Clinical trial NCT02394561: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Plaque Type Psorisis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-03-20
Enrollment: 434
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arms represent stratification of Cw6 positive and Cw6 negative patients
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: Biological agents represent the most advanced type of treatment for psoriasis. Secukinumab is a human monoclonal anti IL-17A antibody that binds to human IL-17A and neutralizes its bioactivity by inhibiting IL17A produced by both Th17 cells and those of the innate immune system, thus providing complete anti IL17A blockage. Targeting IL-17A has the potential to reduce autoimmune inflammation while leaving other immune functions undisturbed. While targeting of Th1-promoting or Th17-promoting cytokines affects critical mediators such as IFN-γ, IL-22 and IL-21, selective targeting of IL-17A leaves these Th1/17 activities, as well as certain protective functions of innate cells intact. Furthermore, as a fully human monoclonal antibody, secukinumab should reduce immunogenic risks compared to current or emerging antibody therapies that are not fully human.

Many recent studies have shown that highly selective biologic drugs are not effective in every patient and that variations in the genome can be associated with different clinical responses or side effects to a given drug. The PSORS1 locus on chromosome 6p is generally understood to confer the most risk for psoriasis. A specific allele for this locus, HLA C\*06, is present in about 60% of psoriatic patient cases. Data linking secukinumab efficacy to a particular genetic marker are lacking.

Recent research has revealed a marked difference in the proportion of PASI 90 achievers at 12 weeks between Cw6-positive and Cw6-negative patients (85.7% vs 56.5%) treated with ustekinumab (Talamonti M et al. 2013) and a greater efficacy of anti-TNFα drugs in CW6 negative patients (Galli et al. 2013).Unlike anti-IL-12/23 agents, secukinumab inhibits IL-17 produced by both Th17 cells after presentation by antigen presenting cells (in this case Cw6) and cells of the innate immune system whose activation does not require antigen presentation. Providing a drug that is equally effective on both Cw6-negative and Cw6-positive patients would be an important clinical accomplishment and would eliminate the need for costly HLA-Cw6 tests. The choice of a cohort study would therefore seem appropriate for this clinical context.

The purpose of this study was to explore the different efficacy and safety profile of secukinumab 300 mg in patients with moderate to severe chronic plaque-type psoriasis, stratified for the presence of HLA-C\*06, whose determination was blinded for patients and investigators. The study was conducted both on anti-TNFα-naïve and anti-TNFα failure patients and also stratified for TNFα - 308 polymorphism, BMI, smoking and metabolic syndrome, among others.

Eligibility criteria: Inclusion Criteria:

1. Subject must have been able to understand and communicate with the investigator and to comply with the requirements of the study and must have given a written, signed and dated informed consent before any study related activity was performed.
2. Men or women at least 18 years of age at time of screening.
3. Diagnosis of moderate to severe chronic plaque-type psoriasis for at least 6 months (including concomitant psoriatic arthritis as per the Classification Criteria for Psoriatic Arthritis criteria \[CASPAR\]).
4. Moderate to severe psoriasis as defined at enrollment by:

   * PASI score ≥ 10 or
   * PASI score \> 5 but \< 10 and DLQI ≥10
5. Patients that are candidates for systemic therapy, whether treatment naïve or after failed response to other systemic therapy (i.e. cyclosporine, methotrexate and PUVA) or to an anti-TNFα (or is intolerant and/or has a contraindication to these).

Exclusion criteria

1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis).
2. Cyclosporine or methotrexate therapy within 4 weeks prior to Day 1.
3. Anti-TNFα therapy within timelines depending on drug half-life.
4. Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or the IL-17 receptor.
5. Previous exposure to ustekinumab or any other biologic drug for the treatment of psoriasis that was not anti-TNFα therapy.
6. Intravenous or intramuscular steroids within 2 weeks prior to screening and during screening.
7. Ongoing use of corticosteroid topical treatments or UV therapy.

Primary outcomes:
measure: Percentage (%) of Patients Who Reach Psoriasis Area Severity Index (PASI) 90 at 16 Weeks - LOCF Approach (ITT Set)
timeFrame: Baseline up to 16 weeks
Secondary outcomes:
measure: Percentage (%) of Patients With IGA 0/1, PASI 50, PASI 75, PASI 90, PASI 100 Responders by Visit - LOCF Approach (ITT Set)
timeFrame: Baseline up to approximately 72 weeks
measure: Percent Mean Changes From Baseline in IGA Mod 2011 Between Cohorts at Each Time Point (LOCF) (ITT)
timeFrame: Baseline up to approximately 72 weeks
measure: Median Time to Reach PASI 90 and 75 (ITT)
timeFrame: Baseline up to approximately 72 weeks
measure: Change From Baseline in the Dermatology Life Quality Index (DLQI) (LOCF) (FAS)
timeFrame: Baseline up to approximatly 72 weeks
measure: Change From Baseline in Mean Scores of HAD-A and HAD-D (Anxiety and Depression) (LOCF) (FAS)
timeFrame: Baseline up approximately 72 weeks
measure: Correlation Between the Hospital Anxiety and Depression Scale (HADS) and PASI (FAS)
timeFrame: Baseline up to approximately 72 weeks
measure: Changes From Baseline in Body Mass Index (Safety Set)
timeFrame: Baseline up to approximately 72 weeks
measure: Changes From Baseline in Waist Circumference (Safety Set)
timeFrame: Baseline up to approximately 72 weeks
measure: Changes From Baseline in Weight (Safety Set)
timeFrame: Baseline up to approximately 72 weeks
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Novartis Investigative Site
state: (mi)
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: L'Aquila
country: Italy
facility: Novartis Investigative Site
state: AQ
city: Bari
country: Italy
facility: Novartis Investigative Site
state: BA
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: BG
city: Benevento
country: Italy
facility: Novartis Investigative Site
state: BN
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Brindisi
country: Italy
facility: Novartis Investigative Site
state: BR
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Cagliari
country: Italy
facility: Novartis Investigative Site
state: CA
city: Chieti
country: Italy
facility: Novartis Investigative Site
state: CH
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Catanzaro
country: Italy
facility: Novartis Investigative Site
state: CZ
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Grosseto
country: Italy
facility: Novartis Investigative Site
state: GR
city: Lecce
country: Italy
facility: Novartis Investigative Site
state: LE
city: Terracina
country: Italy
facility: Novartis Investigative Site
state: LT
city: Lucca
country: Italy
facility: Novartis Investigative Site
state: LU
city: Macerata
country: Italy
facility: Novartis Investigative Site
state: MC
city: Messina
country: Italy
facility: Novartis Investigative Site
state: ME
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: San Donato Milanese
country: Italy
facility: Novartis Investigative Site
state: MI
city: Mantova
country: Italy
facility: Novartis Investigative Site
state: MN
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Reggio Emilia
country: Italy
facility: Novartis Investigative Site
state: RE
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Erice
country: Italy
facility: Novartis Investigative Site
state: TP
city: Terni
country: Italy
facility: Novartis Investigative Site
state: TR
city: Trieste
country: Italy
facility: Novartis Investigative Site
state: TS
city: Udine
country: Italy
facility: Novartis Investigative Site
state: UD
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Napoli
country: Italy
facility: Novartis Investigative Site
Study officials:
References: