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)

Novartis

Status and phase: Completed; Phase 4

Conditions: Plaque Psoriasis

Treatments: Drug: Calcipotriol; Drug: Betamethasone; Biological: Secukinumab; Radiation: nb-UVB

Study type: Interventional

Funder types: Industry

Identifiers

NCT03020199

2015-002423-26 (EudraCT Number)

CAIN457A2322

Details and patient eligibility

About

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).

Full description

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

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). 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.

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.

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.

Enrollment: 196 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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196 participants in 5 patient groups

Arm A1 (A1a and A1b): new-onset plaque psoriasis to be treated with secukinumab

Experimental group

Description:

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).

Treatment:

Biological: Secukinumab

Arm B1 (B1a and B1b): new-onset plaque psoriasis to be treated with nb-UVB

Active Comparator group

Description:

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).

Treatment:

Radiation: nb-UVB

Drug: Betamethasone

Drug: Calcipotriol

Arm A2: new-onset plaque psoriasis to be treated with secukinumab

Experimental group

Description:

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).

Treatment:

Biological: Secukinumab

Arm C1: chronic plaque psoriasis to be treated with secukinumab

Experimental group

Description:

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).

Treatment:

Biological: Secukinumab

Arm C2: chronic plaque psoriasis to be treated with secukinumab

Experimental group

Description:

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).

Treatment:

Biological: Secukinumab