Study to Demonstrate the Efficacy (Including Inhibition of Structural Damage), Safety and Tolerability up to 2 Years of Secukinumab in Active Psoriatic Arthritis

Psoriatic Arthritis Clinical Trial

— FUTURE5  

Official title:

A Phase III, Randomized, Double-blind, Placebo Controlled Multi-center Study of Subcutaneous Secukinumab (150 mg and 300 mg) in Prefilled Syringe to Demonstrate Efficacy (Including Inhibition of Structural Damage), Safety, and Tolerability up to 2 Years in Subjects With Active Psoriatic Arthritis (FUTURE 5)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02404350
• Other study ID #: CAIN457F2342
• Secondary ID: 2015-000050-3802
• Status: Completed
• Phase: Phase 3
• Start date: August 31, 2015
• Est. completion date: January 24, 2019

Study information

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

Clinical Trial Summary

The purpose of this study was to demonstrate efficacy including effect on inhibition of progression of structural damage, safety and tolerability up to 2 years with primary focus at Week 16 (week 24 for structural damage), to support the use of secukinumab pre-filled syringe (PFS) by subcutaneous (s.c.) self-administration with or without loading regimen in subjects with active Psoriatic Arthritis (PsA) despite current or previous NSAID, DMARD therapy and/or previous anti-TNFα therapy. Long term efficacy up to 2 years was based on signs and symptoms of joint/bone structure preservation (X-ray) and improvement in physical function measured by Health Assessment Questionnaire - Disability Index (HAQ-DI©), as well as skin and nail improvement for psoriasis signs.

Description:

This multicenter study uses a randomized, double-blind, placebo-controlled, parallel-group design. A screening period (SCR) running up to 10 weeks before randomization will be used to assess subject eligibility followed by 104 weeks of treatment.

At BSL approximately 990 subjects whose eligibility is confirmed will be randomized to one of four treatment groups in 2:2:2:3 ratio:

• Group 1 - secukinumab 150 mg s.c. without loading regimen

• Group 2 - secukinumab 150 mg s.c. with loading dose regimen

• Group 3 - secukinumab 300 mg s.c. with loading dose regimen

• Group 4 - Placebo s.c. NOTE: Group 4 is split into 2 treatment arms, detailed description below. At randomization, subjects will be stratified on the basis of previous anti-TNF therapy as TNFα inhibitor naïve (TNF-naïve) or TNFα inhibitor inadequate responders (TNF-IR).

At each study treatment visit, one (for secukinumab 150 mg) or two (for secukinumab 300 mg) s.c. injections in the form of PFS will be administered, since secukinumab is available in 1.0 mL (150 mg) PFSs. Placebo to secukinumab is also available in 1.0 mL to match the active drug.

At Week 16, subjects who have been randomized to secukinumab groups at BSL (Groups 1-3) will be classified as either responders (≥20% improvement from BSL in both tender joint count (TJC) and swollen joint counts (SJC)) or non-responders (<20% improvement from BSL TJC or SJC), however they will continue on the same treatment irrespective of their response status.

At Week 16, subjects who have been randomized to placebo at BSL (Group 4) will be classified as either responders (≥20% improvement from BSL in both TJC and SJC) or non-responders (<20% improvement from BSL TJC or SJC):

• Subjects who are non-responders will receive either secukinumab 150 mg or 300 mg s.c. every 4 weeks starting at Week 16 (as dictated by treatment sequence assigned to these subjects at BSL).

• Subjects who are responders will continue to receive placebo every 4 weeks. Starting Week 24, these subjects will receive either secukinumab 150 mg s.c. or 300 mg s.c. every 4 weeks starting at Week 24 (as dictated by treatment sequence assigned to these subjects at BSL).

At Week 24, the assessments to address the primary objective will be performed. As described above, subjects who are still receiving placebo s.c. injection will receive either secukinumab 150 mg s.c. or 300 mg s.c. every 4 weeks starting at Week 24 (as dictated by treatment sequence assigned to these subjects at BSL).

At week 52, based on Investigator's decision, the subjects on a 150 mg dose whose signs and symptoms do not show satisfactory response have the possibility to be allocated to secukinumab 300 mg s.c.

After the Week 52 database lock and analyses have been completed, site personnel and subjects will be unblinded to the original randomized treatment (sequence) assignment at randomization. In addition, treatment will be given open-label in order to eliminate the placebo injection. The subject will continue to receive the same active dose of secukinumab as open-label treatment administered until Week 100.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 997
• Est. completion date: January 24, 2019
• Est. primary completion date: August 16, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion 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 BSL =3 tender joints out of 78 and =3 swollen joints out of 76 (dactylitis of a digit counts as one joint each).

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

• Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or a 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 who are regularly taking NSAIDs as part of their PsA therapy are required to be on a stable dose for at least 2 weeks before study randomization and should remain on a stable dose up to Week 24.

• 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.

• Subjects on MTX must be on folic acid supplementation at randomization.

