Effect of Secukinumab on Radiographic Progression in Ankylosing Spondylitis as Compared to GP2017 (Adalimumab Biosimilar)

Ankylosing Spondylitis Clinical Trial

— SURPASS  

Official title:

A Randomized, Partially-blinded Study of Secukinumab to Demonstrate Reduction of Radiographic Progression Versus GP2017 (Adalimumab Biosimilar) at 104 Weeks and to Assess the Long Term Safety, Tolerability and Efficacy up to 2 Years in Patients With Active Ankylosing Spondylitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03259074
• Other study ID #: CAIN457K2340
• Status: Completed
• Phase: Phase 3
• Start date: November 30, 2017
• Est. completion date: November 29, 2021

Study information

• Verified date: August 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to demonstrate the impact of secukinumab on the progression of structural damage in the spine, as measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) in patients with Ankylosing Spondylitis (AS).

Description:

This was a Phase IIIb, multi-center, randomized, partially-blinded, active-controlled, parallel-group design in subjects with AS. The study consisted of a screening period (up to 10 weeks before randomization), a treatment period (104 weeks), and two follow-up visits (Weeks 112 and 120). Subjects in both secukinumab dose groups received study treatment at baseline, Weeks 1, 2, 3 and 4 followed by treatment every 4 weeks through Week 100. Subjects in the GP2017 group received study treatment at baseline and every two weeks through Week 102. Subjects could self-administer all secukinumab / placebo and GP2017 doses at the study site or at home. Study treatment (secukinumab vs. GP2017) was provided in an open-label fashion. Subjects in the secukinumab groups were blinded to the dose (150 mg vs. 300 mg). Subjects who received rescue treatment with prohibited medications were allowed to remain in the study but had to discontinue study treatment. Subjects were treated for 104 weeks with two follow-up visits (Weeks 112 and 120). A total of 859 subjects were randomized to treatment at 171 sites in 30 countries in Europe, North America, South America, and Asia. .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 859
• Est. completion date: November 29, 2021
• Est. primary completion date: November 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or non-pregnant, non-nursing female patients at least 18 years of age
• Diagnosis of moderate to severe Ankylosing Spondylitis with radiologic evidence (centrally read X-ray) fulfilling the Modified New York criteria for AS despite previous or current NSAID/ nonbiologic DMARD therapy
• Active AS assessed by total BASDAI = 4 on a scale of 0-10
• Spinal pain as measured by BASDAI question #2 = 4 (0-10)
• Total back pain as measured by visual analog scale (VAS) = 40 mm (0-100 mm)
• hsCRP = 5 mg/L OR presence of at least 1 syndesmophyte on centrally read spinal X-ray

Exclusion Criteria:

• Patients with total ankylosis of the spine
• Pregnant or nursing (lactating) women
• Evidence of ongoing infectious or malignant process
• Previous exposure to any biologic immunomodulating agent, including those targeting IL-17, IL-17 receptor or TNFa
• Subjects taking high potency opioid analgesics
• Previous treatment with any cell-depleting therapies including but not limited to anti-CD20, investigational agents Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Spondylarthritis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

Biological:
• Placebo
Matching placebo to AIN457 150 mg dose administered with AIN457 via pre-filled syringes
• GP2017 (adalimumab biosimilar)
40 mg in pre-filled syringes was administered subcutaneously
• AIN457 150 mg
150 mg in pre-filled syringes was administered subcutaneously

