Efficacy and Safety of Brodalumab Compared With Guselkumab in the Treatment of Plaque Psoriasis After Inadequate Response to Ustekinumab

Phase 4TerminatedNCT04533737

LEO Pharma113 enrolled

Overview

The trial investigates the efficacy and safety of brodalumab against guselkumab in treatment for patients with moderate-to-severe plaque psoriasis who still have some remaining symptoms after ustekinumab treatment.

Brodalumab is an anti-interleukin 17 receptor A antibody (IL-17RA) and blocks the inflammatory effects of different IL-17 cytokines (IL-17A, IL-17C, IL-17F, IL-17A/F heterodimer, and IL-17E) in the skin. With increasing availability of novel biologics with new targets, the complexity of choosing the appropriate biologic treatment is ever more challenging for physicians. Therefore, the primary objective of this trial is to compare the efficacy of brodalumab versus guselkumab in adult participants with moderate to severe plaque psoriasis and inadequate response to ustekinumab, thereby providing new scientific information that could support decision making in the clinical setting. The study will run approximately 32 weeks for each participant (including a 2- to 4-weeks screening period and a 28-week treatment period), with the primary endpoint measurement at Week 16. Participants receive subcutaneous injections of brodalumab or guselkumab. Dummy injections are also given, so participants and assessors are unaware of which treatment is given.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

113

Conditions

Plaque Psoriasis Psoriasis Vulgaris Psoriasis

Interventions

BrodalumabBIOLOGICAL

Pre-filled syringe with 210 mg brodalumab in 1.5 ml solution for subcutaneous injection

PlaceboOTHER

The placebo solution is similar to the active guselkumab (Dummy 1) or brodalumab (Dummy 2) solution except that it does not contain any active substance

GuselkumabBIOLOGICAL

Pre-filled syringe with 100 mg guselkumab in 1 ml solution for subcutaneous injection

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Participant has a diagnosis of plaque psoriasis for at least 6 months before the first administration of investigational medicinal product (IMP) as determined by the investigator. * Participant has inadequately controlled plaque psoriasis currently treated with ustekinumab, and fulfils ALL of the following criteria: 1. Ustekinumab administered at least 3 times at or higher than the approved dose or frequency before randomisation. 2. IGA ≥2 at screening and baseline. 3. Absolute PASI \>3 at screening and baseline. * Participant has no evidence of active tuberculosis according to local standard of care for patients requiring initiation of a biologic treatment. Participants with adequately treated latent tuberculosis, according to local guidelines, are eligible. Key Exclusion Criteria: * Participant was diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, or other skin conditions (e.g. eczema) that would interfere with evaluations of the effect of IMP on plaque psoriasis. * Participant has clinically important active infections or infestations, chronic, recurrent, or latent infections or infestations, or is immunocompromised (e.g. human immunodeficiency virus). * Participant has any systemic disease (e.g. renal failure, heart failure, hypertension, liver disease, diabetes, anaemia) considered by the investigator to be clinically significant and uncontrolled. * Participant has a known history of Crohn's disease. * Participant has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma. * Participant has a history of malignancy within 5 years, except for treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma. * Participant has a known history of active tuberculosis. * Participant has a history of suicidal behaviour (i.e. 'actual suicide attempt', 'interrupted attempt', 'aborted attempt', or 'preparatory acts or behaviour') based on the Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire at screening or baseline. * Participant has any suicidal ideation of severity 4 or 5 ('some intent to act, no plan' or 'specific plan and intent') based on the C-SSRS questionnaire at screening or baseline. * Participant has a Patient Health Questionnaire-8 (PHQ-8) score of ≥10, corresponding to moderate to severe depression at screening or baseline. * Participant has previously been treated with any anti-interleukin (IL)-17A, anti-IL 17 receptor subunit A, or anti-IL-23 besides ustekinumab. * Participant has known or suspected hypersensitivity to any component(s) of the IMPs.

Locations (65)

Outcomes

Primary Outcomes

Having Psoriasis Area and Severity Index (PASI) 100 Response at Week 16

Having 100% improvement from baseline in PASI score. The outcome measure is summarized using the least squares mean percentage of subjects having PASI 100 response at Week 16, based on a logistic regression model adjusted for baseline body weight (\<=100 kg,\>100 kg) and baseline PASI score. The PASI is the most widely used tool in clinical practice and clinical trials to assess psoriasis severity and extent. Assessment is done based on the condition of the disease at the time of evaluation, not in relation to the condition at a previous visit. The investigator assesses the severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions (head/neck, trunk, upper extremities, lower extremities) according to a severity scale. The investigator also assesses the extent of psoriasis within each of the 4 body regions. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe/extensive condition.

Time frame: Week 16

Secondary Outcomes

Time to PASI 100 Response (Summarized as the Cumulative Incidence for Achieving PASI 100 at Each Timepoint, Stratified by Weight)

Time to having 100% improvement from baseline in PASI score. The outcome measure summarizes the cumulative percentage of subjects with PASI 100 response (stratified by weight) over time, based on the Aalen-Johansen estimator. The PASI is the most widely used tool in clinical practice and clinical trials to assess psoriasis severity and extent. Assessment is done based on the condition of the disease at the time of evaluation, not in relation to the condition at a previous visit. The investigator assesses the severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions (head/neck, trunk, upper extremities, lower extremities) according to a severity scale. The investigator also assesses the extent of psoriasis within each of the 4 body regions. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe/extensive condition.

Time frame: up to 28 weeks

Time to PASI 90 Response (Summarized as the Cumulative Incidence for Achieving PASI 90 at Each Timepoint, Stratified by Weight)

Data from ClinicalTrials.gov

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