• Subjects who are on a DMARD other than MTX must discontinue the DMARD 4 weeks prior to randomization visit except for leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine wash-out has been performed.

• Subjects who have been on a TNFa inhibitor must have experienced an inadequate response to previous or current treatment with a TNFa inhibitor given at an approved dose for at least 3 months or have stopped treatment due to safety/tolerability problems after at least one administration of a TNFa inhibitor.

• Subjects who have previously been treated with TNFa inhibitors (investigational or approved) will be allowed entry into study after appropriate wash-out period prior to randomization

Exclusion Criteria:

Chest X-ray or chest 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 IL-17 or IL-17 receptor. - Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, UV therapy) at randomization.

• Any intramuscular or intravenous or intra-articular corticosteroid treatment within 4 weeks before randomization.

• 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

• Other protocol-defined exclusion criteria do apply

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Biological:
• Secukinumab
Anti IL-17a monoclonal antibody

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	Tucuman
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Vienna
Canada	Novartis Investigative Site	Sainte-Foy	Quebec
Canada	Novartis Investigative Site	St. John's	Newfoundland and Labrador
Canada	Novartis Investigative Site	Trois-Rivieres	Quebec
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Victoria	British Columbia
Canada	Novartis Investigative Site	Winnipeg	Manitoba
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Vitacura	Santiago
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	Praha 4	Czech Republic
Czechia	Novartis Investigative Site	Praha 4	Czech Republic
Czechia	Novartis Investigative Site	Uherske Hradiste
Denmark	Novartis Investigative Site	Odense
Estonia	Novartis Investigative Site	Tartu
Finland	Novartis Investigative Site	Hyvinkaa
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Bad Abbach
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Germering
Germany	Novartis Investigative Site	Gommern
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Lubeck
Germany	Novartis Investigative Site	Nienburg
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Patras
Greece	Novartis Investigative Site	Thessaloniki	GR
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Eger
Hungary	Novartis Investigative Site	Kistarcsa
Hungary	Novartis Investigative Site	Szekesfehervar
Hungary	Novartis Investigative Site	Veszprem
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Mumbai	Maharashtra
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Secunderabad	Andhra Pradesh
Ireland	Novartis Investigative Site	Dublin 4
Israel	Novartis Investigative Site	Ashkelon
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Palermo	PA
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Potenza	PZ
Italy	Novartis Investigative Site	Udine	UD
Latvia	Novartis Investigative Site	Liepaja
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga	LV
Latvia	Novartis Investigative Site	Valmiera
Lithuania	Novartis Investigative Site	Kaunas	LT
Lithuania	Novartis Investigative Site	Kaunas	LT
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Siauliai
Lithuania	Novartis Investigative Site	Vilnius
Lithuania	Novartis Investigative Site	Vilnius
Mexico	Novartis Investigative Site	Merida	Yucatan
Mexico	Novartis Investigative Site	Metepec	Estado De Mexico
Mexico	Novartis Investigative Site	Mexicali	Baja California
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Mexico	Novartis Investigative Site	San Luis Potosi
Netherlands	Novartis Investigative Site	Maastricht
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Schiedam
Netherlands	Novartis Investigative Site	Utrecht
Philippines	Novartis Investigative Site	Manila	Metro Manila
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Quezon City
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Kemerovo
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Nizhniy Novgorod
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Orenburg
Russian Federation	Novartis Investigative Site	Rostov on Don
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	Smolensk
Russian Federation	Novartis Investigative Site	St-Petersburg
Russian Federation	Novartis Investigative Site	Yaroslavl
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Baracaldo	Vizcaya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Bilbao	Pais Vasco
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sabadell	Barcelona
Spain	Novartis Investigative Site	Sant Joan Despi	Barcelona
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Vigo	Pontevedra
Sweden	Novartis Investigative Site	Stockholm
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkoknoi	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Khon Kaen	THA
Thailand	Novartis Investigative Site	Songkhla	Hat Yai
United Kingdom	Novartis Investigative Site	Basingstoke	Hampshire
United Kingdom	Novartis Investigative Site	Bath
United Kingdom	Novartis Investigative Site	Bradford	West Yorkshire
United Kingdom	Novartis Investigative Site	Christchurch	Dorset
United Kingdom	Novartis Investigative Site	Dundee
United Kingdom	Novartis Investigative Site	Eastbourne
United Kingdom	Novartis Investigative Site	Edinburgh
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Inverness	Invernesshire
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	London
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	Oxford
United Kingdom	Novartis Investigative Site	Portsmouth
United Kingdom	Novartis Investigative Site	Salford	Manchester
United Kingdom	Novartis Investigative Site	Stoke on Trent	Staffordshire
United Kingdom	Novartis Investigative Site	Truro	Cornwall
United Kingdom	Novartis Investigative Site	Wigan
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Brandon	Florida
United States	Novartis Investigative Site	Brooklyn	New York
United States	Novartis Investigative Site	Coeur d'Alene	Idaho
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Duncansville	Pennsylvania
United States	Novartis Investigative Site	Jackson	Tennessee
United States	Novartis Investigative Site	Kingsport	Tennessee
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	Portland	Oregon
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Shreveport	Louisiana
United States	Novartis Investigative Site	Spokane	Washington
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Upland	California
United States	Novartis Investigative Site	Wexford	Pennsylvania
United States	Novartis Investigative Site	Wyomissing	Pennsylvania
Vietnam	Novartis Investigative Site	Hanoi
Vietnam	Novartis Investigative Site	Ho Chi Minh
Vietnam	Novartis Investigative Site	Ho Chi Minh	VNM

