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

• 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: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Locations

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

• 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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Merola JF, McInnes IB, Deodhar AA, Dey AK, Adamstein NH, Quebe-Fehling E, Aassi M, Peine M, Mehta NN. Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications. Rheumatol Ther. 2022 Jun;9(3):935-955. doi: 10.1007/s40744-022-00434-z. Epub 2022 Mar 19.

van der Horst-Bruinsma I, Miceli-Richard C, Braun J, Marzo-Ortega H, Pavelka K, Kivitz AJ, Deodhar A, Bao W, Porter B, Pournara E. A Pooled Analysis Reporting the Efficacy and Safety of Secukinumab in Male and Female Patients with Ankylosing Spondylitis. Rheumatol Ther. 2021 Dec;8(4):1775-1787. doi: 10.1007/s40744-021-00380-2. Epub 2021 Oct 7.

Huang F, Sun F, Wan WG, Wu LJ, Dong LL, Zhang X, Kim TH, Sengupta R, Šenolt L, Wang Y, Qiu HM, Porter B, Haemmerle S. Secukinumab provided significant and sustained improvement in the signs and symptoms of ankylosing spondylitis: results from the 52-week, Phase III China-centric study, MEASURE 5. Chin Med J (Engl). 2020 Nov 5;133(21):2521-2531. doi: 10.1097/CM9.0000000000001099.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02896127
• Other Study ID Numbers: CAIN457F2308; 2015-005021-39 ( EudraCT Number )
• First Posted: September 12, 2016
• 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

• 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:

Spondylitis; Spondylitis, Ankylosing; Spondylarthritis; Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Spinal Diseases; Spondylarthropathies; Ankylosis; Joint Diseases; Arthritis