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

Psoriasis Clinical Trial

— COBRA  

Official title:

Efficacy and Safety Comparison of Brodalumab Versus Guselkumab in Adult Subjects With Moderate-to-severe Plaque Psoriasis and Inadequate Response to Ustekinumab

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04533737
• Other study ID #: LP0160-1510
• Secondary ID: 2019-004099-20U1
• Status: Terminated
• Phase: Phase 4
• Start date: December 17, 2020
• Est. completion date: December 7, 2022

Study information

• Verified date: February 2024
• Source: LEO Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 113
• Est. completion date: December 7, 2022
• Est. primary completion date: September 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Plaque Psoriasis
• Psoriasis
• Psoriasis Vulgaris

Intervention

Biological:
• Brodalumab
Pre-filled syringe with 210 mg brodalumab in 1.5 ml solution for subcutaneous injection

Other:
• Placebo
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

Biological:
• Guselkumab
Pre-filled syringe with 100 mg guselkumab in 1 ml solution for subcutaneous injection

Locations

Country	Name	City	State
Austria	LEO Pharma Investigational Site	Graz	Steiermark
Austria	LEO Pharma Investigational Site	Wien
Belgium	LEO Pharma Investigational Site	Brussels
Belgium	LEO Pharma Investigational Site	Herstal
Belgium	LEO Pharma Investigational Site	Namur
Denmark	LEO Pharma Investigational Site	Copenhagen
Denmark	LEO Pharma Investigational Site	Hellerup
Denmark	LEO Pharma Investigational Site	Roskilde
France	LEO Pharma Investigational Site	Antony
France	LEO Pharma Investigational Site	Marseille	Bouches-du-Rhône
France	LEO Pharma Investigational Site	Martigues	Bouches-du-Rhône
France	LEO Pharma Investigational Site	Nice
France	LEO Pharma Investigational Site	Rouen	Seine-Maritime 10
France	LEO Pharma Investigational Site	Saint-Mandé	Val-de-Marne
France	LEO Pharma Investigational Site	St Priest en Jarez cedex
France	LEO Pharma Investigational Site	Toulouse
Germany	LEO Pharma Investigational Site	Aachen
Germany	LEO Pharma Investigational Site	Augsburg
Germany	LEO Pharma Investigational Site	Bad Bentheim
Germany	LEO Pharma Investigational Site	Bonn
Germany	LEO Pharma Investigational Site	Bramsche
Germany	LEO Pharma Investigational Site	Buxtehude
Germany	LEO Pharma Investigational Site	Darmstadt
Germany	LEO Pharma Investigational Site	Erlangen
Germany	LEO Pharma Investigational Site	Frankfurt am Main
Germany	LEO Pharma Investigational Site	Freiburg im Breisgau	Baden-Wuerttemberg
Germany	LEO Pharma Investigational Site	Hamburg
Germany	LEO Pharma Investigational Site	Hamburg
Germany	LEO Pharma Investigational Site	Kiel
Germany	LEO Pharma Investigational Site	Köln
Germany	LEO Pharma Investigational Site	Mainz
Germany	LEO Pharma Investigational Site	Mainz
Germany	LEO Pharma Investigational Site	Memmingen
Germany	LEO Pharma Investigational Site	Munich
Germany	LEO Pharma Investigational Site	Münster
Germany	LEO Pharma Investigational Site	Selters
Greece	LEO Pharma Investigational Site 1	Athens
Greece	LEO Pharma Investigational Site 2	Athens
Greece	LEO Pharma Investigational Site	Thessaloniki
Greece	LEO Pharma Investigational Site 1	Thessaloníki
Greece	LEO Pharma Investigational Site 2	Thessaloníki
Italy	LEO Pharma Investigational Site	Napoli
Italy	LEO Pharma Investigational Site	Pisa
Italy	LEO Pharma Investigational Site	Roma
Italy	LEO Pharma Investigational Site	Rozzano
Netherlands	LEO Pharma Investigational Site	Almere	RL Almere
Netherlands	LEO Pharma Investigational Site	Amsterdam
Netherlands	LEO Pharma Investigational Site	Bergen Op Zoom	Bergen
Spain	LEO Pharma Investigational Site	Alicante
Spain	LEO Pharma Investigational Site	Barcelona
Spain	LEO Pharma Investigational Site	Barcelona
Spain	LEO Pharma Investigational Site	Bilbao	Vizcaya
Spain	LEO Pharma Investigational Site	Granada
Spain	LEO Pharma Investigational Site	Madrid
Spain	LEO Pharma Investigational Site	Madrid
Spain	LEO Pharma Investigational Site	Mieres	Asturias
Spain	LEO Pharma Investigational Site	Pontevedra
Spain	LEO Pharma Investigational Site	Valencia
Sweden	LEO Pharma Investigational Site	Solna	Stockholm
Switzerland	LEO Pharma Investigational Site	Saint Gallen
Switzerland	LEO Pharma Investigational Site	Zürich
United Kingdom	LEO Pharma Investigational Site	Bath	Avon
United Kingdom	LEO Pharma Investigational Site	Dudley	West Midlands
United Kingdom	LEO Pharma investigational site	Leeds	West Yorkshire
United Kingdom	LEO Pharma Investigational Site	London

Sponsors (1)

Lead Sponsor	Collaborator
LEO Pharma

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  France,  Germany,  Greece,  Italy,  Netherlands,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (1)

Reich K, Bianchi L, Khemis A, Maul JT, Tsianakas A, Schempp CM, Petersen K, Noergaard MM, Puig L. Brodalumab Versus Guselkumab in Patients with Moderate-to-Severe Psoriasis with an Inadequate Response to Ustekinumab: A Randomized, Multicenter, Double-Blin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 16
Secondary	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.	up to 28 weeks
Secondary	Time to PASI 90 Response (Summarized as the Cumulative Incidence for Achieving PASI 90 at Each Timepoint, Stratified by Weight)	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.	up to 28 weeks
Secondary	Having PASI 100 Response, Assessed Separately at 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.	Weeks 4, 8, and 28
Secondary	Having PASI 90 Response, Assessed Separately at 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.	Weeks 4, 8, 16, and 28
Secondary	Having Investigator's Global Assessment (IGA) of 0, Assessed Separately at 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).	Weeks 16 and 28
Secondary	Having IGA of 0 or 1, Assessed Separately at 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).	Weeks 16 and 28
Secondary	Having Dermatology Life Quality Index (DLQI) Total Score of 0 or 1, Assessed Separately at 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.	Weeks 4, 8, 12, 16, 20, 24, and 28
Secondary	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.	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.	Weeks 4, 8, 16, and 28
Secondary	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.	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.	Weeks 4, 8, 16, and 28
Secondary	Occurrence of Treatment-emergent Adverse Events (AEs) 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.	From baseline to Week 28