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NCT02394561: SUPREME

A 24-week, Multicenter, proSpective stUdy to Evaluate the PASI 90 Clinical Response Rate and the Safety PRofile of sEcukinuMab 300 mg in Cw6-negativE and Cw6-positive Patients With Moderate to Severe Chronic Plaque-type Psoriasis (SUPREME)

Completed Phase 3 Results posted Last updated 23 April 2019
What this trial tests

Phase 3 trial testing Secukinumab in Plaque Type Psorisis in 434 participants. Completed in 8 June 2017.

Timeline
10 April 2015
Primary endpoint
8 June 2017
8 June 2017

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment434
Start date10 April 2015
Primary completion8 June 2017
Estimated completion8 June 2017
Sites45 locations across Italy

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Plaque Type Psorisis. 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 Patients Who Reach Psoriasis Area Severity Index (PASI) 90 at 16 Weeks - LOCF Approach (ITT Set) Primary · Baseline up to 16 weeks

PASI (Langley et al 2015) combines the assessment of the severity of lesions and the area affected into a single score with a range of 0 (no disease) to 72 (maximal disease). The PASI was assessed at all visits in CORE and extension phases. PASI 90 response: patients achieving ≥ 90% improvement (reduction) in PASI score compared to baseline are defined as PASI 90 responders.

GroupValue95% CI
Cw6-positive AIN457 300 mg80.474.0 – 85.9
Cw6-negative AIN457 300 mg81.776.3 – 86.3
Percentage (%) of Patients With IGA 0/1, PASI 50, PASI 75, PASI 90, PASI 100 Responders by Visit - LOCF Approach (ITT Set) Secondary · Baseline up to approximately 72 weeks

IGA mod 2011 scale measures severity of the psoriasis on a five-point scale ranging from 0 (no disease, 'clear') to 4 ('very severe'). PASI 50,75,90,100 represent: patients achieving ≥ 50% improvement (reduction) in PASI score compared to baseline, ≥ 75% improvement (reduction), ≥ 90% improvement (reduction) and PASI 100 response/remission: complete clearing of psoriasis (PASI=0).

W1 IGA 0/1
GroupValue95% CI
Cw6-positive AIN457 300 mg2.20.62 – 5.65
Cw6-negative AIN457 300 mg2.10.68 – 4.79
Difference in % (Cw6-pos vs Cw6-neg)0.16-2.86 – 3.75
W1 PASI 50
GroupValue95% CI
Cw6-positive AIN457 300 mg13.48.78 – 19.29
Cw6-negative AIN457 300 mg12.18.24 – 16.89
Difference in % (Cw6-pos vs Cw6-neg)1.32-5.02 – 8.09
W1 PASI 75
GroupValue95% CI
Cw6-positive AIN457 300 mg2.20.61 – 5.62
Cw6-negative AIN457 300 mg0.40.01 – 2.30
Difference in % (Cw6-pos vs Cw6-neg)1.82-0.52 – 5.20
W2 IGA 0/1
GroupValue95% CI
Cw6-positive AIN457 300 mg8.75.05 – 13.74
Cw6-negative AIN457 300 mg6.94.08 – 10.83
Difference in % (Cw6-pos vs Cw6-neg)1.79-3.29 – 7.36
W2 PASI 50
GroupValue95% CI
Cw6-positive AIN457 300 mg44.036.73 – 51.51
Cw6-negative AIN457 300 mg44.538.16 – 50.95
Difference in % (Cw6-pos vs Cw6-neg)-0.47-9.84 – 8.98
W2 PASI 75
GroupValue95% CI
Cw6-positive AIN457 300 mg15.810.82 – 21.84
Cw6-negative AIN457 300 mg10.26.71 – 14.69
Difference in % (Cw6-pos vs Cw6-neg)5.56-0.80 – 12.32
W2 PASI 90
GroupValue95% CI
Cw6-positive AIN457 300 mg3.31.21 – 6.96
Cw6-negative AIN457 300 mg2.40.90 – 5.25
Difference in % (Cw6-pos vs Cw6-neg)0.81-2.49 – 4.71
W2 PASI 100
GroupValue95% CI
Cw6-positive AIN457 300 mg0.50.01 – 2.99
Cw6-negative AIN457 300 mg0.40.01 – 2.25
Difference in % (Cw6-pos vs Cw6-neg)0.14-1.78 – 2.63
Percent Mean Changes From Baseline in IGA Mod 2011 Between Cohorts at Each Time Point (LOCF) (ITT) Secondary · Baseline up to approximately 72 weeks

IGA mod 2011 scale measures severity of the psoriasis on a five-point scale ranging from 0 (no disease, 'clear') to 4 ('very severe').

