We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03259074
Recruitment Status : Completed
First Posted : August 23, 2017
Results First Posted : March 9, 2023
Last Update Posted : March 9, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief 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).

Condition or disease Intervention/treatment Phase
Ankylosing Spondylitis Biological: Placebo Biological: GP2017 (adalimumab biosimilar) Biological: AIN457 150 mg Phase 3

Detailed 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.

.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 859 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Study was partially blinded. Subjects, investigators, site personnel, persons performing the assessments, monitors and the Sponsor remained blinded to the dose group of secukinumab (150 mg versus 300 mg)
Masking: Single (Outcomes Assessor)
Masking Description: The Participant, Care Provider, Investigator and Sponsor are blinded to Secukinumab dose
Primary Purpose: Treatment
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
Actual Study Start Date : November 30, 2017
Actual Primary Completion Date : November 12, 2021
Actual Study Completion Date : November 29, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: AIN457 150 mg/placebo
AIN457 150 mg and a matching placebo was administered subcutaneously via pre-filled syringes at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 100
 Biological: Placebo
Matching placebo to AIN457 150 mg dose administered with AIN457 via pre-filled syringes

Biological: AIN457 150 mg
150 mg in pre-filled syringes was administered subcutaneously
Other Name: secukinumab
Experimental: AIN457 300 mg
AIN457 300 mg (2 x 150 mg) was administered subcutaneously via pre-filled syringes at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 100
 Biological: AIN457 150 mg
150 mg in pre-filled syringes was administered subcutaneously
Other Name: secukinumab
Active Comparator: GP2017 40mg
GP2017 (adalimumab biosimilar) 40 mg was administered subcutaneously via pre-filled syringes at Baseline followed by dosing every 2 weeks until Week 102
 Biological: GP2017 (adalimumab biosimilar)
40 mg in pre-filled syringes was administered subcutaneously
Other Name: adalimumab biosimilar


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Percentage of Participants With no Radiographic Progression at Week 104 (Multiple Imputation) (Full Analysis Set) [ Time Frame: Baseline and at Week 104 ]
    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.


Secondary Outcome Measures :
  1. Change From Baseline in mSASSS at Week 104 (Multiple Imputation) (Full Analysis Set) [ Time Frame: Baseline and at Week 104 ]

    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.


  2. Percentage of Participants Without New Syndesmophytes by mSASSS Between Baseline and Week 104 (Multiple Imputation) (Syndesmophyte Subset) [ Time Frame: Baseline and at Week 104 ]
    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).

  3. Change From Baseline in MRI Berlin Sacroiliac (SI) Joint Edema Score (Observed Data) (MRI Subset) [ Time Frame: Baseline and at Week 104 ]
    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.

  4. Change From Baseline in Berlin Modification of ASspiMRI-a Edema Score (MRI Subset) [ Time Frame: Baseline and at Week 104 ]
    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.

  5. Percentage of Responders for Assessment of SpondyloArthritis International Society 20 (ASAS20) [ Time Frame: Week 104 ]
    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.

  6. Percentage of Responders for Assessment of SpondyloArthritis International Society 40 (ASAS 40) [ Time Frame: Week 104 ]
    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.

  7. Percentage of Responders for Assessment of SpondyloArthritis International Society With a Partial Remission Response (Full Analysis Set) [ Time Frame: Week 104 ]
    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.

  8. Percentage of Participants With Assessment of SpondyloArthritis International Society for Inactive Disease Response (Observed Data) (Full Analysis Set) [ Time Frame: Week 104 ]
    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).


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 TNFα
  • 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

Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03259074


Locations
Show Show 171 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] February 4, 2021
Statistical Analysis Plan  [PDF] May 10, 2022

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03259074    
Other Study ID Numbers: CAIN457K2340
First Posted: August 23, 2017    Key Record Dates
Results First Posted: March 9, 2023
Last Update Posted: March 9, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
ankylosing spondylitis
AS
secukinumab
GP2017
adalimumab biosimilar
mSASSS
ASAS20
 ASAS40
adult
r-axSpA
AIN457
radiographic
SURPASS
Additional relevant MeSH terms:
Layout table for MeSH terms
Spondylitis
Spondylarthritis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infections
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Arthritis
 Joint Diseases
Axial Spondyloarthritis
Spondylarthropathies
Ankylosis
Adalimumab
Tumor Necrosis Factor Inhibitors
Anti-Inflammatory Agents
Antirheumatic Agents