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Study of Efficacy and Safety of Secukinumab in Patients With Ankylosing Spondylitis

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ClinicalTrials.gov Identifier: NCT02896127
Recruitment Status : Completed
First Posted : September 12, 2016
Results First Posted : December 30, 2020
Last Update Posted : December 30, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this trial is to demonstrate the clinical efficacy at week 16; and to demonstrate safety and tolerability of secukinumab compared to placebo in patients with ankylosing spondylitis at week 16 and long term safety up to Week 52.

Condition or disease Intervention/treatment Phase
Ankylosing Spondyloarthritis Drug: Secukinumab Drug: Placebo Phase 3

Detailed Description:

This multicenter 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 eligibility, followed by 52 weeks of treatment.

At baseline, subjects were randomized to one of the two treatment groups:

  • Group 1: 300 subjects, secukinumab 150 mg (1 mL, 150 mg/mL) s.c. pre-filled syringes (PFS) at BSL, Weeks 1, 2, and 3, followed by administration every four weeks starting at Week 4
  • Group 2: 150 subjects, placebo (1 mL) s.c. PFS at BSL, Weeks 1, 2, 3, 4, 8, and 12, followed by secukinumab 150 mg (1 mL, 150 mg/mL) administration every four weeks starting at Week 16

The subjects were stratified at randomization according to the region (China and non-China). Approximately 70% of randomized subjects were from China (327 Chinese subjects) in order to evaluate the efficacy and safety in this subject population. No more than 30% TNFα inhibitor inadequate responders (TNF-IR) subjects were to be enrolled in the study.

Starting at Week 16, all subjects switched to open-label secukinumab 150 mg, including all placebo subjects; however, all subjects and investigators/site staff remained blinded to the original randomized treatment group assignment (150 mg vs placebo). Study treatment continued up to Week 48.

An end of treatment visit was done 4 weeks after last study treatment administration and a post treatment follow-up visit was done 12 weeks after last study treatment administration for all subjects (regardless of whether they completed the entire study as planned or discontinued prematurely).

Subjects were instructed in detail how to self-administer the s.c. injection using PFS. Each injection was administered into an appropriate injection site of the body (thighs, arms, or abdomen). All injections were performed at the study site. Site personnel administered the injections to subjects who were not able to, or felt insecure to self-administer. Rescue medication was not allowed until Week 20. However, subjects who were deemed by the investigator not to be benefiting from the study treatment based on safety and efficacy assessments or for any reason of their own accord were free to discontinue participation in the study at any time.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 458 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-blind, Placebo-controlled, Phase III Multicenter Study of Subcutaneous Secukinumab to Compare Efficacy at 16 Weeks With Placebo and Assess Safety and Tolerability up to 52 Weeks in Subjects With Active Ankylosing Spondylitis
Actual Study Start Date : October 18, 2016
Actual Primary Completion Date : May 14, 2018
Actual Study Completion Date : March 19, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Secukinumab

Arm Intervention/treatment
Experimental: Secukinumab

Secukinumab 150 mg s.c.

Arm includes all patients who received at least 1 dose of study drug including placebo switchers at Week 16

Drug: Secukinumab

Induction: 4x 150 mg Secukinumab s.c. weekly

Maintenance: 150 mg Secukinumab s.c. monthly

All Subjects received blinded treatment weekly starting at baseline, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until Week 16. At Week 16, Group 1 patients continued using secukinumab 150 mg and Group 2 patients started receiving secukinumab 150 mg dosing every four weeks. Treatment was provided open-label from Week 16 onward, as all patients took 150 mg s.c. every 4 weeks; however, subjects, investigators, and site staff remained blinded to initial randomized group assignment.

Other Name: AIN457

Placebo Comparator: Placebo
Placebo s.c.
Drug: Placebo
Induction: 4x placebo s.c. weekly Maintenance: placebo s.c. monthly




Primary Outcome Measures :
  1. The Proportion of Participants Who Achieve an ASAS 20 Response (Assessment of SpondyloArthritis International Society Criteria) [ Time Frame: Week 16 ]
    ASAS20 response is defined as an improvement of ≥20% and ≥1 units on a scale of 10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 10 in the remaining domain


Secondary Outcome Measures :
  1. The Proportion of Participants Who Achieve an ASAS40 Response [ Time Frame: The secondary outcome analysis occurred only at Week 16. Thus, while data were collected beyond week 16, they were not part of the secondary outcomes. ]

    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

    The number analyzed for some of continuous outcome variables are the number of participants for whom the specific outcome data were available. Thus the number for these variables differs from the FAS.


  2. Change in hsCRP Over Time [ Time Frame: Change from baseline to Week 16. The secondary outcome analysis occurred only at Week 16. Thus, while data were collected beyond week 16, they were not part of the secondary outcomes. ]

    hsCRP is measured as a marker of inflammation from blood samples during the study

    The number analyzed for some of continuous outcome variables are the number of participants for whom the specific outcome data were available. Thus the number for these variables differs from the FAS.


  3. Percentage of Participants Who Achieve an ASAS 5/6 at Week 16 [ Time Frame: Week 16: The secondary outcome analysis occurred only at Week 16. Thus, while data were collected beyond week 16, they were not part of the secondary outcomes. ]

    The ASAS 5/6 improvement criteria is an improvement of ≥20% in at least five of all six domains

    The number analyzed for some of continuous outcome variables are the number of participants for whom the specific outcome data were available. Thus the number for these variables differs from the FAS.


  4. Participants With BASDAI Response at 16 Weeks [ Time Frame: The secondary outcome analysis occurred only at Week 16. Thus, while data were collected beyond week 16, they were not part of the secondary outcomes. ]

    The BASDAI or Bath Ankylosing Spondylitis Disease Activity Index consists of a 0 through 10 scale (0 being no problem and 10 being the worst problem, captured as a continuous VAS), which is used to answer 6 questions pertaining to the 5 major symptoms of AS

    The number analyzed for some of continuous outcome variables are the number of participants for whom the specific outcome data were available. Thus the number for these variables differs from the FAS.


  5. Change in Short Form (36) - PCS Responders (Improvement of >= 2.5 Points) at Week 16 [ Time Frame: The secondary outcome analysis occurred only at Week 16. Thus, while data were collected beyond week 16, they were not part of the secondary outcomes. ]

    The Physical Component Summary (PCS) SF-36 is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions

    The number analyzed for some of continuous outcome variables are the number of participants for whom the specific outcome data were available. Thus the number for these variables differs from the FAS.


  6. Change in ASQoL Score Over Time [ Time Frame: change from baseline to Week 16 ]

    The Ankylosing Spondylitis Quality of Life (ASQoL) is an instrument to assess health-related quality of life among adult patients with Ankylosing Spondylitis.

    Each statement on the ASQoL is given a score of "1" or "0". A score of "1" is given where the item is affirmed, indicating adverse QoL. All item scores are summed to give a total score or index. Scores can range from 0 (good QoL) to 18 (poor QoL).


  7. The Proportion of Patients Who Achieve an ASAS Partial Remission [ Time Frame: Week 16 ]

    The The Assessment in SpondyloArthritis International Society (ASAS) partial remission criteria are defined as a value not above 2 units in each of the four main domains on a scale of 10

    The number analyzed for some of continuous outcome variables are the number of participants for whom the specific outcome data were available. Thus the number for these variables differs from the FAS.




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.


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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-lactating female patients at least 18 years of age

Diagnosis of moderate to severe AS with prior documented radiologic evidence (x-ray or radiologist's report) fulfilling the Modified New York criteria for AS:

  • Active AS assessed by BASDAI ≥4 (0-10) at Baseline
  • Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at Baseline
  • Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at Baseline Patients should have had inadequate response or failure to respond to at least 2 NSAIDs at an approved dose for a minimum of 4 weeks in total and a minimum of 2 weeks for each NSAID prior to randomization, or less than 4 weeks if therapy had to be withdrawn due to intolerance, toxicity or contraindications Patients who are regularly taking NSAIDs (including COX-1 or COX-2 inhibitors) as part of their AS therapy are required to be on a stable dose for at least 2 weeks before randomisation Patients who have been on a TNFα inhibitor (not more than one) must have experienced an inadequate response to previous or current treatment given at an approved dose for at least 3 months prior to randomization or have been intolerant to at least one administration of an anti-TNFα agent

