NCT02404350: FUTURE5

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

Completed Phase 3 Results posted Last updated 20 April 2020

What this trial tests

Phase 3 trial testing Secukinumab in Psoriatic Arthritis in 997 participants. Completed in 24 January 2019.

Timeline

31 August 2015

Primary endpoint
16 August 2017

24 January 2019

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	997
Start date	31 August 2015
Primary completion	16 August 2017
Estimated completion	24 January 2019
Sites	172 locations across Italy, Finland, Ireland, Vietnam, Philippines, Guatemala, Denmark, Netherlands

Drugs / interventions tested

• Secukinumab (secukinumab) — full drug profile →

Conditions studied

• Psoriatic Arthritis — all drugs for Psoriatic Arthritis →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Psoriatic Arthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Active Psoriatic Arthritis (PsA) Achieving an American College of Rheumatology Response 20 (ACR20) at Week 16 Primary · 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

Group	Value	95% CI
Secukinumab 150 mg Without Load	59.5
Secukinumab 150 mg With Load	55.5
Secukinumab 300 mg With Load	62.6
Placebo	27.4

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)) Secondary · Baseline, Week 24

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% o

baseline

Group	Value	95% CI
Secukinumab 150 mg Without Load	15.25	± 37.098
Secukinumab 150 mg With Load	13.50	± 25.636
Secukinumab 300 mg With Load	12.90	± 23.781
Placebo	14.95	± 38.236

change

Group	Value	95% CI
Secukinumab 150 mg Without Load	-0.10	± 2.872
Secukinumab 150 mg With Load	0.13	± 1.222
Secukinumab 300 mg With Load	0.02	± 1.336
Placebo	0.50	± 1.708

Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 75 (PASI75) Response Secondary · Week 16

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.

Group	Value	95% CI
Secukinumab 150 mg Without Load	68
Secukinumab 150 mg With Load	75
Secukinumab 300 mg With Load	77
Placebo	20

Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 90 (PASI90) Response Secondary · 16 weeks

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.

Group	Value	95% CI
Secukinumab 150 mg Without Load	37
Secukinumab 150 mg With Load	46
Secukinumab 300 mg With Load	59
Placebo	15

Count and Percentage of Patients Achieving an ACR50 Response Secondary · 16 weeks

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.

Group	Value	95% CI
Secukinumab 150 mg Without Load	71
Secukinumab 150 mg With Load	79
Secukinumab 300 mg With Load	88
Placebo	27

Change From Baseline in HAQ-DI© Score Secondary · 16 weeks

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.

Group	Value	95% CI
Secukinumab 150 mg Without Load	-0.45	± 0.035
Secukinumab 150 mg With Load	-0.44	± 0.035
Secukinumab 300 mg With Load	-0.55	± 0.035
Placebo	-0.21	± 0.029

Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing High Sensitivity C-Reactive Protein (hsCRP)) Secondary · 16 weeks

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)

Group	Value	95% CI
Secukinumab 150 mg Without Load	-1.29	± 0.074
Secukinumab 150 mg With Load	-1.29	± 0.075
Secukinumab 300 mg With Load	-1.49	± 0.074
Placebo	-0.63	± 0.062

Count and Percentage of Patients With Enthesitis in the Subset of Patients Who Had Enthesitis at Baseline Secondary · 16 weeks

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

Group	Value	95% CI
Secukinumab 150 mg Without Load	75
Secukinumab 150 mg With Load	64
Secukinumab 300 mg With Load	62
Placebo	124

Count and Percentage of Participants With Dactylitis in the Subset of Patients Who Have Dactylitis at Baseline Secondary · 16 weeks

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

Group	Value	95% CI
Secukinumab 150 mg Without Load	45
Secukinumab 150 mg With Load	34
Secukinumab 300 mg With Load	28
Placebo	84

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 24 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 24 weeks. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Secukinumab 150 mg Without Load

Serious: 6/222 (3%)

Deaths: 0/222

Secukinumab 150 mg With Load

Serious: 9/220 (4%)

Deaths: 0/220

Secukinumab 300 mg With Load

Serious: 7/222 (3%)

Deaths: 0/222

Secukinumab Total

Serious: 25/822 (3%)

Deaths: 0/822

Placebo

Serious: 12/332 (4%)

Deaths: 0/332

Serious adverse events (43 terms)

