Clinical trial NCT02896127: Study of Efficacy and Safety of Secukinumab in Patients With Ankylosing Spondylitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ankylosing Spondyloarthritis
Keywords: Ankylosing Spondyloarthritis
Axial spondyloarthritis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-09-12
Enrollment: 458
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: The Proportion of Participants Who Achieve an ASAS 20 Response (Assessment of SpondyloArthritis International Society Criteria)
timeFrame: Week 16
Secondary outcomes:
measure: The Proportion of Participants Who Achieve an ASAS40 Response
timeFrame: 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.
measure: Change in hsCRP Over Time
timeFrame: 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.
measure: Percentage of Participants Who Achieve an ASAS 5/6 at Week 16
timeFrame: 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.
measure: Participants With BASDAI Response at 16 Weeks
timeFrame: 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.
measure: Change in Short Form (36) - PCS Responders (Improvement of >= 2.5 Points) at Week 16
timeFrame: 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.
measure: Change in ASQoL Score Over Time
timeFrame: change from baseline to Week 16
measure: The Proportion of Patients Who Achieve an ASAS Partial Remission
timeFrame: Week 16
Other outcomes:
Locations:
city: Hefei
country: China
facility: Novartis Investigative Site
state: Anhui
city: Hefei
country: China
facility: Novartis Investigative Site
state: Anhui
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Xiamen
country: China
facility: Novartis Investigative Site
state: Fujian
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Taiyuan
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Urumqi
country: China
facility: Novartis Investigative Site
state: Xinjiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Bengbu
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanxi Province
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Zhejiang
country: China
facility: Novartis Investigative Site
city: Zhenjiang
country: China
facility: Novartis Investigative Site
city: Bruntal
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Ostrava
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Praha 11
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Praha 2
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Uherske Hradiste
country: Czechia
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Gwangju
country: Korea, Republic of
facility: Novartis Investigative Site
city: Incheon
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Reading
country: United Kingdom
facility: Novartis Investigative Site
state: Berkshire
city: Bradford
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: Bath
country: United Kingdom
facility: Novartis Investigative Site
city: Doncaster
country: United Kingdom
facility: Novartis Investigative Site
city: Hull
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Norwich
country: United Kingdom
facility: Novartis Investigative Site
city: Southampton
country: United Kingdom
facility: Novartis Investigative Site
city: Wigan
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: Huang F, Sun F, Wan WG, Wu LJ, Dong LL, Zhang X, Kim TH, Sengupta R, Senolt 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.