W1
GroupValue95% CI
Cw6-positive AIN457 300 mg-8.5± 16.08
Cw6-negative AIN457 300 mg-7.3± 17.04
W2
GroupValue95% CI
Cw6-positive AIN457 300 mg-22.4± 22.73
Cw6-negative AIN457 300 mg-21.6± 22.72
W3
GroupValue95% CI
Cw6-positive AIN457 300 mg-38.0± 25.45
Cw6-negative AIN457 300 mg-36.5± 27.20
W4
GroupValue95% CI
Cw6-positive AIN457 300 mg-49.6± 29.36
Cw6-negative AIN457 300 mg-49.5± 29.24
W8
GroupValue95% CI
Cw6-positive AIN457 300 mg-71.2± 28.60
Cw6-negative AIN457 300 mg-71.2± 28.91
W12
GroupValue95% CI
Cw6-positive AIN457 300 mg-78.7± 27.31
Cw6-negative AIN457 300 mg-79.0± 25.37
W16
GroupValue95% CI
Cw6-positive AIN457 300 mg-84.1± 24.52
Cw6-negative AIN457 300 mg-83.3± 22.97
W20
GroupValue95% CI
Cw6-positive AIN457 300 mg-85.3± 24.26
Cw6-negative AIN457 300 mg-84.5± 23.80
Median Time to Reach PASI 90 and 75 (ITT) Secondary · Baseline up to approximately 72 weeks

Time in days to reach PASI scores of 90 and 75.

PASI 90
GroupValue95% CI
Cw6-positive AIN457 300 mg5730 – 89
Cw6-negative AIN457 300 mg5855 – 92
PASI 75
GroupValue95% CI
Cw6-positive AIN457 300 mg2922 – 57
Cw6-negative AIN457 300 mg2922 – 57
Change From Baseline in the Dermatology Life Quality Index (DLQI) (LOCF) (FAS) Secondary · Baseline up to approximatly 72 weeks

The DLQI total score was calculated by summing the score of each domain resulting in a maximum of 30 and a minimum of 0. The higher the score, the more Quality of Life was impaired. Meaning of DLQI Scores: 0-1 = no effect at all on patient's life, 2-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20= very large effect on patient's life, 21-30 = extremely large effect on patient's life. It was pre-specified that results would be presented for all patients, not by cohort

Week 16
GroupValue95% CI
All Patients-8.5± 6.79
Week 24
GroupValue95% CI
All Patients-8.8± 7.05
Week 48
GroupValue95% CI
All Patients-8.9± 7.13
Week 72
GroupValue95% CI
All Patients-8.3± 6.70
Change From Baseline in Mean Scores of HAD-A and HAD-D (Anxiety and Depression) (LOCF) (FAS) Secondary · Baseline up approximately 72 weeks

The Hospital Anxiety and Depression Scale (HADS) is a fourteen-item scale.. Seven of the items relate to anxiety and seven relate to depression. This outcome measure was specifically developed to avoid reliance on aspects of these conditions that are also common somatic symptoms of illness, for example fatigue and insomnia or hypersomnia. Calculations of scores: each of the 14 items was rated on a 4-point scale. All items except 7 and 10 were scored as Yes, definitely = 3, Yes, sometimes = 2, No, not much = 1, to No, not at all = 0. Items 7 and 10 were scored as Yes, definitely = 0 to No, not

W16 Anxiety
GroupValue95% CI
All Patients-1.7± 3.37
W24 Anxiety
GroupValue95% CI
All Patients-2.0± 3.38
W48 Anxiety
GroupValue95% CI
All Patients-2.5± 3.67
W72 Anxiety
GroupValue95% CI
All Patients-2.3± 3.44
W16 Depression
GroupValue95% CI
All Patients-1.3± 3.19
W24 Depression
GroupValue95% CI
All Patients-1.4± 3.22
W48 Depression
GroupValue95% CI
All Patients-1.5± 3.31
W72 Depression
GroupValue95% CI
All Patients-1.7± 3.19
Correlation Between the Hospital Anxiety and Depression Scale (HADS) and PASI (FAS) Secondary · Baseline up to approximately 72 weeks

PASI score, HADS questionnaire correlation using Spearman rank correlation coefficient. It was pre-specified that results would be presented for all patients, not by cohort

Baseline
GroupValue95% CI
All Patients0.02
Week 16
GroupValue95% CI
All Patients0.19
Week 24
GroupValue95% CI
All Patients0.18
Week 48
GroupValue95% CI
All Patients0.21
Week 72
GroupValue95% CI
All Patients0.32
Changes From Baseline in Body Mass Index (Safety Set) Secondary · Baseline up to approximately 72 weeks

Change in Body mass index from baseline for patients with a value at baseline and the respective post-baseline visit

Week 16
GroupValue95% CI
Cw6-positive AIN457 300 mg-0.064± 0.7748
Cw6-negative AIN457 300 mg-0.047± 0.9905
Week 24
GroupValue95% CI
Cw6-positive AIN457 300 mg0.086± 1.0213
Cw6-negative AIN457 300 mg-0.071± 1.2260
Week 48
GroupValue95% CI
Cw6-positive AIN457 300 mg0.302± 1.3474
Cw6-negative AIN457 300 mg-0.052± 1.4991
Week 72
GroupValue95% CI
Cw6-positive AIN457 300 mg0.533± 1.8101
Cw6-negative AIN457 300 mg-0.015± 1.8982
Changes From Baseline in Waist Circumference (Safety Set) Secondary · Baseline up to approximately 72 weeks