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As
Australia	Novartis Investigative Site	Malvern East	Victoria
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Genk
Canada	Novartis Investigative Site	Barrie	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Trois Rivieres	Quebec
Canada	Novartis Investigative Site	Winnipeg	Manitoba
Chile	Novartis Investigative Site	Concepcion
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Santiago	RM
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bucaramanga	Santander
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Brno-Zidonice	CZE
Czechia	Novartis Investigative Site	Praha 11
Czechia	Novartis Investigative Site	Praha 2
Czechia	Novartis Investigative Site	Uherske Hradiste
Denmark	Novartis Investigative Site	Aalborg
Denmark	Novartis Investigative Site	Copenhagen
Finland	Novartis Investigative Site	Joensuu
France	Novartis Investigative Site	Boulogne Billancourt
France	Novartis Investigative Site	Le Mans
France	Novartis Investigative Site	Monaco
France	Novartis Investigative Site	Nice	Cedex1
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris Cedex 14
France	Novartis Investigative Site	Toulouse
Germany	Novartis Investigative Site	Bad Doberan
Germany	Novartis Investigative Site	Bayreuth
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Planegg
Germany	Novartis Investigative Site	Ratingen
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki	GR
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Tel Aviv
Japan	Novartis Investigative Site	Bunkyo ku	Tokyo
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Kita-gun	Kagawa
Japan	Novartis Investigative Site	Meguro	Tokyo
Japan	Novartis Investigative Site	Nankoku city	Kochi
Japan	Novartis Investigative Site	Nishinomiya	Hyogo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Tenri	Nara
Korea, Republic of	Novartis Investigative Site	Gwangju
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Mexico	Novartis Investigative Site	Culiacan	MEX
Mexico	Novartis Investigative Site	Mexicali	Baja California
Mexico	Novartis Investigative Site	Monterrey	Nuevo Leon
Mexico	Novartis Investigative Site	San Luis potosi
Mexico	Novartis Investigative Site	Torreon	Coahulia
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Leeuwarden
Netherlands	Novartis Investigative Site	Leiden	Zuid-Holland
Netherlands	Novartis Investigative Site	Maastricht
Netherlands	Novartis Investigative Site	Rotterdam
Peru	Novartis Investigative Site	Jesus Maria	Lima
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	San Isidro	Lima
Peru	Novartis Investigative Site	Santiago de Surco	Lima
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Quezon City
Philippines	Novartis Investigative Site	Quezon City
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Dopiewo
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Sopot
Portugal	Novartis Investigative Site	Almada
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Ponte de Lima
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Vila Nova de Gaia
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Cluj Napoca
Russian Federation	Novartis Investigative Site	Barnaul
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Ivanovo
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Kemerovo
Russian Federation	Novartis Investigative Site	Kemerovo
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Petrozavodsk
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	Ufa
Russian Federation	Novartis Investigative Site	Yaroslavl
Slovakia	Novartis Investigative Site	Bratislava	Slovak Republic
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Piestany	SVK
Slovakia	Novartis Investigative Site	Stara Lubovna
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Bilbao	Pais Vasco
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	San Vicente De Barakaldo	Bizkaia
Spain	Novartis Investigative Site	Santander	Cantabria
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Vigo	Pontevedra
Spain	Novartis Investigative Site	Villajoyosa	Alicante
Spain	Novartis Investigative Site	Vitoria	Vitoria Gasteiz
Taiwan	Novartis Investigative Site	Dalin
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Taichung	Taiwan ROC
Taiwan	Novartis Investigative Site	Taipei
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Eskisehir
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kocaeli
United Kingdom	Novartis Investigative Site	Bath
United Kingdom	Novartis Investigative Site	Bristol
United Kingdom	Novartis Investigative Site	Christchurch	Dorset
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	Leytonstone	London
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London	Edmonton
United Kingdom	Novartis Investigative Site	London	GBR
United Kingdom	Novartis Investigative Site	Norwich
United Kingdom	Novartis Investigative Site	Portsmouth	Hants
United Kingdom	Novartis Investigative Site	Stoke on Trent	Staffordshire
United Kingdom	Novartis Investigative Site	Torquay
United Kingdom	Novartis Investigative Site	Wolverhampton
United States	Novartis Investigative Site	Boise	Idaho
United States	Novartis Investigative Site	Dayton	Ohio
United States	Novartis Investigative Site	Duncansville	Pennsylvania
United States	Novartis Investigative Site	Escondido	California
United States	Novartis Investigative Site	Franklin	Wisconsin
United States	Novartis Investigative Site	Gainesville	Florida
United States	Novartis Investigative Site	Great Falls	Montana
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Kennewick	Washington
United States	Novartis Investigative Site	La Mesa	California
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Memphis	Tennessee
United States	Novartis Investigative Site	Mesa	Arizona
United States	Novartis Investigative Site	Mesquite	Texas
United States	Novartis Investigative Site	Middleburg Heights	Ohio
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	San Francisco	California
United States	Novartis Investigative Site	Shreveport	Louisiana
