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Study to Examine the Clinical Efficacy and the Nonsteroidal Anti-inflammatory Drug (NSAID)-Sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis (ASTRUM)

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ClinicalTrials.gov Identifier: NCT02763046
Recruitment Status : Completed
First Posted : May 5, 2016
Results First Posted : October 9, 2020
Last Update Posted : October 9, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 3, 2016
First Posted Date  ICMJE May 5, 2016
Results First Submitted Date  ICMJE September 16, 2020
Results First Posted Date  ICMJE October 9, 2020
Last Update Posted Date October 9, 2020
Actual Study Start Date  ICMJE May 31, 2016
Actual Primary Completion Date September 24, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 16, 2020)
Proportion of Patients Who Achieved ASAS20 Response in the Pooled Secukinumab Group Compared With the Placebo Group at Week 12 [ Time Frame: Baseline, Week 12 ]
ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response is defined as an improvement from baseline of ≥20% and ≥1 unit on a scale of 0-10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 0-10 in the remaining domain. The four main ASAS domains are: Patient's global assessment of disease activity, back pain, function represented by ability to perform specific tasks (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]) and inflammation represented by mean duration and severity of morning stiffness. Non-responder imputation was applied for missing data.
Original Primary Outcome Measures  ICMJE
 (submitted: May 3, 2016)
Proportion of patients achieving an ASAS20 response [ Time Frame: Week 12 ]
To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 0 with NSAID tapering allowed from week 4; delayed tapering) at Week 12 is superior to placebo based on the proportion of patients achieving an ASAS20 response.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 16, 2020)
  • Proportion of Patients Who Achieved ASAS20 Response in Each Secukinumab Group (Delayed NSAID Tapering and Early NSAID Tapering) Compared With the Placebo Group [ Time Frame: Baseline, Week 12, Week 16 ]
    ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response is defined as an improvement from baseline of ≥20% and ≥1 unit on a scale of 0-10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 0-10 in the remaining domain. The four main ASAS domains are: Patient's global assessment of disease activity, back pain, function represented by ability to perform specific tasks (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]) and inflammation represented by mean duration and severity of morning stiffness. Non-responder imputation was applied for missing data.
  • Mean Change From Baseline in ASAS-NSAID Score at Week 12 [ Time Frame: Baseline, Week 12 ]
    ASAS-NSAID score is used to present the NSAID (nonsteroidal anti-inflammatory drug) intake by considering the type of NSAID, the total dose and the number of days taking NSAID during a period of interest (PI). For the NSAID equivalence scoring system, "no NSAID intake" was set to a score value of 0, and the reference dose of 150 mg/day diclofenac was set to a score value of 100. The Daily diclofenac-equivalent dose score was derived by converting each daily dose of NSAID to a percentage dose equivalent of 150 mg diclofenac. ASAS-NSAID score = (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days). A negative change from baseline indicates less NSAID consumption.
  • Mean Change From Baseline in ASAS-NSAID Score in Each Secukinumab Group After 12 Weeks of Exposure (at Week 12 in the Secukinumab-delayed NSAID Tapering Group and at Week 16 in the Secukinumab-early NSAID Tapering Group) [ Time Frame: Baseline, Week 12 (delayed NSAID tapering), Week 16 (early NSAID tapering) ]
    ASAS-NSAID score is used to present the NSAID (nonsteroidal anti-inflammatory drug) intake by considering the type of NSAID, the total dose and the number of days taking NSAID during a period of interest (PI). For the NSAID equivalence scoring system, "no NSAID intake" was set to a score value of 0, and the reference dose of 150 mg/day diclofenac was set to a score value of 100. The Daily diclofenac-equivalent dose score was derived by converting each daily dose of NSAID to a percentage dose equivalent of 150 mg diclofenac. ASAS-NSAID score = (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days). A negative change from baseline indicates less NSAID consumption. For this endpoint the analysis was performed after 12 weeks of exposure to secukinumab which was achieved at Week 12 in the secukinumab delayed NSAID tapering group but at Week 16 in the secukinumab early NSAID tapering group.
  • Mean Change From Baseline in the BASDAI Total Score [ Time Frame: Baseline, Week 12, Week 16 ]
    The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to ankylosing spondylitis: 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (captured as a continuous visual analog scale). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe symptoms. A negative change from baseline in the total 0-10 BASDAI score indicates improvement.
