investigative Site

    Midland Park, New Jersey, 07432

  • Novartis Investigative Site

    Minot, North Dakota, 58701

  • Novartis Investigative Site

    Monroe, Louisiana, 71203

  • Novartis Investigative Site

    New York, New York, 10016

  • Novartis Investigative Site

    Oklahoma City, Oklahoma, 73103

  • Novartis Investigative Site

    Onalaska, Wisconsin, 54650

  • Novartis Investigative Site

    Orchard Park, New York, 14127

  • Novartis Investigative Site

    Orlando, Florida, 32810

  • Novartis Investigative Site

    Palm Desert, California, 92260

  • Novartis Investigative Site

    Plantation, Florida, 33324

  • Novartis Investigative Site

    Portland, Oregon, 97239

  • Novartis Investigative Site

    Potsdam, New York, 13676

  • Novartis Investigative Site

    Saint Clair Shores, Michigan, 48081

  • Novartis Investigative Site

    Salt Lake City, Utah, 84132

  • Novartis Investigative Site

    Santa Fe, New Mexico, 87505

  • Novartis Investigative Site

    Seattle, Washington, 98104

  • Novartis Investigative Site

    Seattle, Washington, 98195

  • Novartis Investigative Site

    Spokane, Washington, 99204

  • Novartis Investigative Site

    Springfield, Illinois, 62703

  • Novartis Investigative Site

    Springfield, Missouri, 65810

  • Novartis Investigative Site

    St. Petersburg, Florida, 33705

  • Novartis Investigative Site

    Tamarac, Florida, 33321

  • Novartis Investigative Site

    Tampa, Florida, 33609

  • Novartis Investigative Site

    Tustin, California, 92780

  • Novartis Investigative Site

    Upland, California, 91786

  • Novartis Investigative Site

    Vernon Hills, Illinois, 60061

  • Novartis Investigative Site

    Voorhees Township, New Jersey, 08043

  • Novartis Investigative Site

    Wexford, Pennsylvania, 15090

  • Novartis Investigative Site

    Wheaton, Maryland, 20902

  • Novartis Investigative Site

    Worcester, Massachusetts, 01655

  • Novartis Investigative Site

    Zephyrhills, Florida, 33542

Other trials in United States

About this study

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)

This was a study estimating the clinical difference between 300 mg and 150 mg of secukinumab following dose escalation to 300 mg in patients with ankylosing spondylitis

Read the detailed description

The study used a multicenter design which included an initial 16 week open-label period (Treatment Period 1) followed by a randomized, double-blind, parallel-group period (Treatment Period 2),

  1. Screening: A Screening Period took place over 2 separate visits, with the first visit used to assess eligibility and to washout prohibited medications (up to 11 weeks). The second Screening Visit, which occurred at a minimum of 2 weeks prior to the Baseline Visit for all patients, was used to further assess eligibility and to initiate patients on the sensor actigraphy device and morning sleep questionnaires which collected data over the 2-week Screening Period to establish Baseline data. Note: Patients who did not require a washout, and who satisfied all inclusion and none of the exclusion criteria at the first Screening Visit, could initiate the second Screening Visit 1 (SV1) week after their first Screening Visit.
  2. Treatment Period 1: Patients who met all of the inclusion criteria and none of the exclusion criteria had a Baseline Visit performed to start Treatment Period 1. During this 16-week period, all patients received open-label secukinumab 150 mg (1 x 1.0mL subcutaneously [s.c.]) at Baseline, Weeks 1, 2, 3, 4, 8, and 12.

At Week 16, patients were placed into 1 of the following groups:

  1. Responders (Rs): Patients who achieved ASDAS inactive disease (total score < 1.3) at both Week 12 and Week 16 and who achieved a decrease (improvement) from Baseline in total ASDAS score at both Week 12 and Week 16.
  2. Inadequate responders (IRs): Patients who had active disease, defined as an ASDAS total score of ≥ 1.3 at either Week 12 or Week 16, and who achieved a decrease (improvement) from Baseline in total ASDAS score at both Week 12 and Week 16.
  3. Nonresponders: Patients who exhibited no change or an increase (worsening) from Baseline in total ASDAS score at either Week 12 or Week 16.

