Study of the Efficacy of Early Intervention With Secukinumab 300 mg s.c. Compared to Narrow-band UVB in Patients With New-onset Moderate to Severe Plaque Psoriasis (STEPin)

A Randomized, Multicenter STudy to Evaluate the Effect of Secukinumab 300 mg s.c. Administered During 52 Weeks to Patients Suffering From New-onset Moderate to Severe Plaque Psoriasis as Early Intervention Compared to Standard Treatment With Narrow-band UVB (STEPIn Study)

The purpose of this study is to determine whether early intervention with subcutaneous (s.c.) secukinumab 300 mg in patients with new-onset moderate to severe plaque psoriasis may lead to prolonged symptom-free periods by preventing reactivation of old lesions or ultimately totally hindering the occurrence of new lesions, i.e., changing the natural course of the disease (Main Study).

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Biological: Secukinumab; Drug: Calcipotriol; Drug: Betamethasone; Radiation: nb-UVB

Detailed Description

The design consists of the Main Study and a Mechanistic Sub study:

1. The Main Study will be multicenter, randomized, 2-treatment-arm (secukinumab and nb-UVB), parallel-group and open-label. It will include 3 clinical periods (Screening period, Treatment period, and Follow-up period) involving all patients in Arms A1 (A1a and A1b) and B1 (B1a and B1b).
2. The Mechanistic Sub-study will be open-label and comprise 5 treatment arms (A1b, A2, B1b, C1, and C2). It will include 2 periods (Screening period and Treatment period) for patients in Arms C1, C2 and A2. Patients from Arms A1b and B1b will undergo the 3 clinical periods of the Main Study.

The overall study population (Main Study and Mechanistic Sub-study) will consist of a total of 196 male and female patients aged between 18 and 50 years inclusive.

1. Main Study The Main Study will be conducted in patients with new-onset moderate to severe plaque psoriasis not previously treated with any systemic treatment or phototherapy.

   A total of 160 patients will be randomized to Arm A1 or Arm B1 in approximately 75 sites worldwide. Since a maximum screening failure rate of 20% is expected, approximately 245 patients will be screened.

2. Mechanistic Sub-study Any patient who consents can participate in the Mechanistic Sub-study. Patients with new-onset plaque psoriasis will be randomized to Arm A1b, Arm A2, or Arm B1b, those with chronic plaque psoriasis will be randomized to Arm C1 and Arm C2 (12 patients each).

For Arm A1b or Arm B1b, the first 12 patients will be included on a first come first serve basis.

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425DKG
    • Novartis Investigative Site
  • Buenos Aires
    • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, 1181
      • Novartis Investigative Site
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Novartis Investigative Site
  • Plovdiv, Bulgaria, 4002
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1407
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1632
    • Novartis Investigative Site
• Canada
  • Ontario
    • Markham, Ontario, Canada, L3P 1X2
      • Novartis Investigative Site
    • Sudbury, Ontario, Canada, P3C 1X8
      • Novartis Investigative Site
• Denmark
  • Aarhus, Denmark, 8000
    • Novartis Investigative Site
• Estonia
  • Tallinn, Estonia, 13419
    • Novartis Investigative Site
  • Tallinn, Estonia, 10138
    • Novartis Investigative Site
  • Tartu, Estonia, 50406
    • Novartis Investigative Site
• Finland
  • Tampere, Finland, 33100
    • Novartis Investigative Site
  • Turku, Finland, FIN-20100
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Berlin, Germany, 10789
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
• Hungary
  • Nyiregyhaza, Hungary, 4400
    • Novartis Investigative Site
  • Szolnok, Hungary, 5000
    • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15-879
    • Novartis Investigative Site
  • Bydgoszcz, Poland, 85-094
    • Novartis Investigative Site
  • Gdansk, Poland, 80-803
    • Novartis Investigative Site
  • Krakow, Poland, 31-070
    • Novartis Investigative Site
  • Lodz, Poland, 90-436
    • Novartis Investigative Site
  • Lodz, Poland, 90-647
    • Novartis Investigative Site
• Spain
  • Las Palmas de Gran Canaria, Spain, 35010
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28031
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03010
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46014
      • Novartis Investigative Site
  • Madrid
    • Alcorcon, Madrid, Spain, 28922
      • Novartis Investigative Site
• Sweden
  • Goethenburg, Sweden, 413 45
    • Novartis Investigative Site
  • Malmo, Sweden, 214 28
    • Novartis Investigative Site
• Switzerland
  • Lausanne, Switzerland, CH-1011
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Novartis Investigative Site
  • Salford, United Kingdom, M6 8HD
    • Novartis Investigative Site
  • West Yorkshire
    • Bradford, West Yorkshire, United Kingdom, BD5 0NA
      • Novartis Investigative Site
    • Leeds, West Yorkshire, United Kingdom, LS7 4SA
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Able to understand and communicate with the investigator, willing and capable to comply with all study procedures, and provide written signed and dated informed consent (personally or by a witness) before any assessment is performed.
• Aged 18 to 50 years inclusive.
• New-onset plaque psoriasis with appearance of the first psoriasis plaques within the last 12 months before randomization and naïve to any systemic treatment and phototherapy (Arm A1, Arm A2, and Arm B1). Episodes of mild psoriasis, which occurred at least 3 years before screening and resolved spontaneously within 6 months will be accepted.
• Chronic plaque psoriasis with appearance of the first psoriasis symptoms 5 years or longer and intolerance or inadequate response to phototherapy or any systemic treatment including biologicals, except for IL-17A inhibitors (Arm C1 and Arm C2).
• Moderate to severe plaque psoriasis defined at screening and baseline by PASI >= 10, and body surface area (BSA) >= 10%, and IGA mod 2011 >= 3.

