16 Week Efficacy and 5 Year Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Ankylosing Spondylitis (MEASURE2)

• ClinicalTrials.gov Identifier: NCT01649375
• Recruitment Status: Completed
• First Posted: July 25, 2012
• Results First Posted: October 30, 2019
• Last Update Posted: October 30, 2019
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: July 20, 2012
• First Posted Date: July 25, 2012
• Results First Submitted Date: July 24, 2019
• Results First Posted Date: October 30, 2019
• Last Update Posted Date: October 30, 2019
• Actual Study Start Date: October 18, 2012
• Actual Primary Completion Date: August 4, 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 28, 2019)

Percentage of Participants Achieving ASAS 20 (SpondyloArthritis International Society Criteria) Response at Week 16 [ Time Frame: Baseline up to 16 weeks ]

ASAS 20 response is a validated composite assessment reflecting the percentage of treated patients who achieve within a defined timeframe an improvement of 20% and ≥1 unit on a scale of 1 to 10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit in the remaining domain. ASAS 20 is used to assess the efficacy of at least one dose of secukinumab against placebo.

Original Primary Outcome Measures (submitted: July 24, 2012)

Proportion of subjects achieving ASAS 20 response at week 16 [ Time Frame: 16 weeks ]

Primary endpoint is proportion of subjects achieving an ASAS 20 (Assessment of SpondyloArthritis International Society criteria) response at week 16 in subgroup of patients who are TNFα inhibitor naïve compared to placebo. ASAS Response Criteria is defined as an improvement of at least 20% and absolute improvement of at least 10 units on a 0-100mm scale in at least 3 of 4 assessment domains (1. subject's global assessment of disease activity 2. subject's assessment of inflammatory back pain 3. function represented by BASFI VAS 4. morning stiffness represented by the last 2 questions on BASDAI)

Current Secondary Outcome Measures (submitted: October 28, 2019)

• Percentage of Participants Achieving ASAS 40 (SpondyloArthritis International Society Criteria) Response [ Time Frame: Baseline up to 16 weeks ]
  ASAS 40 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe an improvement of ≥40% and ≥2 units on a scale of 0 to 10 (0 being worse and 10 being better) in at least three of the four ASAS main domains (patient global, pain, function and inflammation) and no worsening at all in the remaining domain. ASAS 40 is used to assess the efficacy of at least one dose of secukinumab against placebo.
• Change From Baseline at Week 16 in Serum hsCRP [ Time Frame: Baseline up to 16 weeks ]
  The change from baseline in hsCRP is expressed as a ratio of post-baseline to baseline values. With the ratio normalized to 1.0 at baseline, ratios less than 1.0 represent decreased post-baseline values, whereas ratios greater than 1.0 represent increased post-baseline values. Blood levels of C-reactive protein (CRP), an acute phase reactant, are indicative of inflammation and of its severity, and can be used to monitor treatment response. A high sensitvity CRP (hsCRP) test is implemented in this study to assess the efficacy of at least one dose of secukinumab versus placebo in reducing AS elicited systemic inflammation over time.
• Percentage of Participants Achieving ASAS 5/6 (SpondyloArthritis International Society Criteria) Response at Week 16 [ Time Frame: Baseline up to 16 weeks ]
  ASAS 5/6 response is a validated composite assessment, reflecting the percentage of treated patients who achieve within a defined timeframe at least 20% improvement in score in at least 5 of a conventional set of 6 clinical domains relevant to AS (pain, patient global assessment, function, inflammation, spinal mobility, C-reative protein) without deterioration in the 6th domain. In this study, ASAS 5/6 is used to assess the efficacy of at least one dose of secukinumab against placebo.
• Change From Baseline at Week 16 for Total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [ Time Frame: Baseline up to 16 weeks ]
  BASDAI is a validated assessment tool using 1 through 10 scales (1 indicating "no problem" and 10 indicating " worst problem"), to characterize six clinical domains (fatigue, spinal pain, joint pain/selling, localized tenderness, morning stiffness duration, morning stiffness severity) 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, the BASDAI is used to assess the efficacy of at least one dose of secukinumab verus placebo.
• Change From Baseline at Week 16 in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36) [ Time Frame: Baseline up to 16 weeks ]
  Physical Function Component Summary (PCS) is only 1 component of SF-36. This scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
• Change From Baseline at Week 16 in ASQoL [ Time Frame: Baseline up to 16 weeks ]
  ASQoL is an 18 item questionnaire that assesses disease-specific quality of life (QoL), consisting of statements that are relevant to the physical and mental conditions for a participant with AS: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered by the participant as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score can range from 0 (good QoL) to 18 (poor QoL). In this study, ASQoL is used to assess improvement from baseline of at least one dose of secukinumab versus placebo.
• Percentage of Participants Achieving ASAS Partial Remission at Week 16 [ Time Frame: Baseline up to 16 weeks ]
  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 0 to 10. In this study ASAS partial remission is used to assess the efficacy of at least one dose of secukinumab versus placebo.