Note: To minimize patient burden, at the Week 16 Visit, the hs-CRP measurement that is part of the ASDAS calculation was imputed from the Week 12 hs-CRP results to allow for assignment into the groups above. Historically, hs-CRP levels have varied little between Week 12 and Week 16 or in previous studies of secukinumab in active AS.

  1. Treatment Period 2: Upon completion of the Week 16 visit,
  2. Responders entered Treatment Period 2 and continued to receive secukinumab 150 mg every 4 weeks through Week 48 as well as 1 matched placebo dose (s.c. injection) to maintain the integrity of the blind for the randomized IR group.
  3. Inadequate responders entered Treatment Period 2 and were randomized (1:1, double blinded) to secukinumab 300 mg or secukinumab 150 mg every 4 weeks through Week 48. Patients knew that they were on secukinumab, but were blinded to dose, so they did not know whether they were receiving 150 mg or 300 mg.
  4. Nonresponders were discontinued from the study at Week 16. The only condition that was placed on enrollment targets was that no less than 60% of patients (162 patients) were tumor necrosis factor alpha (TNFα) inhibitor naive (or, no more than 40% of patients were TNF-IR). In theory the percentage of TNFα inhibitor naive patients could have reached 100%, although that was not anticipated.

Patients could discontinue the study at any time. If rescue treatment with prohibited medications (as described in Section 9.4.7) occurred, patients were discontinued from the study and were to return for an End of Study Visit. The End of Study Visit was scheduled approximately 4 weeks after the last study treatment and was performed before any new treatment was initiated. After the End of Study Visit, any serious adverse events (SAEs) that occurred in the following 30 days were required to be reported.

Being tested
150 mg open-label secukinumab, 150 mg double-blinded secukinumab, 300 mg double-blinded secukinumab
Keywords
Ankylosing spondylitis, ASDAS inactive disease, secukinumab, ASDAS
Medical subject headings
Spondylitis, Ankylosing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 150 mg open-label secukinumabDrug

    Also called AIN457

    All patients in Treatment Period 1 received 150 mg s.c. injection open-label secukinumab.

  • 150 mg double-blinded secukinumabDrug

    Also called AIN457

    Treatment Period 2 Patients who achieved responder status entered Treatment Period 2 and continued to receive 150 mg s.c. (1 s.c. injection of secukinumab 150 mg)

  • 300 mg double-blinded secukinumabDrug

    Also called AIN457

    Treatment Period 2 300 mg (2 s.c. injections of the 150 mg dose)

Study groups in NCT03350815
Study groupRoleWhat they receive
RespondersActive comparatorPatients who achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (total score <1.3) at both Week 12 and Week 16.
Receives: Drug: 150 mg open-label secukinumab; Drug: 150 mg double-blinded secukinumab
Inadequate respondersActive comparatorPatients 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 achieved a decrease (improvement) from baseline in total ASDAS score at both Week 12 and Week 16.
Receives: Drug: 150 mg open-label secukinumab; Drug: 150 mg double-blinded secukinumab; Drug: 300 mg double-blinded secukinumab
Non-respondersActive comparatorPatients 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 were not entered Treatment Period 2. Non-responders were discontinued from the study at Week 16.
Receives: Drug: 150 mg open-label secukinumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Proportion of Participants Who Achieved Inactive Disease Based on the Ankylosing Spondylitis Disease Activity Score (ASDAS) Measure

    Proportion of participants with inadequate response at week 16 who achieved inactive disease at Week 52 The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite index to assess disease activity in AS. The ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) were utilized to assess the disease activity status.

    • < 1.3 between inactive disease and moderate disease activity,
    • < 2.1 between moderate disease activity and high disease activity, and
    • 3.5 between high disease activity and very high disease activity.

