16-week Efficacy and 2-year Safety, Tolerability and Efficacy of Secukinumab in Participants With Active Ankylosing Spondylitis

Spondylitis, Ankylosing Clinical Trial

— MEASURE4  

Official title:

A Randomized, Double-blind, Placebo-controlled, Phase III Multicenter Study of Subcutaneous Secukinumab (150 mg) With and Without a Subcutaneous Loading Regimen to Assess Efficacy, Safety, and Tolerability up to 2 Years in Patients With Active Ankylosing Spondylitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02159053
• Other study ID #: CAIN457F2320
• Secondary ID: 2013-005575-41
• Status: Completed
• Phase: Phase 3
• Start date: May 18, 2015
• Est. completion date: January 2, 2018

Study information

• Verified date: November 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to provide 16-week efficacy, safety and tolerability data versus placebo to support the use of secukinumab 150 mg by subcutaneous (s.c.) self-administration with or without a loading regimen and maintenance dosing using pre-filled syringe (PFS) and to assess efficacy, safety and tolerability up to 2 years in subjects with active AS despite current or previous NSAID, non-biologic DMARD, or biologic anti-TNFα therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: January 2, 2018
• Est. primary completion date: February 23, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Spondylitis
• Spondylitis, Ankylosing

Intervention

Biological:
• Secukinumab
Eligible subjects are randomized to each of the three treatment arms in a 1:1:1 ratio
• Secukinumab
Eligible subjects are randomized to each of the three treatment arms in 1:1:1 ratio
• Placebo
Eligible subjects are randomized to each of the three treatment arms in a 1:1:1 ratio