Original Secondary Outcome Measures (submitted: July 24, 2012)

• Proportion of subjects achieving ASAS 20 response at week 16 in whole study population [ Time Frame: 16 weeks ]
  Proportion of patients achieving an ASAS 20 response in the whole study population compared to placebo at week 16. The ASAS Response Criteria is defined as an improvement of at least 20% and absolute improvement of at least 10 units on a 0-100mm scale in at least 3 of 4 assessment domains (1. subject's global assessment of disease activity 2. subject's assessment of inflammatory back pain 3. function represented by BASFI VAS 4. morning stiffness represented by the last 2 questions on BASDAI)
• Proportion of subjects achieving ASAS 40 response at week 16 [ Time Frame: 16 weeks ]
  Proportion of subjects achieving an ASAS 40 response at week 16 in subgroup of patients who are TNFα inhibitor naïve compared to placebo. ASAS Response Criteria is defined as an improvement of at least 40% and absolute improvement of at least 10 units on a 0-100mm scale in at least 3 of 4 assessment domains (1. subject's global assessment of disease activity 2. subject's assessment of inflammatory back pain 3. function represented by BASFI VAS 4. morning stiffness represented by the last 2 questions on BASDAI)
• Proportion of subjects achieving ASAS 40 response at week 16 in whole study population [ Time Frame: 16 weeks ]
  Proportion of patients achieving an ASAS 40 response in the whole study population compared to placebo at week 16. The ASAS Response Criteria is defined as an improvement of at least 40% and absolute improvement of at least 10 units on a 0-100mm scale in at least 3 of 4 assessment domains (1. subject's global assessment of disease activity 2. subject's assessment of inflammatory back pain 3. function represented by BASFI VAS 4. morning stiffness represented by the last 2 questions on BASDAI)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 16 Week Efficacy and 5 Year Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Ankylosing Spondylitis
• Official Title: A Randomized, Double-blind, Placebo-controlled Phase III Study of Subcutaneous Secukinumab in Prefilled Syringes to Demonstrate Efficacy at 16 Weeks and to Assess Long-term Efficacy, Safety and Tolerability up to 5 Years in Patients With Active Ankylosing Spondylitis
• Brief Summary: This study assessed the efficacy and safety of secukinumab in patients with active ankylosing spondylitis who were tolerant to or had an inadequate response to NSAIDs, DMARDs and / or TNFα inhibitor
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Anklyosing Spondylitis

Intervention

• Drug: Secukinumab (75 mg)
  Secukinumab 75 mg s.c.
  Other Name: AIN457 75 mg
• Drug: Placebo
  Placebo
• Drug: Secukinumab (150 mg)
  Secukinumab 150 mg s.c.
  Other Name: AIN457 150 mg

Study Arms

• Experimental: Secukinumab 75 mg
  Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.
  Intervention: Drug: Secukinumab (75 mg)
• Experimental: Secukinumab 150 mg
  Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks
  Intervention: Drug: Secukinumab (150 mg)
• Placebo Comparator: Placebo
  Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks
  Intervention: Drug: Placebo