United States	Novartis Investigative Site	Wheaton	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  Chile,  Colombia,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Israel,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Peru,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With no Radiographic Progression at Week 104 (Multiple Imputation) (Full Analysis Set)	Radiographic progression was based on scores from the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The mSASSS is the sum of scores assessing the vertebral corners of the lumbar and cervical spine as 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), or 3 (bridging syndesmophyte) with a total range from 0-72. No radiographic progression was defined as the change from baseline in mSASSS score <= 0.5.	Baseline and at Week 104
Secondary	Change From Baseline in mSASSS at Week 104 (Multiple Imputation) (Full Analysis Set)	Radiographic changes in the spine were based on the change in score of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) from baseline to Week 104.; The mSASSS is the sum of scores assessing the vertebral corners of the lumbar and cervical spine as 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), or 3 (bridging syndesmophyte) with a total range from 0-72.	Baseline and at Week 104
Secondary	Percentage of Participants Without New Syndesmophytes by mSASSS Between Baseline and Week 104 (Multiple Imputation) (Syndesmophyte Subset)	Syndesmophytes are bony growths that develop on corner of the vertebrae of the spine which are indicators of AS. A participant was considered to have a syndesmophyte if at least one reader assessed vertebral corner as >= 2 at on the mSASSS scale at baseline. Only participants with a syndesmophyte at baseline were evaluated at Week 104 for new syndesmophytes. A new syndesmophyte was a syndesmophyte present at Week 104 which was not present at baseline. Absence of new syndesmophyte was defined as having individual vertebral score < 2 on the mSASSS scale for all interpretable locations that had no syndesmophyte at baseline. Missing responses for subjects without new syndesmophyte at Week 104 were imputed by multiple imputation (MCMC).	Baseline and at Week 104
Secondary	Change From Baseline in MRI Berlin Sacroiliac (SI) Joint Edema Score (Observed Data) (MRI Subset)	Magnetic Resonance Images (MRI) of the Sacroiliac Joint (SIJ) were assessed for the presence and severity of SIJ bone marrow edema according to the Berlin Active Inflammatory Lesions Scoring with a minimum score of 0 and a maximum score of 24. Higher scores indicate more inflammation.	Baseline and at Week 104
Secondary	Change From Baseline in Berlin Modification of ASspiMRI-a Edema Score (MRI Subset)	Magnetic Resonance Images (MRI) of the spine were assessed for the presence and severity of bone marrow edema in the spinal vertebrae according to the Berlin modification of the ASspiMRI-a edema score with a score range of 0 to 69. Higher scores indicate more inflammation.	Baseline and at Week 104
Secondary	Percentage of Responders for Assessment of SpondyloArthritis International Society 20 (ASAS20)	Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 4 domains measured on visual analog scales (VAS): 1. Patient's global assessment; 2. Patient's assessment of back pain; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). ASAS 20 response is defined as an improvement of =20% and =1 unit on a scale of 10 in at least three of the four main domains and no worsening of =20% and =1 unit on a scale of 10 in the remaining domain. A higher score on the VAS signifies higher severity.	Week 104
Secondary	Percentage of Responders for Assessment of SpondyloArthritis International Society 40 (ASAS 40)	Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 4 domains measured on visual analog scales (VAS): 1. Patient's global assessment; 2. Patient's assessment of back pain; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). ASAS40 response is defined as an improvement of =40% and =2 units on a scale of 10 in at least three of the four ASAS main domains and no worsening at all in the remaining domain. A higher score on the VAS signifies higher severity.	Week 104
Secondary	Percentage of Responders for Assessment of SpondyloArthritis International Society With a Partial Remission Response (Full Analysis Set)	The Assessment of SpondyloArthritis International Society (ASAS) partial remission response criteria consisted of the following assessment domains measured on visual analogue scales (VAS): 1. Patient's global assessment; 2. Patient's assessment of back pain; 3. Function represented by BASFI average of 10 questions regarding ability to perform specific tasks; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The ASAS partial remission criteria was defined as a value not above 2 units in each of the four domains on a scale of 10.	Week 104
Secondary	Percentage of Participants With Assessment of SpondyloArthritis International Society for Inactive Disease Response (Observed Data) (Full Analysis Set)	The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite index to assess disease activity in AS. Parameters used for the ASDAS include spinal pain (BASDAI question 2), the patient's global assessment of disease activity, peripheral pain/swelling (BASDAI question 3), duration of morning stiffness (BASDAI question 6) and C-reactive protein (CRP) in mg/L (Sieper 2009, Lukas 2009). Disease activity states are inactive disease, moderate disease activity, high disease activity, and very high disease activity. The 3 values selected to separate these states were < 1.3 between inactive disease and moderate disease activity, < 2.1 between moderate disease activity and high disease activity, and > 3.5 between high disease activity and very high disease activity. Selected cutoffs for improvement scores were a change = 1.1 unit for "minimal clinically important improvement" and a change = 2.0 units for "major improvement" (Machado 2011).	Week 104

External Links

•   A Plain Language Trial Summary is available on novctrd.com