Efficacy at 24 Weeks With Long Term Safety, Tolerability and Efficacy up to 5 Years of Secukinumab in Patients of Active Psoriatic Arthritis

Psoriatic Arthritis Clinical Trial

— FUTURE 2  

Official title:

A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab in Prefilled Syringes to Demonstrate the Efficacy at 24 Weeks and to Assess the Long Term Efficacy, Safety and Tolerability up to 5 Years in Patients With Active Psoriatic Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01752634
• Other study ID #: CAIN457F2312
• Secondary ID: 2012-004439-22
• Status: Completed
• Phase: Phase 3
• Start date: April 14, 2013
• Est. completion date: January 9, 2019

Study information

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

Clinical Trial Summary

This study was to provide 24 - 52 week efficacy, safety and tolerability data to support the registration of the secukinumab (AIN457) prefilled syringe (PFS) for subcutaneous self administration in subjects with active PsA despite current or previous NSAID, DMARD and/or anti-TNFα therapy. An additional 4 years of long-term efficacy and safety data were collected during the post Week 52 period of the study.

Description:

At baseline (BSL), subjects whose eligibility was confirmed were randomized to one of the following four treatment groups.

• 75 mg secukinumab

• 150 mg secukinumab

• 300 mg secukinumab

• Placebo At Week 16, all subjects were classified as responders (≥ 20% improvement from BSL in both tender and swollen joint counts) or non-responders.

Subjects who were randomized to a secukinumab treatment group at baseline were targeted to remain on the same dose for the entire trial.

Subjects who were randomized to placebo at baseline were re-randomized at Week 16 as follows:

Placebo non-responders received secukinumab 150 mg s.c. or 300 mg s.c. (1:1) every 4 weeks, starting after the efficacy assessments at Week 16.

Placebo responders continued to receive placebo at Week 16 and Week 20 and received secukinumab 150 mg s.c. or 300 mg s.c. (1:1) every 4 weeks, starting after the efficacy assessments at Week 24.

This was a double-blind, double-dummy, randomized treatment trial until week 52 analysis was completed and open label afterwards.

An amendment to the study protocol (after all patients were in the trial for 2-3 years) introduced changes whereby patients previously treated with secukinumab 75 mg s.c. could change to receive 150 mg s.c. or 300 mg s.c., and patients previously treated with secukinumab 150 mg s.c. could change to receive 300 mg s.c., as deemed appropriate by the investigators.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 397
• Est. completion date: January 9, 2019
• Est. primary completion date: May 12, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:Patients eligible for inclusion in this study have to fulfill all of the following criteria:

• Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at Baseline =3 tender joints out of 78 and =3 swollen out of 76 (dactylitis of a digit counts as one joint each)

• Rheumatoid factor and anti-CCP antibodies negative at screening

• Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or documented history of plaque psoriasis

• Subjects with PsA should have taken NSAIDs for at least 4 weeks prior to randomization with inadequate control of symptoms or at least one dose if stopped due to intolerance to NSAIDs

• Subjects taking corticosteroids must be on a stable dose of =10 mg/day prednisone or equivalent for at least 2 weeks before randomization and should remain on a stable dose up to Week 24

• Subjects taking MTX (= 25 mg/week) are allowed to continue their medication if the dose is stable for at least 4 weeks before randomization and should remain on a stable dose up to Week 52.

Exclusion Criteria:Patients fulfilling any of the following criteria are not eligible for inclusion in this study:

• Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician

• Subjects taking high potency opioid analgesics (e.g. methadone, hydromorphone, morphine)

• Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor

• Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, UV therapy) at randomization. The following wash out periods need to be observed:

• Oral or topical retinoids 4 weeks

• Photochemotherapy (e.g. PUVA) 4 weeks

• Phototherapy (UVA or UVB) 2 weeks

• Topical skin treatments (except in face, scalp and genital area during screening, only corticosteroids with mild to moderate potency) 2 weeks

• Subjects who have ever received biologic immunomodulating agents except for those targeting TNFa, investigational or approved

• Previous treatment with any cell-depleting therapies including but not limited to anti-CD20, investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Drug:
• Secukinumab (AIN457)
Secukinumab (AIN457)
• Placebo
Placebo PFS for s.c. administration.