Publications *

• Baraliakos X, Van den Bosch F, Machado PM, Gensler LS, Marzo-Ortega H, Sherif B, Quebe-Fehling E, Porter B, Gaillez C, Deodhar A. Achievement of Remission Endpoints with Secukinumab Over 3 Years in Active Ankylosing Spondylitis: Pooled Analysis of Two Phase 3 Studies. Rheumatol Ther. 2020 Dec 22. doi: 10.1007/s40744-020-00269-6. [Epub ahead of print]
• Deodhar AA, Miceli-Richard C, Baraliakos X, Marzo-Ortega H, Gladman DD, Blanco R, Das Gupta A, Martin R, Safi J Jr, Porter B, Shete A, Rosenbaum JT. Incidence of Uveitis in Secukinumab-treated Patients With Ankylosing Spondylitis: Pooled Data Analysis From Three Phase 3 Studies. ACR Open Rheumatol. 2020 May;2(5):294-299. doi: 10.1002/acr2.11139. Epub 2020 Apr 30.
• Deodhar A, Gladman DD, McInnes IB, Spindeldreher S, Martin R, Pricop L, Porter B, Safi J Jr, Shete A, Bruin G. Secukinumab Immunogenicity over 52 Weeks in Patients with Psoriatic Arthritis and Ankylosing Spondylitis. J Rheumatol. 2020 Apr;47(4):539-547. doi: 10.3899/jrheum.190116. Epub 2019 Jun 15.
• Braun J, Deodhar A, Landewé R, Baraliakos X, Miceli-Richard C, Sieper J, Quebe-Fehling E, Martin R, Porter B, Gandhi KK, van der Heijde D; MEASURE 1 and MEASURE 2 study groups. Impact of baseline C-reactive protein levels on the response to secukinumab in ankylosing spondylitis: 3-year pooled data from two phase III studies. RMD Open. 2018 Nov 21;4(2):e000749. doi: 10.1136/rmdopen-2018-000749. eCollection 2018.
• Wei JC, Baeten D, Sieper J, Deodhar A, Bhosekar V, Martin R, Porter B. Efficacy and safety of secukinumab in Asian patients with active ankylosing spondylitis: 52-week pooled results from two phase 3 studies. Int J Rheum Dis. 2017 May;20(5):589-596. doi: 10.1111/1756-185X.13094. Epub 2017 May 25. Erratum in: Int J Rheum Dis. 2017 Jul;20(7):911.
• Marzo-Ortega H, Sieper J, Kivitz A, Blanco R, Cohen M, Martin R, Readie A, Richards HB, Porter B; Measure 2 Study Group. Secukinumab and Sustained Improvement in Signs and Symptoms of Patients With Active Ankylosing Spondylitis Through Two Years: Results From a Phase III Study. Arthritis Care Res (Hoboken). 2017 Jul;69(7):1020-1029. doi: 10.1002/acr.23233. Epub 2017 Jun 7.
• Sieper J, Deodhar A, Marzo-Ortega H, Aelion JA, Blanco R, Jui-Cheng T, Andersson M, Porter B, Richards HB; MEASURE 2 Study Group. Secukinumab efficacy in anti-TNF-naive and anti-TNF-experienced subjects with active ankylosing spondylitis: results from the MEASURE 2 Study. Ann Rheum Dis. 2017 Mar;76(3):571-592. doi: 10.1136/annrheumdis-2016-210023. Epub 2016 Aug 31.
• Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, Deodhar A, Porter B, Martin R, Andersson M, Mpofu S, Richards HB; MEASURE 1 Study Group; MEASURE 2 Study Group. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015 Dec 24;373(26):2534-48. doi: 10.1056/NEJMoa1505066.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 20, 2017): 219
• Original Estimated Enrollment (submitted: July 24, 2012): 222
• Actual Study Completion Date: September 18, 2018
• Actual Primary Completion Date: August 4, 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or non-pregnant, non-lactating female patients
• Diagnosis of moderate to severe AS with prior documented radiologic evidence (x-ray) fulfilling the Modified New York criteria for AS (1984)
• Patients should have been on NSAIDs with an inadequate response
• Patients who were regularly taking NSAIDs as part of their AS therapy are required to be on a stable dose
• Patients who had been on an anti-TNFα agent (not more than one) must have experienced an inadequate response

Exclusion Criteria:

• Chest X-ray (or MRI) with evidence of ongoing infectious or malignant process
• Patients with total ankylosis of the spine
• Patients previously treated with any biological immunomodulating agents except for those targeting TNFα
• Previous treatment with any cell-depleting therapies

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Canada, Czechia, Finland, Germany, Italy, Netherlands, Russian Federation, Singapore, Spain, Switzerland, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01649375
• Other Study ID Numbers: CAIN457F2310; 2012-000046-35 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

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

• Plan to Share IPD: Undecided

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect 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: Novartis Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: October 2019