24 Week Efficacy and 3-year Safety and Efficacy of Secukinumab in Active Psoriatic Arthritis

Psoriatic Arthritis Clinical Trial

Official title:

A Phase III, Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab in Autoinjectors, to Demonstrate Efficacy at 24 Weeks and to Assess the Long Term Safety, Tolerability and Efficacy up to 3 Years in Subjects With Active Psoriatic Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01989468
• Other study ID #: CAIN457F2318
• Secondary ID: 2013-004002-25
• Status: Completed
• Phase: Phase 3
• Start date: April 10, 2014
• Est. completion date: March 28, 2018

Study information

• Verified date: April 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to provide 24 - 52 week efficacy, safety and tolerability data, and up to 3-year efficacy, safety and tolerability data in subjects with active Psoriatic Arthritis despite current or previous nonsteroidal anti-inflammatory drug (NSAID), disease-modifying antirheumatic drug (DMARD) therapy and/or previous anti-tumor necrosis factor alpha (TNFα) therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 414
• Est. completion date: March 28, 2018
• Est. primary completion date: May 27, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of Psoriatic Arthritis (PsA) classified by ClASsification criteria for Psoriatic ARthritis (CASPAR) criteria.

• Rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies negative.

• Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis.

• Inadequate control of symptoms with NSAID.

Exclusion Criteria:

• Chest X-ray or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process.

• Subjects taking high potency opioid analgesics.

• Previous exposure to secukinumab or other biologic drug directly targeting interleukin-17 (IL-17) or IL-17 receptor.

• Ongoing use of prohibited psoriasis treatments / medications.

• Subjects who have ever received biologic immunomodulating agents except for those targeting TNFa.

• Previous treatment with any cell-depleting therapies.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Biological:
• Secukinumab
Secukinumab 150 mg provided in a 1 mL autoinjector (1 autoinjector for 150 mg dose, 2 autoinjectors for 300 mg dose)
• Placebo
Secukinumab placebo provided in 1 mL autoinjector

