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)

NCT ID: NCT02394561

Last Updated: 2019-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 434 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-10
• Study Completion Date: 2017-06-08

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.

Conditions

Plaque Type Psorisis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cw6-positive AIN457 300 mg

Stratified to Cw6 positive cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks

Group Type: EXPERIMENTAL

Secukinumab

Intervention Type: BIOLOGICAL

Secukinumab was supplied as 150 mg solution in pre-filled syringe for subcutaneous injection

Cw6-negative AIN457 300 mg

Stratified to Cw6 negative cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks

Group Type: EXPERIMENTAL

Secukinumab

Intervention Type: BIOLOGICAL

Secukinumab was supplied as 150 mg solution in pre-filled syringe for subcutaneous injection

Interventions

Secukinumab

Secukinumab was supplied as 150 mg solution in pre-filled syringe for subcutaneous injection

Intervention Type: BIOLOGICAL

Other Intervention Names

AIN457

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novartis Investigative Site

Milan, (MI), Italy

Novartis Investigative Site

Ancona, AN, Italy

Novartis Investigative Site

L’Aquila, AQ, Italy

Novartis Investigative Site

Bari, BA, Italy

Novartis Investigative Site

Bergamo, BG, Italy

Novartis Investigative Site

Benevento, BN, Italy

Novartis Investigative Site

Bologna, BO, Italy

Novartis Investigative Site

Brindisi, BR, Italy

Novartis Investigative Site

Brescia, BS, Italy

Novartis Investigative Site

Cagliari, CA, Italy

Novartis Investigative Site

Chieti, CH, Italy

Novartis Investigative Site

Catania, CT, Italy

Novartis Investigative Site

Catanzaro, CZ, Italy

Novartis Investigative Site

Florence, FI, Italy

Novartis Investigative Site

Genova, GE, Italy

Novartis Investigative Site

Grosseto, GR, Italy

Novartis Investigative Site

Lecce, LE, Italy

Novartis Investigative Site

Terracina, LT, Italy

Novartis Investigative Site

Lucca, LU, Italy

Novartis Investigative Site

Macerata, MC, Italy

Novartis Investigative Site

Messina, ME, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

San Donato Milanese, MI, Italy

Novartis Investigative Site

Mantova, MN, Italy

Novartis Investigative Site

Modena, MO, Italy

Novartis Investigative Site

Padua, PD, Italy

Novartis Investigative Site

Perugia, PG, Italy

Novartis Investigative Site

Pisa, PI, Italy

Novartis Investigative Site

Parma, PR, Italy

Novartis Investigative Site

Pavia, PV, Italy

Novartis Investigative Site

Reggio Emilia, RE, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Siena, SI, Italy

Novartis Investigative Site

Torino, TO, Italy

Novartis Investigative Site

Erice, TP, Italy

Novartis Investigative Site

Terni, TR, Italy

Novartis Investigative Site

Trieste, TS, Italy

Novartis Investigative Site

Udine, UD, Italy

Novartis Investigative Site

Verona, VR, Italy

Novartis Investigative Site

Napoli, , Italy

Countries

Italy

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CAIN457AIT01

Identifier Type: -

Identifier Source: org_study_id