    Measured: Week 52

Secondary outcomes (8)

  1. The Proportion of Participants Who Achieved a Clinically Important Improvement on the Ankylosing Spondylitis Disease Activity Score (ASDAS) Scale

    A reduction from baseline in ASDAS score of ≥1.1 was 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.

    The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite index to assess disease activity in AS. The ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) wias utilized to assess the disease activity status.

    • < 1.3 between inactive disease and moderate disease activity,
    • < 2.1 between moderate disease activity and high disease activity, and
    • 3.5 between high disease activity and very high disease activity.

    Measured: Baseline, Week 52

  2. Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

    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.

    Measured: Baseline, Week 52

  3. Proportion of Patients Who Achieved Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI-50)

    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.

    Measured: Baseline, Week 52

  4. The Proportion of Participants Who Achieved an ASAS 20 Response (Assessment of SpondyloArthritis International Society Criteria)

    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.

    An ASAS20 response is defined as an improvement of ≥20% from baseline and absolute improvement from baseline of at least 1 on a 0-to-10 scale in at least 3 of the following 4 domains: patient global, total back pain, function (BASFI), and inflammation (average of the last 2 questions of the BASDAI concerning morning stiffness). An absence of deterioration from baseline (deterioration defines as ≥20% worsening and absolute worsening of at last 1 on a 0-to-10 scale) in the potential remaining domain.

    Measured: Week 52

  5. The Proportion of Participants Who Achieved an ASAS 40 Response

    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.

    An ASAS40 response is defined as a ≥40% improvement in 3 of the 4 domains with an absolute improvement of at least 2 on a 0-to-10 scale, and no worsening in the remaining domain.

    Measured: Week 52

  6. The Proportion of Patients Who Achieved 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 0-10. In this study, ASAS partial remission is used to estimate the difference in response between 150mg and 300mg of secukinumab.

    Measured: Week 52

  7. Change in ASAS - Health Index Over Time

    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. Lower score indicating a better health status

    Measured: Baseline, Week 52

  8. Change in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Over Time

    Fatigue was assessed using the 13-item FACIT-fatigue scale for the assessment of fatigue in cancer patients.24 The FACIT-Fatigue is a validated questionnaire that was originally developed for the precise evaluation of fatigue levels in cancer patients with anemia. It consists of 13 questions using a 5 point scale (0=not at all; 1 = a little bit, 2 = somewhat, 3 = quite a bit and 4 = very much). Responses to each question were added with equal weight to obtain a total score. The range of possible scores is 0-52, with 0 corresponding to the highest level of fatigue and 52 corresponding to the lowest level of fatigue.

    Measured: Baseline, Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Nov 2017
  2. Study start13 Mar 2018
  3. Primary completion11 Mar 2021
  4. Study completion29 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This was a randomized, double-blind, parallel-group, multicenter design which included an initial 16 week open-label period (Treatment Period 1) followed by a randomized, double-blind, parallel-group period (Treatment Period 2),
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
322 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03350815
Sponsor's protocol ID
CAIN457FUS06
Acronym
ASLeap
Status last verified
Apr 2022
First submitted
31 Oct 2017
Last updated
29 Apr 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • Deodhar A, Kivitz AJ, Magrey M, Walsh JA, Mease PJ, Greenwald M, Kianifard F, Elam C, Bommidi GM, Winseck A, Gensler LS. A secukinumab dose-escalation study in patients with ankylosing spondylitis not achieving inactive disease after 16 weeks of treatment. Rheumatology (Oxford). 2025 Apr 1;64(4):1864-1872. doi: 10.1093/rheumatology/keae432.

    PubMed 39133200

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing 150 mg open-label secukinumab, 150 mg double-blinded secukinumab and 300 mg double-blinded secukinumab in people with Ankylosing Spondylitis, run by Novartis Pharmaceuticals at 65 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 65 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Proportion of Participants Who Achieved Inactive Disease Based on the Ankylosing Spondylitis Disease Activity Score (ASDAS) Measure (time frame: Week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03350815, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2022.

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ASLeap Clinical Trial NCT03350815 | AzTrials