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)

• ClinicalTrials.gov Identifier: NCT03020199
• Recruitment Status: Active, not recruiting
• First Posted: January 13, 2017
• Last Update Posted: December 9, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Plaque Psoriasis	Biological: Secukinumab; Radiation: nbUVB; Drug: Calcipotriol; Drug: Betamethasone	Phase 4

Detailed Description:

The overall study population (Main Study and Mechanistic Sub-study) will consist of a total of 205 male and female patients aged between 18 and 40 years inclusive.

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 50 sites worldwide. Since a maximum screening failure rate of 20% is expected, approximately 200 patients will be screened.

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 (15 patients each). For Arm A1b or Arm B1b, the first 15 patients will be included on a first come first serve basis.

Safety assessments :Physical examination, Vital signs, Height and body weight, Laboratory evaluations (hematology, clinical chemistry, high-sensitivity C-reactive protein), Electrocardiogram, Pregnancy, Adverse events

Data Analysis The primary efficacy variable is the proportion of patients who achieve PASI 90 at Week 52. The analysis for the primary objective will be based on the full analysis set. For the primary analysis, the following hypothesis testing will be performed: H01: psec = pnbUVB versus HA1: psec ≠ pnbUVB The primary analysis method for PASI 90 response at Week 52 will use an exact logistic regression model with treatment as an explanatory variable and baseline PASI score as covariate. The key secondary variable is the proportion of all randomized patients who achieve PASI 90 at Week 104. In order to reduce selection bias, all patients who do not achieve PASI 90 at Week 52 will also be included in the analysis at Week 104 using the PASI improvement obtained at Week 104 only.

For the key secondary analysis, the following hypothesis testing will be performed:

H02: p*sec = p*nbUVB versus HA2: p*sec ≠ p*nbUVB

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 196 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: March 27, 2017
• Estimated Primary Completion Date: July 30, 2021
• Estimated Study Completion Date: August 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: A1; 80 patients (65 in Arm A1a and 15 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.	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.
Active Comparator: B1; 80 patients (65 in Arm B1a and 15 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.	Radiation: nbUVB; 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; 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
Experimental: A2; secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 and 4; and thereafter every 4 weeks until Week 100 inclusive (last dose administered at Week 100)	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
Experimental: C1; secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 and 4; and thereafter every 4 weeks until Week 48 inclusive (last dose administered at Week 48)	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
Experimental: C2; secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 and 4; and thereafter every 4 weeks until Week 100 inclusive (last dose administered at Week 100)	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

Outcome Measures

Primary Outcome Measures :

1. The primary efficacy variable is the proportion of patients who achieve Pain Assessment Severity Index (PASI) 90 at Week 52. PASI is measured by dermatologist usung a PASI measurement scale. [ Time Frame: 52 weeks ]
   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.

Secondary Outcome Measures :

1. The key secondary variable is the proportion of all randomized patients who achieve PASI 90 at Week 104 [ Time Frame: 104 weeks ]
   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.

Eligibility Criteria

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

Criteria

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 40 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 (Arms A1, A2 and Arm B1)
• 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 investigator's global assessment (IGA mod 2011) ≥ 3

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 Epoch or longer if required by locally-approved prescribing information (e.g., 20 weeks in the EU)

Contacts and Locations

Locations

Argentina

Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, Argentina, 1181

Novartis Investigative Site

Buenos Aires, Argentina, C1425DKG

Bulgaria

Novartis Investigative Site

Pleven, Bulgaria, 5800

Novartis Investigative Site

Plovdiv, Bulgaria, 4002

Novartis Investigative Site

Sofia, Bulgaria, 1407

Novartis Investigative Site

Sofia, Bulgaria, 1632

Canada, Ontario

Novartis Investigative Site

Markham, Ontario, Canada, L3P 1X2

Novartis Investigative Site

Sudbury, Ontario, Canada, P3C 1X8

Denmark

Novartis Investigative Site

Aarhus, Denmark, 8000

Estonia

Novartis Investigative Site

Tallinn, Estonia, 10138

Novartis Investigative Site

Tallinn, Estonia, 13419

Novartis Investigative Site

Tartu, Estonia, 51014

Finland

Novartis Investigative Site

Tampere, Finland, 33100

Novartis Investigative Site

Turku, Finland, FIN-20100

Germany

Novartis Investigative Site

Berlin, Germany, 10789

Novartis Investigative Site

Berlin, Germany, 13353

Novartis Investigative Site

Erlangen, Germany, 91054

Novartis Investigative Site

Frankfurt, Germany, 60590

Hungary

Novartis Investigative Site

Nyíregyháza, Hungary, 4400

Novartis Investigative Site

Szolnok, Hungary, 5000

Poland

Novartis Investigative Site

Bialystok, Poland, 15-879

Novartis Investigative Site

Bydgoszcz, Poland, 85-094

Novartis Investigative Site

Gdansk, Poland, 80 952

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

Lublin, Poland, 20-079

Spain

Novartis Investigative Site

Barcelona, Cataluna, Spain, 08036

Novartis Investigative Site

Alicante, Comunidad Valenciana, Spain, 03010

Novartis Investigative Site

Alcorcon, Madrid, Spain, 28922

Novartis Investigative Site

Barcelona, Spain, 08003

Novartis Investigative Site

Barcelona, Spain, 08025

Novartis Investigative Site

Las Palmas de Gran Canaria, Spain, 35010

Novartis Investigative Site

Madird, Spain, 28041

Novartis Investigative Site

Madrid, Spain, 28031

Novartis Investigative Site

Valencia, Spain, 46014

Sweden

Novartis Investigative Site

Goethenburg, Sweden

Novartis Investigative Site

Malmo, Sweden, 214 28

Switzerland

Novartis Investigative Site

Lausanne, Switzerland, CH-1011

United Kingdom

Novartis Investigative Site

Bradford, West Yorkshire, United Kingdom, BD5 0NA

Novartis Investigative Site

Leeds, West Yorkshire, United Kingdom, LS7 4SA

Novartis Investigative Site

London, United Kingdom, SE1 9RT

Novartis Investigative Site

Salford, United Kingdom, M6 8HD

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03020199
• Other Study ID Numbers: CAIN457A2322
• First Posted: January 13, 2017
• Last Update Posted: December 9, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Psoriasis

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Betamethasone; Calcipotriene; Antibodies, Monoclonal; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Immunologic Factors; Dermatologic Agents