16-week Efficacy and 3-year Safety, Tolerability and Efficacy of Secukinumab in Active Ankylosing Spondylitis Patients - Full Text View

Purpose

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	Intervention	Phase
Spondylitis, Ankylosing	Drug: Secukinumab Drug: Placebo secukinumab	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Genetics Home Reference related topics: ankylosing spondylitis

MedlinePlus related topics: Ankylosing Spondylitis

Drug Information available for: Secukinumab

Genetic and Rare Diseases Information Center resources: Spondylarthropathy

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Assessment of Spondyloarthritis International Society criteria / ASAS 20 response [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
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:

ASAS 40 response [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
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.
Serum hsCRP [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
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.
ASAS 5/6 response [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
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.
Bath Ankylosing Spondylitis Disease Activity Index / BASDAI [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
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.
Pre-filled syringe usability, possible hazard and patient satisfaction assessment [ Time Frame: Baseline to week 16 ] [ Designated as safety issue: Yes ]
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.
Overall safety and tolerability [ Time Frame: 156 weeks ] [ Designated as safety issue: Yes ]
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.
ASAS partial remission [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
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.


Enrollment:	226
Study Start Date:	January 2014
Estimated Study Completion Date:	November 2017
Estimated Primary Completion Date:	November 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02008916

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Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

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. This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site


Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT02008916 History of Changes
Other Study ID Numbers:	CAIN457F2314 2013-001090-24
Study First Received:	December 8, 2013
Last Updated:	April 4, 2016
Health Authority:	United States: Food and Drug Administration Belgium: Federal Agency for Medicinal Products and Health Products Czech Republic: State Institute for Drug Control Germany: Paul-Ehrlich-Institut Greece: National Organization of Medicines Mexico: Federal Commission for Sanitary Risks Protection Norway: Norwegian Medicines Agency Portugal: National Pharmacy and Medicines Institute Russia: Ministry of Health of the Russian Federation United Kingdom: Medicines and Healthcare Products Regulatory Agency Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Novartis:


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

ClinicalTrials.gov processed this record on September 30, 2016

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