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
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Hasselt
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Pointe-Claire	Quebec
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Sainte-Foy	Quebec
Canada	Novartis Investigative Site	Trois-Rivieres	Quebec
Canada	Novartis Investigative Site	Waterloo	Ontario
Canada	Novartis Investigative Site	Winnipeg	Manitoba
Czechia	Novartis Investigative Site	Bruntal	Czech Republic
Czechia	Novartis Investigative Site	Pardubice	Czech Republic
Czechia	Novartis Investigative Site	Prague 2
Czechia	Novartis Investigative Site	Uherske Hradiste
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Germering
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Wuerzburg
Germany	Novartis Investigative Site	Zerbst
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Puerto Rico	Novartis Investigative Site	Ponce
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Petrozavodsk
Russian Federation	Novartis Investigative Site	Rostov on Don
Russian Federation	Novartis Investigative Site	Sestroretsk
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	Yaroslavl
Thailand	Novartis Investigative Site	Bangkok
United Kingdom	Novartis Investigative Site	Blackpool
United Kingdom	Novartis Investigative Site	Cambridge
United Kingdom	Novartis Investigative Site	Cannock	Staffordshire
United Kingdom	Novartis Investigative Site	Dudley	West Midlands
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Guildford	Surrey
United Kingdom	Novartis Investigative Site	Leeds	West Yorkshire
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London	England
United Kingdom	Novartis Investigative Site	Salford	Manchester
United Kingdom	Novartis Investigative Site	Southampton
United States	Novartis Investigative Site	Asheville	North Carolina
United States	Novartis Investigative Site	Aventura	Florida
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Columbia	South Carolina
United States	Novartis Investigative Site	Duncansville	Pennsylvania
United States	Novartis Investigative Site	Freehold	New Jersey
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	League City	Texas
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Mesquite	Texas
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Palm Harbor	Florida
United States	Novartis Investigative Site	Peoria	Arizona
United States	Novartis Investigative Site	Sarasota	Florida
United States	Novartis Investigative Site	Syracuse	New York
United States	Novartis Investigative Site	Tamarac	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Germany,  Poland,  Puerto Rico,  Russian Federation,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Achieving American College of Rheumatology 20 (ACR20) Response Criteria	ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).; For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their ACR20 was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.	Week 24
Secondary	Number of Participants Achieving a PASI75 Response in the Subgroup of Subjects Who Have =3% Skin Involvement With Psoriasis	PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area * area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 75 response was defined as participants achieving >= 75% improvement from baseline. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their value was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias.	Week 24
Secondary	Number of Participants Achieving a PASI90 Response in the Subgroup of Subjects Who Have =3% Skin Involvement With Psoriasis	PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area * area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 90 response was defined as participants achieving >= 90% improvement from baseline. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their value was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias.	Week 24
Secondary	Change From Baseline in DAS28-CRP	The DAS28 is a measure of disease activity based on Swollen and Tender Joint Counts, ESR or CRP and the Patient Global Assessment. A DAS28 score > 5.1 implies active disease, = 3.2 low disease activity, and < 2.6 remission. The score can range from 0 - 9.4. The data collected after the patient switched to secukinumab were treated as missing for placebo patients and were analyzed using a mixed-effects repeated measures model. For secukinumab patients, the actual values were used in the analysis.; The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.	Baseline, Week 24
Secondary	Change From Baseline in SF36-Physical Component Score	The SF-36 is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions.; Score range is from 0 (no problems) to 100 (unable to perform the activity). 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 was used.; The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.	Baseline, Week 24
Secondary	Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)	The HAQ-DI assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.	Baseline, Week 24
Secondary	Number of Participants Achieving American College of Rheumatology 50 (ACR50) Response Criteria	ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 50% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their ACR20 was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.	Week 24
Secondary	Number of Participants With Dactylitis in the Subset of Subjects Who Had Dactylitis at Baseline	Resolution of dactylitis was evaluated in the subset of patients who had disease activity at baseline. In this analysis, a lower percentage is desirable and resolution is defined as complete absence of the symptom. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their assessment was set to nonresponse at Week 24 (presence of dactylitis). This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.	Week 24
Secondary	Number of Participants With Enthesitis in the Subset of Subjects Who Had Enthesitis at Baseline	Resolution of enthesitis was evaluated in the subset of patients who had disease activity at baseline. In this analysis, a lower percentage is desirable and resolution is defined as complete absence of the symptom. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their assessment was set to nonresponse at Week 24 (presence of enthesitis). This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.	Week 24