Efficacy and Safety Study of Secukinumab in Chinese Participants With Non-radiographic Axial Spondyloarthritis

A Randomized, Double-blind, Placebo Controlled, Multicenter, Phase III Study of Subcutaneous Secukinumab to Compare Efficacy at 16 Weeks With Placebo and to Assess Safety and Tolerability up to 52 Weeks in Chinese Participants With Active Non-radiographic Axial Spondyloarthritis

The purpose of this study was to evaluate the efficacy, safety, and tolerability of secukinumab in Chinese patients with active non-radiographic axial spondyloarthritis (nr-axSpA).

Study Overview

• Status: Completed
• Conditions: Non-radiographic Axial Spondyloarthritis
• Intervention / Treatment: Drug: Secukinumab; Drug: Placebo

Detailed Description

This was a randomized, double-blind, placebo-controlled study. Approximately 134 participants were planned to be randomized in a 1:1 ratio to receive secukinumab 150 mg subcutaneously (s.c.) or placebo.

The double-blind treatment period lasted for 16 weeks. At the end of this period, all participants, including those who initially received placebo, switched to open-label treatment with secukinumab 150 mg s.c.

The first dose of open-label treatment was administered at the Week 16 visit, after completing all necessary assessments for that visit. However, the participants and investigators remained blinded to the original treatment assignment. At Week 24, participants who did not respond to the treatment (defined as not achieving Ankylosing SpondyloArthritis International Society 20 [ASAS20] response) were given a higher dose of secukinumab (300 mg s.c.), while responders continued with the 150 mg s.c. dose. The study treatment continued until Week 48. Four weeks after the last study treatment administration, an end-of-treatment visit was conducted at Week 52.

Additionally, a post-treatment safety follow-up visit was performed 12 weeks after the last study treatment administration for all participants, whether they completed the entire study as planned or exited early.

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100050
    • Novartis Investigative Site
  • Beijing, China, 100000
    • Novartis Investigative Site
  • Bengbu, China, 233004
    • Novartis Investigative Site
  • Shanghai, China, 200040
    • Novartis Investigative Site
  • Shanghai, China, 200050
    • Novartis Investigative Site
  • Tianjin, China, 300052
    • Novartis Investigative Site
  • Anhui
    • Hefei, Anhui, China, 230001
      • Novartis Investigative Site
    • Hefei, Anhui, China, 230601
      • Novartis Investigative Site
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100044
      • Novartis Investigative Site
  • Fujian
    • Xiamen, Fujian, China, 361001
      • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510030
      • Novartis Investigative Site
    • Guangzhou, Guangdong, China, 510515
      • Novartis Investigative Site
    • Shantou, Guangdong, China, 515000
      • Novartis Investigative Site
    • Shenzhen, Guangdong, China, 518020
      • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Novartis Investigative Site
  • Hunan
    • Changsha, Hunan, China, 410011
      • Novartis Investigative Site
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014010
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Novartis Investigative Site
    • Nanjing, Jiangsu, China, 210009
      • Novartis Investigative Site
    • Yangzhou, Jiangsu, China, 225001
      • Novartis Investigative Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Novartis Investigative Site
    • Pingxiang, Jiangxi, China, 337000
      • Novartis Investigative Site
  • Jilin
    • Changchun, Jilin, China, 130021
      • Novartis Investigative Site
  • Shandong
    • Linyi, Shandong, China, 276000
      • Novartis Investigative Site
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830001
      • Novartis Investigative Site
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Novartis Investigative Site
  • Zhejiang
    • Ningbo, Zhejiang, China, 315016
      • Novartis Investigative Site
    • Wenzhou, Zhejiang, China, 325000
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or non-pregnant, non-nursing female patients at least 18 years of age
• Diagnosis of axial spondyloarthritis according to Ankylosing SpondyloArthritis International Society (ASAS) axial spondyloarthritis criteria
• Objective signs of inflammation (magnetic resonance imaging (MRI) or abnormal C-reactive protein)
• Active axial spondyloarthritis as assessed by total Bath Ankylosing Spondylitis Disease Activity Index >=4 cm
• Spinal pain as measured by Bath Ankylosing Spondylitis Disease Activity Index question #2 ≥ 4 cm (0-10 cm) at baseline
• Total back pain as measured by Visual Analogue scale ≥ 40 mm (0-100 mm) at baseline
• Patients should have been on at least 2 different non-steroidal anti-inflammatory drugs with an inadequate response
• Patients who have been on a TNFα inhibitor (not more than one) must have experienced an inadequate response

