16-week Efficacy and 3-year Safety, Tolerability and Efficacy of Secukinumab in Active Ankylosing Spondylitis Patients (MEASURE 3)

Study Description

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Brief Summary:

The purpose of this study is to generate 16-week efficacy data, as well as up to 3-year efficacy, safety and tolerability data in subjects with active AS despite current or previous NSAID, DMARD and/or anti-TNF therapy.

Condition or disease	Intervention/treatment	Phase
Spondylitis, Ankylosing	Drug: Secukinumab; Drug: Placebo secukinumab	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	226 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Randomized, Double-blind, Placebo-controlled Phase III Study of Secukinumab to Demonstrate the Efficacy at 16 Weeks and to Assess the Long-term Safety, Tolerability and Efficacy up to 3 Years in Subjects With Active Ankylosing Spondylitis
Actual Study Start Date :	January 14, 2014
Estimated Primary Completion Date :	December 12, 2017
Estimated Study Completion Date :	December 12, 2017

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Secukinumab 10 mg/kg i.v. / 300 mg s.c.; Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection every four weeks until the end of the study.	Drug: Secukinumab; Eligible patients are randomised to each of the three treatment arms in a 1:1:1 ratio.; Other Name: AIN457
Experimental: Secukinumab 10 mg/kg i.v. / 150 mg s.c.; Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection every four weeks until the end of the study.	Drug: Secukinumab; Eligible patients are randomised to each of the three treatment arms in a 1:1:1 ratio.; Other Name: AIN457
Placebo Comparator: Placebo i.v. and s.c.; Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection at weeks 8 and 12. At week 16, patients are re-randomised to one of the active treatment arms, to receive secukinumab s.c. Q4W until the end of the study.	Drug: Placebo secukinumab; Eligible patients are randomised to each of the three treatment arms in a 1:1:1 ratio.

Outcome Measures

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Primary Outcome Measures :

1. Assessment of Spondyloarthritis International Society criteria / ASAS 20 response [ Time Frame: 16 weeks ]
   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, ASAS 20 is used to assess the efficacy of at least one dose of secukinumab versus placebo.

Secondary Outcome Measures :

1. ASAS 40 response [ Time Frame: 16 weeks ]
   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, ASAS 40 is used to assess the efficacy of at least one dose of secukinumab versus placebo.
2. Serum hsCRP [ Time Frame: 16 weeks ]
   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 sensitivity 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 the time.
3. ASAS 5/6 response [ Time Frame: 16 weeks ]
   ASAS 5/6 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 5 of a conventional set of 6 clinical domains relevant to AS and no worsening in the remaining domain. In this study, ASAS 5/6 is used to assess the efficacy of at least one dose of secukinumab versus placebo.
4. Bath Ankylosing Spondylitis Disease Activity Index / BASDAI [ Time Frame: 16 weeks ]
   BASDAI is a validated assessment tool using 0 through 10 scales (0 indicating "no problem" and 10 indicating "worst problem"), to characterise 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, the BASDAI index is used to assess the efficacy of at least one dose of secukinumab versus placebo.
5. Pre-filled syringe usability, possible hazard and patient satisfaction assessment [ Time Frame: Baseline to week 16 ]
   The self-injection assessment questionnaire (SIAQ) is a tool to measure the overall patient experience with subcutaneous self-injection. It consists of a PRE module, administered before first self-injection and including items grouped into 3 hypothetical domains: feelings about injections, confidence to self-inject and satisfaction with current medication administration, and a POST module including items grouped into 6 hypothetical domains: in addition to the above, self-image with regard to self-injecting, injection-site reactions, ease of use of the PFS. Patients rate each item on a 5-level or a 6-level semantic Likert scale. These scores are transformed, to generate domain scores ranging from 0 (worst experience) to 10 (best experience). The Self-injection assessment checklist and the Possible hazard assessment checklist are observation questionnaires for non-directed querying about observed problems, device usability and patient capacity to follow written instruction for use.
6. Overall safety and tolerability [ Time Frame: 156 weeks ]
   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. During the first 16 weeks of the study, comparisons between the secukinumab treatment arms and the placebo treatment arm will also take place.
7. ASAS partial remission [ Time Frame: 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 of 10. In this study, ASAS partial remission is used to assess the efficacy of at least one dose of secukinumab versus placebo.

Eligibility Criteria

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

Criteria

Inclusion criteria: moderate to severe AS, prior radiographic evidence according to the Modified NY Criteria (1984), inadequate response to NSAIDs. -- Exclusion criteria: pregnancy or lactation, on-going infectious or malignant process on a chest X-ray or MRI, previous exposure to IL-17 or IL-17R targeting therapies, previous exposure to any biological immunomodulating agent excluding TNF antagonists, previous cell depleting therapy. -- Other protocol-defined inclusion/exclusion criteria do apply.

Contacts and Locations

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Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Introduction to clinical trials conducted by Novartis and to results of completed studies, with the aim of increasing the transparency of Novartis clinical research and making publicly available objective scientific information in a standardised format. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pavelka K, Kivitz A, Dokoupilova E, Blanco R, Maradiaga M, Tahir H, Pricop L, Andersson M, Readie A, Porter B. Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3. Arthritis Res Ther. 2017 Dec 22;19(1):285. doi: 10.1186/s13075-017-1490-y.

Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT02008916 History of Changes
Other Study ID Numbers:	CAIN457F2314; 2013-001090-24 ( EudraCT Number )
First Posted:	December 11, 2013
Last Update Posted:	April 21, 2017
Last Verified:	April 2017
Individual Participant Data (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

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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

AIN457, ankylosing spondylitis, chronic inflammatory disease, inflammatory back pain, secukinumab, self-injection

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