Key Exclusion Criteria:

• Forms of psoriasis other than plaque-type (e.g., pustular, erythrodermic, guttate, light sensitive, and drug induced).
• Ongoing use of prohibited treatments.
• Previous treatment with phototherapy or any systemic treatment.
• Pregnant or nursing (lactating) women.
• Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during the Treatment period or longer if required by locally approved prescribing information (e.g., 20 weeks in the EU and countries where applicable for secukinumab).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A1 (A1a and A1b): new-onset plaque psoriasis to be treated with secukinumab; 80 patients (68 in Arm A1a and 12 in Arm A1b) with new-onset psoriasis will receive 300 mg secukinumab by s.c. injection at baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 48 inclusive (treatment duration = 52 weeks).	Biological: Secukinumab; Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL.; Other Names: AIN457
Active Comparator: Arm B1 (B1a and B1b): new-onset plaque psoriasis to be treated with nb-UVB; 80 patients (68 in Arm B1a and 12 in Arm B1b) with new-onset psoriasis will receive 1 or 2 cycles of nb UVB of 12 weeks each with a maximum break of 28 weeks between cycles (patients with PASI 90 at Week 40 will not receive a second treatment cycle). Only during the first 4 weeks of each cycle, nb-UVB treatment should be applied in combination with topical calcipotriol 50 µg/g and betamethasone 0.5 mg/g (treatment duration = 52 weeks).	Drug: Calcipotriol; Its a topical treatment for Psoriasis. the concentration it is used is 50mcg/g; Drug: Betamethasone; this is topical cream which is used in 0.5mg/g concentration; Radiation: nb-UVB; Narrow-band UVB applied in 1 or 2 cycles, each comprising a period of 12 weeks with 2 to 3 treatment sessions per week totaling 24 to 36 sessions per cycle. The application will be performed according to the investigational site's protocol, taking into account the patient's skin type. A maximum dose of 3 J/cm2 on the body and 1 J/cm2 on the face is recommended
Experimental: Arm A2: new-onset plaque psoriasis to be treated with secukinumab; Eligible patients with new-onset psoriasis will receive 300 mg secukinumab by s.c. injection at baseline, Weeks 1, 2, 3 and 4 and then every 4 weeks until Week 100 inclusive (last dose administered at Week 100) (treatment duration = 104 weeks).	Biological: Secukinumab; Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL.; Other Names: AIN457
Experimental: Arm C1: chronic plaque psoriasis to be treated with secukinumab; Eligible patients with chronic plaque psoriasis will receive 300 mg secukinumab by s.c. injection at baseline, Weeks 1, 2, 3 and 4 and then every 4 weeks until Week 48 inclusive (last dose administered at Week 48) (treatment duration = 52 weeks).	Biological: Secukinumab; Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL.; Other Names: AIN457
Experimental: Arm C2: chronic plaque psoriasis to be treated with secukinumab; Eligible patients with chronic plaque psoriasis will receive 300 mg secukinumab by s.c. injection at baseline, Weeks 1, 2, 3 and 4 and then every 4 weeks until Week 100 inclusive (last dose administered at Week 100) (treatment duration = 104 weeks).	Biological: Secukinumab; Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL.; Other Names: AIN457

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who achieve Pain Assessment Severity Index (PASI) 90 at Week 52.	The primary objective of this study is to demonstrate that early treatment with secukinumab 300 mg s.c. (Arm A1) is superior to standard of care treatment with nb UVB (Arm B1) in patients with new onset moderate to severe plaque psoriasis with respect to patients achieving ≥ 90% improvement (reduction) in psoriasis area and severity index (PASI 90) response at Week 52. PASI takes into account the extent of the disease, as well as the severity of erythema, scaling, and thickness in different body areas affected by psoriasis. A PASI 90 represents an improvement in the PASI score of at least 90% as compared with baseline.	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of all randomized patients who achieve PASI 90 at Week 104	The key secondary objective of this study is to evaluate the superiority of early treatment with secukinumab (Arm A1) versus nb UVB (Arm B1) based on the proportion of all randomized patients who achieve at least PASI 90 at Week 104. PASI takes into account the extent of the disease, as well as the severity of erythema, scaling, and thickness in different body areas affected by psoriasis. A PASI 90 represents an improvement in the PASI score of at least 90% as compared with baseline.	Week 104

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2017
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): June 16, 2023

Study Registration Dates

• First Submitted: September 23, 2016
• First Submitted That Met QC Criteria: January 11, 2017
• First Posted (Estimated): January 13, 2017

Study Record Updates

• Last Update Posted (Actual): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Psoriasis; PASI; AIN457; secukinumab; Psoriasis area and severity index; IL-17A; interleukin (IL) 17A; Narrow-band ultraviolet light B; nb-UVB
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Anti-Asthmatic Agents; Respiratory System Agents; Betamethasone; Calcipotriene
• Other Study ID Numbers: CAIN457A2322; 2015-002423-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No