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Austria,  Canada,  Chile,  Czechia,  Denmark,  Estonia,  Finland,  Germany,  Greece,  Guatemala,  Hungary,  India,  Ireland,  Israel,  Italy,  Latvia,  Lithuania,  Mexico,  Netherlands,  Philippines,  Russian Federation,  Spain,  Sweden,  Thailand,  United Kingdom, 

References & Publications (1)

Mease P, van der Heijde D, Landewé R, Mpofu S, Rahman P, Tahir H, Singhal A, Boettcher E, Navarra S, Meiser K, Readie A, Pricop L, Abrams K. Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results fr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Active Psoriatic Arthritis (PsA) Achieving an American College of Rheumatology Response 20 (ACR20) at Week 16	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 based on tender 78-joint count, swollen 76-joint count and at least 20% improvement in 3 of the following 5 measures: participant's assessment of PsA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, participant's self-assessed disability (Health Assessment Questionnaire Disability Index (HAQ-DI) score), and acute phase reactant evaluated as (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR)).	Week 16
Secondary	Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS))	PsA modified vdH-mTSS scoring method was used to assess bone erosion & joint space narrowing (JSN) in hands & feet; that included the 2nd through 5th distal interphalangeal (DIP) joints of each hand. Maximum score for erosions was 5 in joints of the hands and 10 in joints of the feet with 0=no erosions, 1=discrete erosion, 2=large erosion not passing the mid-line, and 3=large erosion passing the mid-line. JSN is: 0=normal, 1=asymmetrical or minimal narrowing up to a maximum of 25%, 2 = definite narrowing with loss of up to 50% of the normal space, 3 = definite narrowing with loss of 50-99% of the normal space, and 4 = absence of a joint space. Maximum erosion score is 320 (200 for the hands and 120 for the feet), and the max total JSN score is 208 (160 for the hands and 48 for the feet). Total radiographic score (hands & feet combined) ranges from 0 to 528, where higher scores indicate more articular damage	Baseline, Week 24
Secondary	Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 75 (PASI75) Response	The efficacy of secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen) at Week 16 compared with placebo based on the proportion of patients achieving Psoriatic Area and Severity Index 75 (PASI75) response.	Week 16
Secondary	Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 90 (PASI90) Response	The efficacy of secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen) at Week 16 compared with placebo based on the proportion of patients achieving Psoriatic Area and Severity Index 90 (PASI90) response.	16 weeks
Secondary	Count and Percentage of Patients Achieving an ACR50 Response	ACR 50 Response is a measure based on American College of Rheumatology criteria of at least a 50% improvement in the number of tender and swollen joints, and a 50% improvement in at least 3 of the following: the patient's global assessment of disease status; the patient's assessment of pain; the patient's assessment of function measured using the Stanford Health Assessment Questionnaire the physician's global assessment of disease status; serum C-reactive protein levels.	16 weeks
Secondary	Change From Baseline in HAQ-DI© Score	The change (within treatment) on secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen), at Week 16 compared with placebo for the disease activity assessed by the changes in The Health Assessment Questionnaire disability index (HAQ-DI) relative to baseline.	16 weeks
Secondary	Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing High Sensitivity C-Reactive Protein (hsCRP))	The improvement on secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen) at Week 16 compared with placebo for the disease activity assessed by the changes in Disease Activity Score for 28 joints (DAS28-CRP) (utilizing High sensitivity C-Reactive Protein (hsCRP)) relative to baseline.; Scores range from 0 (no difficulty) to 3 (unable to do)	16 weeks
Secondary	Count and Percentage of Patients With Enthesitis in the Subset of Patients Who Had Enthesitis at Baseline	The efficacy of secukinumab pooled regimen (150 mg with or without loading regimen, and 300 mg with loading regimen) at Week 16 compared with placebo based on the proportion of patients with enthesitis in the subset of patients who had enthesitis at baseline	16 weeks
Secondary	Count and Percentage of Participants With Dactylitis in the Subset of Patients Who Have Dactylitis at Baseline	The efficacy of secukinumab pooled regimen (150 mg with or without loading regimen, and 300 mg with loading regimen) at Week 16 compared with placebo based on the proportion of patients with dactylitis in the subset of patients who have dactylitis at baseline	16 weeks