Exclusion Criteria:

• Patients with radiographic evidence for sacroiliitis, grade ≥ 2 bilaterally or grade ≥ 3 unilaterally
• Inability or unwillingness to undergo MRI
• Chest X-ray or MRI with evidence of ongoing infectious or malignant process
• Patients taking high potency opioid analgesics
• Previous exposure to secukinumab or any other biologic drug directly targeting interleukin-17 (IL-17) or IL-17 receptor
• Pregnant or nursing (lactating) women

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Secukinumab; Participants received secukinumab 150 mg in a pre-filled syringe (PFS). Treatment was double-blinded until Week 12. From Week 16, participants continued with an open-label treatment of secukinumab 150 mg. At Week 24, non-responders (not achieving ASAS20) were escalated to secukinumab 300 mg, while responders continued with secukinumab 150 mg.	Drug: Secukinumab; Secukinumab 150 mg s.c. using a PFS at Baseline, Weeks 1, 2, and 3, followed by administration every 4 weeks from Week 4 until Week 12. At Week 16, all participants continued or switched to receiving secukinumab 150 mg s.c. every 4 weeks, using a PFS. This treatment regimen continued from Week 16 through Week 48. For participants who did not respond to the secukinumab 150 mg dose during the open-label period, the dose was increased to 300 mg s.c., using two PFS, also administered every 4 weeks.; Other Names: AIN457
Placebo Comparator: Placebo; Participants initially received a placebo in a pre-filled syringe (PFS) in a double-blinded manner until Week 12. At Week 16, they switched to an open-label treatment of secukinumab 150 mg. At Week 24, non-responders (not achieving ASAS20) were escalated to secukinumab 300 mg, while responders continued with secukinumab 150 mg.	Drug: Placebo; Placebo s.c. using a PFS at baseline, Weeks 1, 2 and 3, followed by administration every 4 weeks from Week 4 until Week 12.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of SpondyloArthritis International Society 40 (ASAS40) Response Rate in TNF-alpha-inhibitor-naive Participants at Week 16	ASAS40 response was defined as relative improvement of at least 40% and absolute improvement of at least 2 units on a 0 to 10 scale in at least 3 of the 4 main domains of the ASAS and no worsening at all in the remaining domain. The 4 main domains of the ASAS are: 1.Patient's Global Assessment of Disease Activity (score ranged from 0 [not active] to 10 [very active]); 2.Back Pain (score ranged from 0 [no pain] to 10 [severe pain]); 3.Function (Bath Ankylosing Spondylitis Functional Index [BASFI]) (score ranged from 0 [easy] to 10 [impossible]); 4.Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) (score ranged from 0 [none] to 10 [very severe]). The percentage of TNF-alpha-inhibitor-naïve participants who achieved ASAS40 response at Week 16 was assessed using a logistic regression model. Discontinued participants and those with missing responses were considered non-responders	Baseline, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ASAS40 Response Rate in All Participants at Week 16	ASAS40 response was defined as relative improvement of at least 40% and absolute improvement of at least 2 units on a 0 to 10 scale in at least 3 of the 4 main domains of the ASAS and no worsening at all in the remaining domain. The 4 main domains of the ASAS are: 1.Patient's Global Assessment of Disease Activity (score ranged from 0 [not active] to 10 [very active]); 2.Back Pain (score ranged from 0 [no pain] to 10 [severe pain]); 3.Function (BASFI) (score ranged from 0 [easy] to 10 [impossible]); 4.Inflammation (mean of BASDAI questions 5 and 6 concerning morning stiffness intensity and duration) (score ranged from 0 [none] to 10 [very severe]). The percentage of participants who achieved ASAS40 response at Week 16 was assessed using a logistic regression model. Discontinued participants and those with missing responses were considered non-responders	Baseline, Week 16
