Study of Efficacy and Safety of Secukinumab in Chinese Subjects With Active PsA Compared to Placebo.

A Phase III Randomized, Double-blind, Placebo Controlled, Multicenter, Bridging Study of Subcutaneous Secukinumab, to Demonstrate Efficacy After Sixteen Weeks of Treatment and to Assess Safety, Tolerability and Long-term Efficacy Follow-up to One Year in Chinese Subjects With Active Psoriatic Arthritis

The purpose of this study was to assess the efficacy and safety of secukinumab in Chinese participants with active Psoriatic arthritis (PsA ) compared to placebo.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Drug: AIN457; Other: Secukinumab Placebo

Detailed Description

This study used a randomized, double-blind, placebo-controlled, parallel-group design.

A screening period running up to 10 weeks before randomization was used to assess participant eligibility followed by 52 weeks of treatment.

A follow-up visit was done 12 weeks after last study treatment administration for all participants, regardless of whether they completed the entire study as planned or discontinued prematurely.

At Baseline, the patients fulfilling the inclusion criteria were randomized to one of the following two groups.

Group 1 : Secukinumab Dose level 1 s.c. at BSL, Week 1, 2, 3, 4, 8, and 12 Group 2 : Secukinumab Placebo s.c. at BSL, Week 1, 2, 3, 4, 8, and 12.

At Week 16, participants in Group 1 and Group 2 were to be re-randomized separately in a 1:1 ratio to receive secukinumab 150 mg or secukinumab 300 mg.

The duration of the entire treatment period was 52 weeks.

The primary objective was to demonstrate the treatment effect of secukinumab in Chinese subjects with active PsA by assessing American College of Rheumatology rresponse 20 (ACR20 response) rates at Week 16.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Jinan, China, 250012
    • Novartis Investigative Site
  • Shanghai, China, 200127
    • Novartis Investigative Site
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • Novartis Investigative Site
  • Guang Dong Province
    • Guang Zhou, Guang Dong Province, China, 510120
      • Novartis Investigative Site
  • Hunan
    • Zhuzhou, Hunan, China, 412000
      • Novartis Investigative Site
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014010
      • Novartis Investigative Site
    • Hohhot, Inner Mongolia, China, 10050
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Novartis Investigative Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Novartis Investigative Site
    • Pingxiang, Jiangxi, China, 337000
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed.
• Chinese male or non-pregnant, non-lactating Chinese female participants at least 18 years of age.
• Diagnosis of PsA classified by Classification of Psoriatic Arthritis (CASPAR) criteria and with symptoms for at least 6 months with moderate to severe Psoriatic arthritis (PsA).
• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies negative at screening.
• Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or a documented history of plaque psoriasis.
• Participants on Methotrexate (MTX) must be on folic acid supplementation at randomization.
• Participants who are on a DMARD other than MTX must discontinue the DMARD 4 weeks prior to randomization visit except for leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine washout has been performed.

Exclusion Criteria:

• Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician
• Participants taking high potency opioid analgesics (e.g., methadone, hydromorphone, morphine).
• Previous exposure to secukinumab or other biologic drug directly targeting interleukin- 17 (IL-17) or IL-17 receptor
• Participants who have ever received biologic immunomodulating agents except for those targeting Tumor necrosis factor alpha (TNFα).
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective contraception during the entire study (during the entire study).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Participants received 150 mg dose (dose level 1) of Secukinumab	Drug: AIN457; Secukinumab 150 mg was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection; Other Names: Secukinumab
Placebo Comparator: Arm 2; Participants received Placebo of the study drug.	Other: Secukinumab Placebo; Secukinumab placebo was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection
Active Comparator: Arm 3; Participants who received Placebo and switched to dose level 1 (150 mg) of secukinumab.	Drug: AIN457; Secukinumab 150 mg was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection; Other Names: Secukinumab; Other: Secukinumab Placebo; Secukinumab placebo was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection
Active Comparator: Arm 4; Participants who received Placebo and switched to dose level 2 (300 mg) of secukinumab.	Drug: AIN457; Secukinumab 150 mg was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection; Other Names: Secukinumab; Other: Secukinumab Placebo; Secukinumab placebo was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR20 Response at Week 16	Assessed the efficacy of secukinumab relative to placebo at week 16 using Non-responder imputation (NRI) and based on the percentage of participants achieving an ACR20 response (ACR = American College of Rheumatology). ACR20 response criteria is response ≥ 20% improvement based on: Swollen Joint Count (SJC)/Tender Joint Count (TJC), Patient's global assessment of disease activity (PaGA) (Visual Analog Scale (VAS)), Physician's global assessment of disease activity (PhGA) (VAS), Patient's assessment of PsA pain intensity (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI), and High-sensitivity C-reactive protein (hsCRP) or Erythrocyte sedimentation rate (ESR).	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR50 Response at Week 16	To assess the effect of secukinumab versus placebo on the composite endpoint ACR50 response and based on the percentage of participants achieving an ACR50 response at Week 16 using NRI. ACR50 response criteria is response ≥ 50% improvement based on: Swollen Joint Count (SJC)/Tender Joint Count (TJC), Patient's global assessment of disease activity (PaGA) (VAS), Physician's global assessment of disease activity (PhGA) (VAS), Patient's assessment of PsA pain intensity (VAS), HAQ-DI, and hsCRP or ESR.	16 weeks
Change From Baseline in DAS28-CRP Scores Using Mixed Model Repeated Scores (MMRM) at Week 16	To assess the effect of secukinumab versus placebo on change from BSL in DAS28-CRP. The assessment is based on the reduction in DAS28-CRP score. The DAS28 is a measure of disease activity based on Swollen and Tender Joint Counts, ESR or CRP and the Patient Global Assessment of Disease Activity. The range of DAS28 score is 0-10. Higher score means more active disease. Negative change from baseline indicates a favorable outcome.	16 weeks
Change From Baseline in PASDAS Scores Using MMRM at Week 16	To assess the the effect of secukinumab versus placebo on change from Baseline in PASDAS. Assessment was based on reduction in PASDAS score. PASDAS is a measure of disease activity based on Patient reported measures (excluding mental component score (MCS) of the medical outcomes survey Short Form-36 (SF-36-PCS)), skin, peripheral joint counts (Tender and Swollen joint counts), Dactylitis (LDI), Enthesitis (LEI), acute phase response (CRP) and Patient & Physician global VAS scores. The range of PASDAS is 0-10. Higher score means more active disease. Negative change from baseline indicates a favorable outcome.	16 weeks
Change From Baseline in SF36-PCS Scores Using MMRM at Week 16	To assess the effect of secukinumab versus placebo on change from Baseline in SF-36 PCS. The SF-36 is a widely used and extensively studied instrument to measure HRQoL among healthy participants and participants with acute and chronic conditions. Two overall summary scores, the Physical Component Score (PCS) and the Mental Component Score (MCS) also can be computed. SF36-PCS was used in this study. The range of SF36-PCS score is 0-100. Higher score means better health status. Negative change from baseline indicates a unfavorable outcome.	16 weeks
Change From Baseline in HAQ-DI Scores Using MMRM at Week 16	To assess the effect of secukinumab versus placebo on change from Baseline in HAQ-DI. Assessment was based on improvement in HAQ-DI PCS scores. The HAQ-DI© is one of the most widely used measures to assess the long-term influence of chronic disease on a participant's level of functional ability and activity restriction, and calculated based on HAQ-DI questionnaire. There are 20 questions in eight categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The range of score is 0-3. Higher score means more severe disability. Negative change from baseline indicates a favorable outcome.	16 weeks

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 novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2021
• Primary Completion (Actual): June 2, 2022
• Study Completion (Actual): March 10, 2023

Study Registration Dates

• First Submitted: January 14, 2021
• First Submitted That Met QC Criteria: January 14, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Estimated): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 7, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: PsA; SpA; AIN457; spondylarthritis; secukinumab; immune-mediated chronic inflammatory disease; inflammatory musculoskeletal disease; China bridging study
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457F2367

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
• product manufactured in and exported from the U.S.: Yes