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

Ankylosing Spondyloarthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02896127
• Other study ID #: CAIN457F2308
• Secondary ID: 2015-005021-39
• Status: Completed
• Phase: Phase 3
• Start date: October 18, 2016
• Est. completion date: March 19, 2019

Study information

• Verified date: December 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 458
• Est. completion date: March 19, 2019
• Est. primary completion date: May 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 TNFa 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-TNFa 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

Related Conditions & MeSH terms

• Ankylosing Spondyloarthritis
• Spondylarthritis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

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

Locations

Country	Name	City	State
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Bengbu
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hefei	Anhui
China	Novartis Investigative Site	Hefei	Anhui
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanxi Province
China	Novartis Investigative Site	Taiyuan	Shanxi
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Urumqi	Xinjiang
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Xiamen	Fujian
China	Novartis Investigative Site	Zhejiang
China	Novartis Investigative Site	Zhenjiang
Czechia	Novartis Investigative Site	Bruntal	Czech Republic
Czechia	Novartis Investigative Site	Ostrava	Czech Republic
Czechia	Novartis Investigative Site	Praha 11	Czech Republic
Czechia	Novartis Investigative Site	Praha 2	Czech Republic
Czechia	Novartis Investigative Site	Uherske Hradiste
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Gwangju
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
United Kingdom	Novartis Investigative Site	Bath
United Kingdom	Novartis Investigative Site	Bradford	West Yorkshire
United Kingdom	Novartis Investigative Site	Doncaster
United Kingdom	Novartis Investigative Site	Hull
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Norwich
United Kingdom	Novartis Investigative Site	Reading	Berkshire
United Kingdom	Novartis Investigative Site	Southampton
United Kingdom	Novartis Investigative Site	Wigan

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

China,  Czechia,  Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Proportion of Participants Who Achieve an ASAS 20 Response (Assessment of SpondyloArthritis International Society Criteria)	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	Week 16
Secondary	The Proportion of Participants Who Achieve an ASAS40 Response	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.	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.
Secondary	Change in hsCRP Over Time	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.	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.
Secondary	Percentage of Participants Who Achieve an ASAS 5/6 at Week 16	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.	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.
Secondary	Participants With BASDAI Response at 16 Weeks	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.	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.
Secondary	Change in Short Form (36) - PCS Responders (Improvement of >= 2.5 Points) at Week 16	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.	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.
Secondary	Change in ASQoL Score Over Time	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).	change from baseline to Week 16
Secondary	The Proportion of Patients Who Achieve an ASAS Partial Remission	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.	Week 16