ASAS 5/6 Response Rate at Week 16.	The ASAS 5/6 response was defined as an improvement of ≥20% in at least five of all six domains of the ASAS: 1.Patient's Global Assessment of Disease Activity (score ranged from 0 [not active] to 10 [very active]); 2.Back Pain (score ranged from 0 [no pain] to 10 [severe pain]); 3.Function (BASFI) (score ranged from 0 [easy] to 10 [impossible]); 4.Inflammation (mean of BASDAI questions 5 and 6 concerning morning stiffness intensity and duration) (score ranged from 0 [none] to 10 [very severe]); 5) spinal mobility represented by the BAS Disease Metrology Index (BASDMI) (scale ranged from 0 [no limitation of movement] to 10 [very severe limitation of movement]; and 6) C-reactive protein (acute phase reactant). The percentage of participants who achieved ASAS 5/6 response at Week 16 was assessed using a logistic regression model. Missing responses were imputed as non-responders. Discontinued participants were considered non-responders	Baseline, Week 16
Change From Baseline in Total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score at Week 16	The BASDAI consisted of a 0 through 10 scale (0 being no problem and 10 being the worst problem, captured as a continuous VAS), which was used to answer 6 questions pertaining to the 5 major symptoms of AS: 1. Fatigue; 2. Spinal pain; 3. Joint pain / swelling; 4. Areas of localized tenderness (called enthesitis, or inflammation of tendons and ligaments); 5. Morning stiffness duration; 6. Morning stiffness severity. BASDAI score was calculated as the mean of the 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, where higher score indicated high disease activity. The change from baseline in BASDAI scores at Week 16 was assessed using Mixed-effects model repeated measures (MMRM). A negative change from baseline indicated improvement.	Baseline, Week 16
BASDAI 50 Rate at Week 16	The BASDAI consisted of a 0 through 10 scale (0 being no problem and 10 being the worst problem, captured as a continuous VAS), which was used to answer 6 questions pertaining to the 5 major symptoms of AS: 1. Fatigue; 2. Spinal pain; 3. Joint pain / swelling; 4. Areas of localized tenderness (called enthesitis, or inflammation of tendons and ligaments); 5. Morning stiffness duration; 6. Morning stiffness severity. BASDAI score was calculated as the mean of the 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, where higher score indicated high disease activity. BASDAI 50 was defined as an improvement of at least 50% in the BASDAI total score compared to baseline. The percentage of participants achieving BASDAI 50 at Week 16 was assessed using a logistic regression model. Discontinued participants and with missing responses were considered non-responders	Baseline, Week 16
Change From Baseline of High Sensitivity C-Reactive Protein (hsCRP) at Week 16	hsCRP was measured as a marker of inflammation from blood samples. The change from baseline in hsCRP at Week 16 was assessed using MMRM. It was expressed as a ratio of Week 16 to baseline values. Ratios less than 1.0 at Week 16 represented reduced hsCRP.	Baseline, Week 16
Change From Baseline in Total Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16	The BASFI is a set of 10 questions designed to determine the degree of functional limitation in subjects with AS. The questions were chosen on the basis of predominant input from subjects with AS. The first eight questions consider activities related to functional anatomy. The final two questions assess the subjects' ability to cope with everyday life. A 0-10 scale (captured as a continuous VAS) is used to answer the questions. The BASFI score is the mean of the ten scales - a value between 0 and 10, with higher scores indicating a higher degree of functional limitation in patients. The change from baseline in BASFI at Week 16 was assessed. A negative change from baseline indicated improvement.	Baseline, Week 16
Change From Baseline in Sacroiliac Joint (SIJ) Edema Score on Magentic Resonance Imaging (MRI) at Week 16	The MRI assessment of the total edema score of the Sacroiliac Joint (SIJ) measured the degree of edema or fluid accumulation in the joint. The score ranged from 0 to 24, with higher scores indicating more severe inflammation. The change from baseline in inflammation, as measured by the SI joint total edema score at Week 16, was evaluated using an ANCOVA model. Any missing data was imputed using multiple imputation prior to running the ANCOVA analysis.	Baseline, Week 16