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Hobart	Tasmania
Australia	Novartis Investigative Site	Kogarah	New South Wales
Australia	Novartis Investigative Site	Malvern East	Victoria
Australia	Novartis Investigative Site	Maroochydore	Queensland
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Vienna
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Targovishte
Canada	Novartis Investigative Site	Pointe-Claire	Quebec
Canada	Novartis Investigative Site	Trois Rivieres	Quebec
Canada	Novartis Investigative Site	Winnipeg	Manitoba
Czechia	Novartis Investigative Site	Ostrava	Czech Republic
Czechia	Novartis Investigative Site	Praha 11	Czech Republic
Czechia	Novartis Investigative Site	Praha 2	Czech Republic
Czechia	Novartis Investigative Site	Uherske Hradiste	Czech Republic
Denmark	Novartis Investigative Site	Frederiksberg
Denmark	Novartis Investigative Site	Odense
Finland	Novartis Investigative Site	Hyvinkaa
Finland	Novartis Investigative Site	Jyvaskyla
Germany	Novartis Investigative Site	Bad Doberan
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Germering
Germany	Novartis Investigative Site	Göttingen	Lower Saxony
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Wurzburg
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Patras
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Verona	VR
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Heerlen
Netherlands	Novartis Investigative Site	Leiden
Netherlands	Novartis Investigative Site	Rotterdam
Norway	Novartis Investigative Site	Kongsvinger
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Elblag
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Warszawa
Russian Federation	Novartis Investigative Site	Barnaul
Russian Federation	Novartis Investigative Site	Barnaul
Russian Federation	Novartis Investigative Site	Kemerovo
Russian Federation	Novartis Investigative Site	S.-Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	St-Petersburg
Slovakia	Novartis Investigative Site	Partizanske
Slovakia	Novartis Investigative Site	Piestany	SVK
Slovakia	Novartis Investigative Site	Sabinov
Slovakia	Novartis Investigative Site	Stara Lubovna
Slovakia	Novartis Investigative Site	Topolcany
Spain	Novartis Investigative Site	Baracaldo	Vizcaya
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Santander	Cantabria
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Switzerland	Novartis Investigative Site	Fribourg
Switzerland	Novartis Investigative Site	St Gallen
United Kingdom	Novartis Investigative Site	Doncaster
United Kingdom	Novartis Investigative Site	Leytonstone	London
United Kingdom	Novartis Investigative Site	Wolverhampton
United States	Novartis Investigative Site	Anniston	Alabama
United States	Novartis Investigative Site	Aventura	Florida
United States	Novartis Investigative Site	Columbia	South Carolina
United States	Novartis Investigative Site	Duncansville	Pennsylvania
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Mesquite	Texas
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Peoria	Illinois
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Shreveport	Louisiana
United States	Novartis Investigative Site	Upland	California
United States	Novartis Investigative Site	Voorhees	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Bulgaria,  Canada,  Czechia,  Denmark,  Finland,  Germany,  Greece,  Italy,  Netherlands,  Norway,  Poland,  Russian Federation,  Slovakia,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Responded for Assessment of Spondyloarthritis International Society 20 Criteria (ASAS20) at 16 Weeks	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 20 percent (%) and 1 unit on a scale of 10 in three main domains and no worsening of at least 20% and 1 unit on a scale of 10 in the fourth domain within a defined time frame. Four main ASAS domains include: 1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe 2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale 4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem)	16 Weeks
Secondary	Percentage of Participants Responded for ASAS 40 Response at 16 Weeks	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 40% and 2 unit on a scale of 10 in three main domains and no worsening at all in the remaining domain within a defined time frame. Four main ASAS domains include: Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe; Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain; Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale; Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).	16 Weeks
Secondary	Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at 16 Weeks	Blood levels of C-reactive protein (CRP) is an acute phase reactant, which are indicative of inflammation and of its severity, and can be used to monitor treatment response. A hsCRP test is implemented to assess the efficacy of secukinumab (with or without load) versus placebo in reducing ankylosing spondylitis elicited systemic inflammation over the time.	Baseline, 16 Weeks
Secondary	Percentage of Participants Responded for ASAS 5/6 Response at 16 Weeks	ASAS 5/6 response is a validated composite assessment, defined as an improvement of at least 20% in score in at least 5 of 6 clinical domains relevant to ankylosing spondylitis and no worsening in the remaining domain. ASAS domains includes: Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe; Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain; Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale; Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem); Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; C-reactive protein (CRP, acute phase reactant).	16 Weeks
Secondary	Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at 16 Weeks	BASDAI is a validated assessment tool using 0 through 10 scales (0 indicating "no problem" and 10 indicating "worst problem" on continuous VAS), to answer 6 questions (clinical domains) pertaining to 5 major symptoms of ankylosing spondylitis. Computed composite scores of 4 or greater indicate suboptimal disease control. BASDAI questions includes: Fatigue; Spinal pain; Joint pain / swelling; Areas of localized tenderness (called enthesitis, or inflammation of tendons and ligaments); Morning stiffness duration; Morning stiffness severity. Each symptom has equal weighting, the mean of two scores related to morning stiffness was taken (questions 5 and 6). The resulting 0 to 10 score was added to the scores from questions 1-4. The resulting 0 to 50 score was divided by 5 to give a final 0-10 BASDAI score. BASDAI was a quick and simple index taking between 30 seconds and 2 minutes for completion.	Baseline, 16 Weeks
Secondary	Change From Baseline in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36)	SF-36 is a 36 item questionnaire which measures Quality of Life across eight subscales that were scored individually: physical functioning, role- physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores are weighted sums of the questions in each section. Scores range from 0-100. Lower scores = more disability, higher scores = less disability. The overall summary scores, SF-36 physical Component Summary (PCS) was used to assess improvement from baseline in the Health-Related Quality Of Life of subjects. The change in SF-36 scores were evaluated using MMRM.	Baseline, 16 Weeks
Secondary	Change From Baseline in Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) at 16 Weeks	ASQoL is a self-administered 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 subject with ankylosing spondylitis: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score ranges from 0 (good QoL) to 18 (poor QoL). The change in ASQoL scores was evaluated using a mixed effect repeated measures model (MMRM).	Baseline, 16 Weeks
Secondary	Number of Participants With Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs) and Related Discontinuations at 104 Weeks	AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.	104 Weeks
Secondary	Percentage of Participants Responded for ASAS 20 at Week 4	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 20% and 1 unit on a scale of 10 in three main domains and no worsening of at least 20% and 1 unit on a scale of 10 in the fourth domain within a defined time frame. Four main ASAS domains include: Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe; Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain; Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale; Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).	Week 4
Secondary	Percentage of Participants Responded for ASAS 40 Response at Week 4	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 40% and 2 unit on a scale of 10 in three main domains and no worsening at all in the remaining domain within a defined time frame. Four main ASAS domains include: Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe; Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain; Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale; Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).	Week 4

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