Exclusion Criteria:

  • 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 IL-17 or IL-17 receptor
    • Pregnant or nursing (lactating) women

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): NCT02896127


Locations
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China, Anhui
Novartis Investigative Site
Hefei, Anhui, China, 230001
Novartis Investigative Site
Hefei, Anhui, China, 230022
China, Beijing
Novartis Investigative Site
Beijing, Beijing, China, 100039
Novartis Investigative Site
Beijing, Beijing, China, 100730
China, Fujian
Novartis Investigative Site
Xiamen, Fujian, China, 361001
China, Guangdong
Novartis Investigative Site
Guangzhou, Guangdong, China, 510000
Novartis Investigative Site
Guangzhou, Guangdong, China, 51000
China, Hubei
Novartis Investigative Site
Wuhan, Hubei, China, 430030
China, Hunan
Novartis Investigative Site
Changsha, Hunan, China, 410008
Novartis Investigative Site
Changsha, Hunan, China, 410011
China, Jiangsu
Novartis Investigative Site
Nanjing, Jiangsu, China, 210029
China, Shanxi
Novartis Investigative Site
Taiyuan, Shanxi, China, 030001
China, Sichuan
Novartis Investigative Site
Chengdu, Sichuan, China, 610041
China, Xinjiang
Novartis Investigative Site
Urumqi, Xinjiang, China, 830001
China
Novartis Investigative Site
Beijing, China, 100029
Novartis Investigative Site
Bengbu, China, 233004
Novartis Investigative Site
Shanghai, China, 200040
Novartis Investigative Site
Shanghai, China, 200127
Novartis Investigative Site
Shanghai, China, 200433
Novartis Investigative Site
Shanghai, China
Novartis Investigative Site
Shanxi Province, China
Novartis Investigative Site
Tianjin, China, 300052
Novartis Investigative Site
Zhejiang, China
Novartis Investigative Site
Zhenjiang, China
Czechia
Novartis Investigative Site
Bruntal, Czech Republic, Czechia, 792 01
Novartis Investigative Site
Ostrava, Czech Republic, Czechia, 772 00
Novartis Investigative Site
Praha 11, Czech Republic, Czechia, 148 00
Novartis Investigative Site
Praha 2, Czech Republic, Czechia, 128 50
Novartis Investigative Site
Uherske Hradiste, Czechia, 686 01
Korea, Republic of
Novartis Investigative Site
Seoul, Seocho Gu, Korea, Republic of, 06591
Novartis Investigative Site
Busan, Korea, Republic of, 602739
Novartis Investigative Site
Gwangju, Korea, Republic of, 61469
Novartis Investigative Site
Incheon, Korea, Republic of, 405 760
Novartis Investigative Site
Seoul, Korea, Republic of, 03080
Novartis Investigative Site
Seoul, Korea, Republic of, 04763
United Kingdom
Novartis Investigative Site
Reading, Berkshire, United Kingdom, RG1 5AN
Novartis Investigative Site
Bradford, West Yorkshire, United Kingdom, BD9 6RJ
Novartis Investigative Site
Bath, United Kingdom, BA1 1RL
Novartis Investigative Site
Doncaster, United Kingdom, DN2 5LT
Novartis Investigative Site
Hull, United Kingdom, HU16 5JQ
Novartis Investigative Site
London, United Kingdom, NW1
Novartis Investigative Site
Norwich, United Kingdom, NR1 3SR
Novartis Investigative Site
Southampton, United Kingdom, SO16 6YD
Novartis Investigative Site
Wigan, United Kingdom, WN6 9EP
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] January 15, 2018
Statistical Analysis Plan  [PDF] August 16, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02896127    
Other Study ID Numbers: CAIN457F2308
2015-005021-39 ( EudraCT Number )
First Posted: September 12, 2016    Key Record Dates
Results First Posted: December 30, 2020
Last Update Posted: December 30, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Ankylosing Spondyloarthritis
Axial spondyloarthritis
Additional relevant MeSH terms:
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Spondylitis
Spondylitis, Ankylosing
Spondylarthritis
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Ankylosis
Joint Diseases
Arthritis