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

Phase 3

Completed

Conditions: Ankylosing Spondyloarthritis

Interventions: Drug: Placebo
Drug: Secukinumab

Registration Number: NCT02896127

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 458

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo s.c.
Secukinumab	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

Primary Outcome Measures

Name	Time	Method
The Proportion of Participants Who Achieve an ASAS 20 Response (Assessment of SpondyloArthritis International Society Criteria)	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

Name	Time	Method
Percentage of Participants Who Achieve an ASAS 5/6 at Week 16	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.
Participants With BASDAI Response at 16 Weeks	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.
The Proportion of Patients Who Achieve an ASAS Partial Remission	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.
The Proportion of Participants Who Achieve an ASAS40 Response	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.
Change in ASQoL Score Over Time	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).
Change in hsCRP Over Time	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.
Change in Short Form (36) - PCS Responders (Improvement of >= 2.5 Points) at 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 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.