  • Mean Change From Baseline in Health-related Quality of Life as Measured by the Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) Score [ Time Frame: Baseline, Week 12 ]
    The Short Form-36 Health Survey (SF-36) measures the impact of disease on overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36 (SF-36 PCS) that is evaluated in this study. Scores on each item 1-4 were summed and averaged (range = 0-100 with higher scores indicating better levels of function and/or better health). A positive change from Baseline indicates improvement.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2016)
  • Proportion of patients achieving an ASAS20 response [ Time Frame: Week 16 ]
    To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 with NSAID tapering allowed from week 4; early tapering) at Week 16 is superior to placebo based on the proportion of patients achieving an ASAS20 response.
  • Change from baseline in ASAS-NSAID score [ Time Frame: Week 12 ]
    To demonstrate that the change from baseline in ASAS-NSAID score at Week 12 is superior for Secukinumab 150 mg s.c. (Secukinumab from week 0 with NSAID tapering allowed from week 4; delayed tapering) as compared to placebo.
  • Change from baseline in ASAS-NSAID score [ Time Frame: Week 12 ]
    To demonstrate that the change from baseline in ASAS-NSAID score at Week 12 is superior for Secukinumab 150 mg s.c . (Secukinumab from week 4 with NSAID tapering allowed from week 4; early tapering) as compared to placebo.
  • Change from baseline in the total BASDAI [ Time Frame: Week 12 ]
    To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 0 with NSAID tapering allowed from week 4; delayed tapering) at Week 12 is superior to placebo based on the change from baseline in the total BASDAI.
  • Change from baseline in the total BASDAI [ Time Frame: Week 16 ]
    To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 with NSAID tapering allowed from week 4; early tapering) at Week 16 is superior to placebo based on the change from baseline in the total BASDAI.
  • Change from baseline in health-related Quality of Life as measured by the SF-36 Physical Component Score (PCS) [ Time Frame: Week 12 ]
    To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 0 with NSAID tapering allowed from week 4; delayed tapering) at Week 12 is superior to placebo based on the change from baseline in health-related Quality of Life as measured by the SF-36 Physical Component Score (PCS).
  • Change from baseline in health-related Quality of Life as measured by the SF-36 PCS [ Time Frame: Week 12 ]
    To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 with NSAID tapering allowed from week 4; early tapering) at Week 12 is superior to placebo based on the change from baseline in health-related Quality of Life as measured by the SF-36 PCS.
  • Change from baseline in ASAS-NSAID score [ Time Frame: Week 12 ]
    To compare between both Secukinumab regimens concerning the change from baseline in ASAS-NSAID score after 12 weeks of Secukinumab exposure (ASAS-NSAID index at Week 12 for delayed tapering vs. Week 16 for early tapering).
  • Change from baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [ Time Frame: Week 12 ]
    To compare between both Secukinumab regimens concerning the change from baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) after 12 weeks of Secukinumab exposure (BASDAI at Week 12 for delayed tapering vs. Week 16 for early tapering).
  • Change in patient reported neck, back and hip pain (BASDAI question 2) from baseline [ Time Frame: Week 0-12 ]
    To evaluate change in patient reported neck, back and hip pain (BASDAI question 2) from baseline on a continuous basis in patients randomized Secukinumab 150 mg s.c. (Secukinumab from week 0 with NSAID tapering allowed from week 4; delayed tapering) vs. placebo from week 0 to week 12.
  • Change in patient reported neck, back and hip pain (BASDAI question 2) from baseline [ Time Frame: Week 0-16 ]
    To evaluate change in patient reported neck, back and hip pain (BASDAI question 2) from baseline on a continuous basis in patients randomized Secukinumab 150 mg s.c. (early tapering) vs. placebo from week 0 to week 16.
  • Comparison of ASAS20 response rates [ Time Frame: Week 4 vs. Week 20 ]
    To compare ASAS20 response rates at week 4 in Secukinumab 150 mg. s.c. (Secukinumab from week 0 with NSAID tapering allowed from week 4; delayed tapering) vs. week 20 in the patients switching from Placebo after 4 weeks of Secukinumab exposure each.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Examine the Clinical Efficacy and the Nonsteroidal Anti-inflammatory Drug (NSAID)-Sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled Multicenter Study of Secukinumab (AIN457) to Examine the Clinical Efficacy and the NSAID-sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis (ASTRUM)
Brief Summary This study assessed the clinical Assessment of SpondyloArthritis international Society (ASAS) 20 response to secukinumab and evaluated to which extent concomitant nonsteroidal anti-inflammatory drug (NSAID) treatment can be reduced in patients treated with secukinumab or placebo following an initial run-in phase of stable NSAID therapy.
Detailed Description