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Hobart	Tasmania
Australia	Novartis Investigative Site	Kogarah	New South Wales
Australia	Novartis Investigative Site	Malvern East	Victoria
Australia	Novartis Investigative Site	Maroochydore	Queensland
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Veliko Tarnovo
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Trois Rivieres	Quebec
Canada	Novartis Investigative Site	Victoria	British Columbia
Canada	Novartis Investigative Site	Winnipeg	Manitoba
Czechia	Novartis Investigative Site	Bruntal	Czech Republic
Czechia	Novartis Investigative Site	Praha 2	Czech Republic
Czechia	Novartis Investigative Site	Uherske Hradiste	Czech Republic
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Gommern
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Hildesheim
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Zerbst
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Catania	CT
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Reggio Emilia	RE
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Verona	VR
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Heerlen
Netherlands	Novartis Investigative Site	Rotterdam
Puerto Rico	Novartis Investigative Site	Caguas
Puerto Rico	Novartis Investigative Site	Ponce
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Rostov on Don
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	Sestroretsk
Russian Federation	Novartis Investigative Site	Yaroslavl
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Santander	Cantabria
Spain	Novartis Investigative Site	Sevilla	Andalucia
Switzerland	Novartis Investigative Site	Fribourg
Switzerland	Novartis Investigative Site	St Gallen
United Kingdom	Novartis Investigative Site	Barnsley
United Kingdom	Novartis Investigative Site	Cannock	Staffordshire
United Kingdom	Novartis Investigative Site	Eastbourne
United Kingdom	Novartis Investigative Site	Harrogate
United Kingdom	Novartis Investigative Site	Hull
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London	England
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Salford	Manchester
United Kingdom	Novartis Investigative Site	Stoke on Trent	Staffordshire
United Kingdom	Novartis Investigative Site	Torquay
United Kingdom	Novartis Investigative Site	Tyne And Wear
United States	Novartis Investigative Site	Albany	New York
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Aventura	Florida
United States	Novartis Investigative Site	Bowling Green	Kentucky
United States	Novartis Investigative Site	Duncansville	Pennsylvania
United States	Novartis Investigative Site	Freehold	New Jersey
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Mesquite	Texas
United States	Novartis Investigative Site	Palm Harbor	Florida
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	Sarasota	Florida
United States	Novartis Investigative Site	Wenatchee	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  Germany,  Italy,  Netherlands,  Puerto Rico,  Russian Federation,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients Achieving American College of Rheumatology 20 (ACR20) Response Criteria on Secukinumab Versus Placebo at Week 24	A patient will be considered as improved according the ACR20 criteria if she/he has at least 20% decrease in the swollen and tender joint count, and at least 20% improvements in 3 of the following 5 criteria: physical disability on the Health Assessment Questionnaire; pain score on a visual analog scale; patient global assessment; physician global assessment; and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]	Week 24
Secondary	Proportion of Patients Achieving American College of Rheumatology 50 (ACR50) Response Criteria on Secukinumab Versus Placebo at Week 24	A patient will be considered as improved according the ACR50 criteria if she/he has at least 50% decreases in the swollen and tender joint count, and at least 50% improvements in 3 of the following 5 criteria: physical disability on the Health Assessment Questionnaire; pain score on a visual analog scale; patient global assessment; physician global assessment; and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]	Week 24
Secondary	Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing hsCRP) in Subjects Treated With Secukinumab Versus Placebo at Week 24	DAS28-CRP is a measure of disease activity based on 28-Swollen and Tender Joint Count [proximal interphalangeal joints (10 joints) metacarpophalangeal joints (10) wrists (2) elbows (2) shoulders (2) knees (2)], CRP, and the Patient's Global Assessment of disease activity. Values range from 2.0 to 10.0 where higher values mean a higher disease activity. DAS28-CRP < 2.6 is interpreted as remission.	Week 24
Secondary	Proportion of Subjects Achieving a Psoriatic Area and Severity Index 75 (PASI75) Response in Subjects on Secukinumab Versus Placebo at Week 24	PASI takes into account the extent of the disease, as well as the severity of erythema, scaling, and thickness in different body areas affected by psoriasis. A PASI75 represents an improvement in the PASI score of at least 75% as compared with baseline.	Week 24
Secondary	Change From Baseline in Physical Function Component of the Short-form Health Survey (SF-36-PCS) in Subjects Treated With Secukinumab Versus Placebo at Week 24	SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS is used to assess improvement from baseline of at least one dose of secukinumab versus placebo. The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.	Week 24
Secondary	Percentage of Subjects Achieving a Psoriatic Area and Severity Index 90 (PASI90) Response in Subjects Treated With Secukinumab Versus Placebo at Week 24	PASI takes into account the extent of the disease, as well as the severity of erythema, scaling, and thickness in different body areas affected by psoriasis. A PASI90 represents an improvement in the PASI score of at least 90% as compared with baseline.	Week 24
Secondary	Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI Score) in Subjects Treated With Secukinumab Versus Placebo at Week 24	The HAQ measures physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects and dollar costs. In this trial, only the disability dimension was used. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) and 3 (unable to do). Within each of the 8 categories, only the item indicating the most severe impairment contributes to the category score. The HAQ score is calculated by summing the computed scores for each category and dividing by the number of categories answered. It ranges from 0 (without any difficulty) to 3 (unable to do). A negative change from baseline indicates improvement.	Week 24
Secondary	Proportion of Patients With Dactylitis at Week 24 in the Subset of Patients Who Had Dactylitis at Baseline	The presence of dactylitis was assessed by dactylitis count (number of fingers and toes with dactylitis, with a range of 0-20). If dactylitis is present with any finger or toe, the patient is counted as a patient with dactylitis.	Week 24
Secondary	Proportion of Patients With Enthesitis at Week 24 in the Subset of Patients Who Had Enthesitis at Baseline	The presence of Enthesitis was assessed using a validated enthesitis index that uses 6 sites for evaluation of enthesitis: lateral epicondyle humerus L + R, proximal achilles L + R and medial condyle femur. If enthesitis is present at any of the 6 sites, the subject is counted as a subject with enthesitis.	Week 24
Secondary	Number of Participants With Treatment Emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by Primary System Organ Class (SOC)	Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC).	From first dose of study treatment to last study visit, up to 3 years