ASAS20 Response Rate at Week 16	ASAS20 response was defined as relative improvement of at least 20% and absolute improvement of at least 1 unit on a 0 to 10 scale in at least 3 of the 4 main domains of the ASAS and no worsening of ≥20% and ≥1 unit at all in the remaining domain. The 4 main domains of ASAS are 1.Patient's Global Assessment of Disease Activity (score ranged from 0 [not active] to 10 [very active]); 2.Back Pain (score ranged from 0 [no pain] to 10 [severe pain]); 3.Function (BASFI) (score ranged from 0 [easy] to 10 [impossible]); 4.Inflammation (mean of BASDAI questions 5 and 6 concerning morning stiffness intensity and duration) (score ranged from 0 [none] to 10 [very severe]) The percentage of participants who achieved ASAS20 response at Week 16 was assessed using a logistic regression model. Discontinued participants and those with missing responses were considered non-responders	Baseline, Week 16
Change From Baseline in Short Form-36 Physical Component Summary (SF-36 PCS) at Week 16	SF-36 was an instrument used to measure health-related quality of life among healthy patients and patients with acute and chronic conditions. It consisted of eight subscales (domains) that could be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role- Emotional, and Mental Health. Each domain score ranged from 0 to 100, with higher scores indicating a higher level of functioning. The Physical Component Summary (PCS) was an overall summary score calculated from the 8 domains. It was a norm-based score with a mean of 50 and a standard deviation of 10. Higher scores indicated a higher level of functioning. The change from baseline in PCS at Week 16 was evaluated using MMRM. A positive change from baseline indicated an improvement.	Baseline, Week 16
Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Scores at Week 16	The ASQoL was a self-administered questionnaire designed to assess health-related quality of life (HRQoL) in participants with ankylosing spondylitis. The ASQoL contained 18 items with a dichotomous yes/no response option. A single point was assigned for each "yes" response and no points for each "no" response resulting in overall scores that ranged from 0 (least severity) to 18 (highest severity). As such, a lower score indicated a better quality of life. Items included an assessment of mobility/energy, self-care, and mood/emotion. The change from baseline in ASQoL at Week 16 was assessed using MMRM. A negative change from baseline indicated an improvement.	Baseline, Week 16
ASAS Partial Remission Rate at Week 16	The ASAS partial remission criteria were defined as a value not above 2 units (on a scale of 10) in each of the 4 main ASAS domains: 1. Patient's Global Assessment of Disease Activity (score ranged from 0 [not active] to 10 [very active]); 2. Back Pain (assessed on a scale of 0 [no pain] to 10 [severe pain]); 3. Function (BASFI) (score ranged from 0 [easy] to 10 [impossible]); 4. Inflammation (mean of BASDAI questions 5 and 6 concerning morning stiffness intensity and duration) (score ranged from 0 [none] to 10 [very severe]). The percentage of participants who achieved ASAS partial remission response at Week 16 was assessed using a logistic regression model. Missing responses were imputed as non-responders. Discontinued participants were considered non-responders.	Baseline, Week 16

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2021
• Primary Completion (Actual): April 3, 2024
• Study Completion (Actual): February 14, 2025

Study Registration Dates

• First Submitted: January 28, 2021
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: AIN457; chronic inflammatory disease; secukinumab; non-radiographic spondyloarthritis; inflammatory back pain,
• Additional Relevant MeSH Terms: Axial Spondyloarthritis; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Spinal Diseases; Spondylarthropathies; Ankylosis; Spondylarthritis; Spondylitis; Non-Radiographic Axial Spondyloarthritis; secukinumab
• Other Study ID Numbers: CAIN457I2301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No