Reaction	System	Secukinumab 150 mg Without…	Secukinumab 150 mg With Load	Secukinumab 300 mg With Load	Secukinumab Total	Placebo
Cellulitis	Infections and infestations	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—	—
Colitis ulcerative	Gastrointestinal disorders	—	—	—	—	—
Crohn's disease	Gastrointestinal disorders	—	—	—	—	—
Diverticulum	Gastrointestinal disorders	—	—	—	—	—
Rectal haemorrhage	Gastrointestinal disorders	—	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—	—
Anaphylactic reaction	Immune system disorders	—	—	—	—	—
Otitis externa	Infections and infestations	—	—	—	—	—
Tonsillitis	Infections and infestations	—	—	—	—	—
Typhoid fever	Infections and infestations	—	—	—	—	—
Viral infection	Infections and infestations	—	—	—	—	—
Ankle fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Concussion	Injury, poisoning and procedural complications	—	—	—	—	—
Foreign body	Injury, poisoning and procedural complications	—	—	—	—	—
Hip fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Humerus fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Road traffic accident	Injury, poisoning and procedural complications	—	—	—	—	—
Tibia fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Ulna fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Computerised tomogram thorax abnormal	Investigations	—	—	—	—	—
Arthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Chondropathy	Musculoskeletal and connective tissue disorders	—	—	—	—	—

Other adverse events (27 terms — click to expand)

Reaction	System	Secukinumab 150 mg Without…	Secukinumab 150 mg With Load	Secukinumab 300 mg With Load	Secukinumab Total	Placebo
Viral upper respiratory tract infection	Infections and infestations	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—
Dyslipidaemia	Metabolism and nutrition disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—
Hypercholesterolaemia	Metabolism and nutrition disorders	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Psoriasis	Skin and subcutaneous tissue disorders	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—
Rhinitis	Infections and infestations	—	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—	—
Hyperlipidaemia	Metabolism and nutrition disorders	—	—	—	—	—
Oral herpes	Infections and infestations	—	—	—	—	—
Psoriatic arthropathy	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—

Most-reported serious reactions: Cellulitis, Thrombocytopenia, Coronary artery disease, Myocardial infarction, Colitis ulcerative, Crohn's disease, Diverticulum, Rectal haemorrhage.

Data from ClinicalTrials.gov NCT02404350 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy.
   Rayego-Mateos S, Morgado-Pascual JL, Opazo-Ríos L, Guerrero-Hue M, et al · · 2020 · cited 237× · PMID 32471207 · DOI 10.3390/ijms21113798
2. Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study.
   Mease P, van der Heijde D, Landewé R, Mpofu S, et al · · 2018 · cited 223× · PMID 29550766 · DOI 10.1136/annrheumdis-2017-212687
3. Association of Secukinumab Treatment With Tuberculosis Reactivation in Patients With Psoriasis, Psoriatic Arthritis, or Ankylosing Spondylitis.
   Elewski BE, Baddley JW, Deodhar AA, Magrey M, et al · · 2021 · cited 51× · PMID 33001147 · DOI 10.1001/jamadermatol.2020.3257
4. Secukinumab provides sustained low rates of radiographic progression in psoriatic arthritis: 52-week results from a phase 3 study, FUTURE 5.
   van der Heijde D, Mease PJ, Landewé RBM, Rahman P, et al · · 2020 · cited 41× · PMID 31586420 · DOI 10.1093/rheumatology/kez420
5. Secukinumab: A New Treatment Option for Psoriatic Arthritis.
   Mease P, McInnes IB. · · 2016 · cited 38× · PMID 27747518 · DOI 10.1007/s40744-016-0031-5
6. Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications.
   Merola JF, McInnes IB, Deodhar AA, Dey AK, et al · · 2022 · cited 32× · PMID 35305260 · DOI 10.1007/s40744-022-00434-z
7. Adverse events associated with anti-IL-17 agents for psoriasis and psoriatic arthritis: a systematic scoping review.
   Wang J, Wang C, Liu L, Hong S, et al · · 2023 · cited 25× · PMID 36817423 · DOI 10.3389/fimmu.2023.993057
8. Clinically relevant patient clusters identified by machine learning from the clinical development programme of secukinumab in psoriatic arthritis.
   Pournara E, Kormaksson M, Nash P, Ritchlin CT, et al · · 2021 · cited 25× · PMID 34795065 · DOI 10.1136/rmdopen-2021-001845