This was a phase IV, 20-week, randomized, double-blind, 3-arm, placebo-controlled, parallel-group, multicenter study to examine the clinical response of secukinumab treatment in patients with ankylosing spondylitis as measured by the Assessment of SpondyloArthritis international Society (ASAS) 20 response and the nonsteroidal anti-inflammatory drug (NSAID)-sparing effect. This study evaluated to which extent nonsteroidal anti-inflammatory drug (NSAID) treatment can be reduced between Week 4 and Week 12 in patients randomized to secukinumab 150 mg or placebo following an initial run-in phase of 4 weeks on stable NSAID therapy. Two NSAID tapering approaches were evaluated in this study:

  1. an early tapering approach in which NSAID were tapered at the start of secukinumab treatment,
  2. a delayed tapering approach in which NSAID were tapered following 4 weeks of secukinumab treatment.

Patients were randomized 1:1:1 to one of the following treatment groups:

  • Secukinumab - delayed NSAID tapering: Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering).
  • Secukinumab - early NSAID tapering: Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering).
  • Placebo: Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4.

The primary objective of the study was to demonstrate that the efficacy of secukinumab 150 mg subcutaneous (s.c.) injection (with NSAID tapering) is superior to placebo based on the proportion of patients achieving an ASAS20 response at Week 12. To show superiority, both secukinumab treatment arms were pooled and compared against placebo.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ankylosing Spondylitis
Intervention  ICMJE
  • Drug: Secukinumab (AIN457) 150 mg s.c.
    Induction: 5 x 150 mg secukinumab s.c. weekly Maintenance: 4 x 150 mg secukinumab s.c. every 4 weeks Delayed NSAID tapering (tapering following 4 weeks of secukinumab treatment).
  • Drug: Secukinumab (AIN457) 150 mg s.c.
    Induction: 5 x 150 mg secukinumab s.c. weekly Maintenance: 3 x 150 mg secukinumab s.c. every 4 weeks Early NSAID tapering (tapering at the start of secukinumab treatment).
  • Drug: Placebo - Secukinumab (AIN457) 150 mg s.c.
    Placebo for 15 weeks. From Week 16 on, 5 x 150 mg secukinumab s.c. weekly.
Study Arms  ICMJE
  • Experimental: Secukinumab - delayed NSAID tapering

    Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind.

    NSAID tapering allowed from Week 4 (delayed tapering).

    Intervention: Drug: Secukinumab (AIN457) 150 mg s.c.
  • Experimental: Secukinumab - early NSAID tapering

    Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind.

    NSAID tapering allowed from Week 4 (early tapering).

    Intervention: Drug: Secukinumab (AIN457) 150 mg s.c.
  • Placebo Comparator: Placebo

    Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20).

    NSAID tapering allowed from Week 4.

    Intervention: Drug: Placebo - Secukinumab (AIN457) 150 mg s.c.
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 Completed
Actual Enrollment  ICMJE
 (submitted: April 30, 2019)
211
Original Estimated Enrollment  ICMJE
 (submitted: May 3, 2016)
204
Actual Study Completion Date  ICMJE September 24, 2019
Actual Primary Completion Date September 24, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Diagnosis of active AS with prior documented radiologic evidence fulfilling the Modified New York criteria for AS
  • Active AS assessed by total BASDAI ≥ 4 (0-10) at baseline
  • Spinal pain as measured by BASDAI Question 2 ≥ 4 cm on a 0-10 cm numeric rating scale at baseline
  • Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at baseline
  • Patients should have been on at least 2 different NSAIDs at the highest recommended dose for at least 4 weeks prior to randomization, with an inadequate response or failure to respond, or less if therapy had to be reduced due to intolerance, toxicity or contraindications
  • Patients must report regular intake of NSAIDs of at least 50% of the highest recommended dose at Screening.
  • Patients with prior TNFα inhibitor therapy must report regular intake of NSAIDs of at least 50% of the highest recommended dose at baseline after the appropriate washout
  • Patients are required to be on a stable dose of NSAIDs for at least 2 weeks before randomization
  • Patients who have previously been on a TNFα inhibitor will be allowed entry into study after an appropriate wash-out period prior to randomization
  • Patients who have been on a TNFα inhibitor (not more than two) must have experienced an inadequate response to previous or current treatment given at an approved dose for at least 3 months prior to randomization or have been intolerant to at least one administration of an anti-TNFα agent.
  • Patients taking MTX or sulfasalazine are allowed to continue their medication and must have taken it for at least 3 months and be on a stable dose for at least 4 weeks prior to randomization

Key Exclusion Criteria:

  • Chest X-ray or MRI with evidence of ongoing infectious or malignant process.
  • Previous exposure to Secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor
  • Patients previously treated with any biological immunomodulating agents, except those targeting TNFα
  • Patients who have taken more than two anti-TNFα agents
  • Pregnant or nursing (lactating) women.
  • History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection.
  • Patients who are intolerant to NSAIDs
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 Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02763046
Other Study ID Numbers  ICMJE CAIN457FDE03
2015-004575-74 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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