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

Phase 4

Terminated

• Conditions: Plaque Psoriasis; Psoriasis Vulgaris; Psoriasis
• Interventions: Biological: Brodalumab; Other: Placebo; Biological: Guselkumab

• Registration Number: NCT04533737
• Lead Sponsor: LEO Pharma

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2020-08-26
• Study First Submitted QC: 2020-08-26
• Study First Posted: 2020-09-01
• Study Start: 2020-12-17
• Primary Completion: 2022-09-08
• Study Completion: 2022-12-07
• Results First Submitted: 2023-09-07
• Results First Submitted QC: 2024-01-08
• Results First Posted: 2024-01-09
• Status Verified: 2024-02
• Last Update Submitted: 2025-02-21
• Last Update Posted: 2025-03-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 113

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1 (brodalumab + dummy 1)	Placebo	Participants receive: * Brodalumab 210 mg (1.5 ml) at Weeks 0, 1, 2, and then every 2 weeks. * Dummy 1 (placebo 1.0 ml) at Weeks 0, 4, and then every 8 weeks.
Arm 1 (brodalumab + dummy 1)	Brodalumab	Participants receive: * Brodalumab 210 mg (1.5 ml) at Weeks 0, 1, 2, and then every 2 weeks. * Dummy 1 (placebo 1.0 ml) at Weeks 0, 4, and then every 8 weeks.
Arm 2 (guselkumab + dummy 2)	Guselkumab	Participants receive: * Guselkumab 100 mg (1.0 ml) at Weeks 0, 4, and then every 8 weeks. * Dummy 2 (placebo 1.5 ml) at Weeks 0, 1, 2, and then every 2 weeks.
Arm 2 (guselkumab + dummy 2)	Placebo	Participants receive: * Guselkumab 100 mg (1.0 ml) at Weeks 0, 4, and then every 8 weeks. * Dummy 2 (placebo 1.5 ml) at Weeks 0, 1, 2, and then every 2 weeks.

Primary Outcome Measures

Name	Time	Method
Having Psoriasis Area and Severity Index (PASI) 100 Response at Week 16	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.

Secondary Outcome Measures

Name	Time	Method
Time to PASI 90 Response (Summarized as the Cumulative Incidence for Achieving PASI 90 at Each Timepoint, Stratified by Weight)	up to 28 weeks	Time to having 90% improvement from baseline in PASI score. The outcome measure summarizes the cumulative percentage of subjects with PASI 90 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.
Having IGA of 0 or 1, Assessed Separately at Weeks 16 and 28.	Weeks 16 and 28	Having a score of 0 (clear) or 1 (almost clear) in IGA. The outcome measure is summarized using the least squares mean percentage of subjects having an IGA score of 0 or 1 at Weeks 16 and 28, based on a logistic regression model adjusted for baseline body weight (\<=100 kg,\>100 kg) and baseline IGA score.; The IGA is an instrument used in clinical trials to rate the severity of psoriasis and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component Score From Baseline, Assessed Separately at Weeks 4, 8, 16, and 28.	Weeks 4, 8, 16, and 28	The SF-36v2 is a 36-item general health status assessment. Participants answer each question by selecting 1 of 3 to 6 categorical response options. The SF-36v2 yields scores for 8 health domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health) and 2 psychometrically derived summary scores (a physical component summary and a mental component summary). The mental component summary score ranges from -4.0 to 79.7. Higher scores indicate better outcome.
Time to PASI 100 Response (Summarized as the Cumulative Incidence for Achieving PASI 100 at Each Timepoint, Stratified by Weight)	up to 28 weeks	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.
Having Investigator's Global Assessment (IGA) of 0, Assessed Separately at Weeks 16 and 28.	Weeks 16 and 28	Having a score of 0 (clear) in IGA. The outcome measure is summarized using the least squares mean percentage of subjects having an IGA score of 0 at Weeks 16 and 28, based on a logistic regression model adjusted for baseline body weight (\<=100 kg,\>100 kg) and baseline IGA score.; The IGA is an instrument used in clinical trials to rate the severity of psoriasis and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Having Dermatology Life Quality Index (DLQI) Total Score of 0 or 1, Assessed Separately at Weeks 4, 8, 12, 16, 20, 24, and 28.	Weeks 4, 8, 12, 16, 20, 24, and 28	The outcome measure is summarized using the least squares mean percentage of subjects having a DLQI score of 0 or 1 at Weeks 4, 8, 12, 16, 20, 24, and 28, based on a logistic regression model adjusted for baseline body weight (\<=100 kg,\>100 kg) and baseline DLQI score.; The DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4-point Likert scale (0 = 'not at all/not relevant'; 1 = 'a little'; 2 = 'a lot'; 3 = 'very much'). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor quality of life.
Occurrence of Treatment-emergent Adverse Events (AEs) From Baseline to Week 28.	From baseline to Week 28	An adverse event is considered treatment-emergent if the onset occurred after the first administration of IMP or if the event started prior to the first administration of IMP and worsened in severity after the first administration of IMP.
Having PASI 100 Response, Assessed Separately at Weeks 4, 8, and 28.	Weeks 4, 8, and 28	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 Weeks 4, 8, and 28, 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.
Having PASI 90 Response, Assessed Separately at Weeks 4, 8, 16, and 28.	Weeks 4, 8, 16, and 28	Having 90% improvement from baseline in PASI score. The outcome measure is summarized using the least squares mean percentage of subjects having PASI 90 response at Weeks 4, 8, 16, and 28, 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 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.
Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Physical Component Score From Baseline, Assessed Separately at Weeks 4, 8, 16, and 28.	Weeks 4, 8, 16, and 28	The SF-36v2 is a 36-item general health status assessment. Participants answer each question by selecting 1 of 3 to 6 categorical response options. The SF-36v2 yields scores for 8 health domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health) and 2 psychometrically derived summary scores (a physical component summary and a mental component summary). The physical component summary score ranges from 5.1 to 79.7. Higher scores indicate better outcome.

Trial Locations

Locations (4)

LEO Pharma Investigational Site; 🇬🇧 London, United Kingdom

LEO Pharma investigational site; 🇬🇧 Leeds, West Yorkshire, United Kingdom

LEO Pharma Investigational Site 2; 🇬🇷 Thessaloníki, Greece

LEO Pharma Investigational Site 1; 🇬🇷 Thessaloníki, Greece