Change in waist circumference from baseline for patients with a value at baseline and the respective post-baseline visit

Week 16
GroupValue95% CI
Cw6-positive AIN457 300 mg-0.86± 3.147
Cw6-negative AIN457 300 mg-0.40± 3.006
Week 24
GroupValue95% CI
Cw6-positive AIN457 300 mg-0.81± 3.689
Cw6-negative AIN457 300 mg-0.73± 4.119
Week 48
GroupValue95% CI
Cw6-positive AIN457 300 mg-0.76± 4.596
Cw6-negative AIN457 300 mg-0.72± 5.547
Week 72
GroupValue95% CI
Cw6-positive AIN457 300 mg-1.81± 4.583
Cw6-negative AIN457 300 mg-0.47± 4.501
Changes From Baseline in Weight (Safety Set) Secondary · Baseline up to approximately 72 weeks

Change in weight from baseline for patients with a value at baseline and the respective post-baseline visit

Week 16
GroupValue95% CI
Cw6-positive AIN457 300 mg-0.20± 2.242
Cw6-negative AIN457 300 mg-0.13± 2.809
Week 24
GroupValue95% CI
Cw6-positive AIN457 300 mg0.24± 3.008
Cw6-negative AIN457 300 mg-0.21± 3.572
Week 48
GroupValue95% CI
Cw6-positive AIN457 300 mg0.87± 3.909
Cw6-negative AIN457 300 mg-0.15± 4.329
Week 72
GroupValue95% CI
Cw6-positive AIN457 300 mg1.40± 4.678
Cw6-negative AIN457 300 mg-0.05± 5.538

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 72 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cw6-Negative AIN457 300 mg
Serious: 21/246 (9%)
Deaths: 2/246
Cw6-Positive AIN457 300 mg
Serious: 10/185 (5%)
Deaths: 0/185

Serious adverse events (39 terms)

ReactionSystemCw6-Negative AIN457 300 mgCw6-Positive AIN457 300 mg
HyperbilirubinaemiaHepatobiliary disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood bilirubin increasedInvestigations
LeukopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
Abdominal pain upperGastrointestinal disorders
AstheniaGeneral disorders
Non-cardiac chest painGeneral disorders
PyrexiaGeneral disorders
CholelithiasisHepatobiliary disorders
Hepatic lesionHepatobiliary disorders
HypertransaminasaemiaHepatobiliary disorders
GastroenteritisInfections and infestations
Perirectal abscessInfections and infestations
Urinary tract infectionInfections and infestations
Vulvovaginal candidiasisInfections and infestations
Lipase increasedInvestigations
HypertriglyceridaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
EnthesopathyMusculoskeletal and connective tissue disorders
Meniscal degenerationMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Other adverse events (2 terms — click to expand)

ReactionSystemCw6-Negative AIN457 300 mgCw6-Positive AIN457 300 mg
PruritusSkin and subcutaneous tissue disorders
HypertensionVascular disorders

Most-reported serious reactions: Hyperbilirubinaemia, Alanine aminotransferase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Leukopenia, Neutropenia, Thrombocytopenia, Cardiac arrest.

Data from ClinicalTrials.gov NCT02394561 adverse events section.

Sponsor's own description

A study to evaluate the differences in the efficacy and safety of secukinumab between Cw6-negative and Cw6-positive patients with moderate to severe plaque-type psoriasis

Publications & conference data

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

  1. Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study.
    Russo F, Galluzzo M, Stingeni L, Persechino S, et al · · 2023 · cited 8× · PMID 38107670 · DOI 10.2147/ccid.s416149
  2. Secukinumab Exhibits Sustained and Stable Response in Patients with Moderate-to-Severe Psoriasis: Results from the SUPREME Study.
    Costanzo A, Russo F, Galluzzo M, Stingeni L, et al · · 2021 · cited 8× · PMID 33903916 · DOI 10.2340/00015555-3816
  3. Efficacy and Safety of Secukinumab in Elderly Patients with Moderate to Severe Plaque-Type Psoriasis: Post-Hoc Analysis of the SUPREME Study.
    Talamonti M, Russo F, Malara G, Hansel K, et al · · 2023 · cited 7× · PMID 37033782 · DOI 10.2147/ccid.s400520
  4. Efficacy of Secukinumab in Psoriasis: Post Hoc Gender-Wise Analysis of the SUPREME Study.
    Stingeni L, Malara G, Conti A, Di Costanzo L, et al · · 2023 · cited 5× · PMID 36636635 · DOI 10.2147/ccid.s378135

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