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

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

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.

Study Overview

• Status: Terminated
• Conditions: Psoriasis; Plaque Psoriasis; Psoriasis Vulgaris
• Intervention / Treatment: Biological: Brodalumab; Biological: Guselkumab; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • LEO Pharma Investigational Site
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • LEO Pharma Investigational Site
• Belgium
  • Brussels, Belgium, 1200
    • LEO Pharma Investigational Site
  • Herstal, Belgium, 4040
    • LEO Pharma Investigational Site
  • Namur, Belgium, 5000
    • LEO Pharma Investigational Site
• Denmark
  • Copenhagen, Denmark, 2400
    • LEO Pharma Investigational Site
  • Hellerup, Denmark, 2900
    • LEO Pharma Investigational Site
  • Roskilde, Denmark, 4000
    • LEO Pharma Investigational Site
• France
  • Antony, France, 92160
    • LEO Pharma Investigational Site
  • Nice, France, 06000
    • LEO Pharma Investigational Site
  • St Priest en Jarez cedex, France, 42277
    • LEO Pharma Investigational Site
  • Toulouse, France, 31059
    • LEO Pharma Investigational Site
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13008
      • LEO Pharma Investigational Site
    • Martigues, Bouches-du-Rhône, France, 13500
      • LEO Pharma Investigational Site
  • Seine-Maritime 10
    • Rouen, Seine-Maritime 10, France, 76031
      • LEO Pharma Investigational Site
  • Val-de-Marne
    • Saint-Mandé, Val-de-Marne, France, 94160
      • LEO Pharma Investigational Site
• Germany
  • Aachen, Germany, 52074
    • LEO Pharma Investigational Site
  • Augsburg, Germany, 86163
    • LEO Pharma Investigational Site
  • Bad Bentheim, Germany, 48455
    • LEO Pharma Investigational Site
  • Bonn, Germany, 53127
    • LEO Pharma Investigational Site
  • Bramsche, Germany, 49565
    • LEO Pharma Investigational Site
  • Buxtehude, Germany, 21614
    • LEO Pharma Investigational Site
  • Darmstadt, Germany, 64297
    • LEO Pharma Investigational Site
  • Erlangen, Germany, 91054
    • LEO Pharma Investigational Site
  • Frankfurt am Main, Germany, 60590
    • LEO Pharma Investigational Site
  • Hamburg, Germany, 20537
    • LEO Pharma Investigational Site
  • Hamburg, Germany, 20246
    • LEO Pharma Investigational Site
  • Kiel, Germany, 24105
    • LEO Pharma Investigational Site
  • Köln, Germany, 50937
    • LEO Pharma Investigational Site
  • Mainz, Germany, 55128
    • LEO Pharma Investigational Site
  • Mainz, Germany, 55131
    • LEO Pharma Investigational Site
  • Memmingen, Germany, 87700
    • LEO Pharma Investigational Site
  • Munich, Germany, 80802
    • LEO Pharma Investigational Site
  • Münster, Germany, 48149
    • LEO Pharma Investigational Site
  • Selters, Germany, 56242
    • LEO Pharma Investigational Site
  • Baden-Wuerttemberg
    • Freiburg im Breisgau, Baden-Wuerttemberg, Germany, 79104
      • LEO Pharma Investigational Site
• Greece
  • Athens, Greece, 16121
    • LEO Pharma Investigational Site 1
  • Athens, Greece, 16121
    • LEO Pharma Investigational Site 2
  • Thessaloniki, Greece, 54643
    • LEO Pharma Investigational Site
  • Thessaloníki, Greece, 54643
    • LEO Pharma Investigational Site 1
  • Thessaloníki, Greece, 54643
    • LEO Pharma Investigational Site 2
• Italy
  • Napoli, Italy, 80121
    • LEO Pharma Investigational Site
  • Pisa, Italy, 56126
    • LEO Pharma Investigational Site
  • Roma, Italy, 00133
    • LEO Pharma Investigational Site
  • Rozzano, Italy, 20089
    • LEO Pharma Investigational Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • LEO Pharma Investigational Site
  • Bergen
    • Bergen Op Zoom, Bergen, Netherlands, 4614 VT
      • LEO Pharma Investigational Site
  • RL Almere
    • Almere, RL Almere, Netherlands, 1311
      • LEO Pharma Investigational Site
• Spain
  • Alicante, Spain, 03010
    • LEO Pharma Investigational Site
  • Barcelona, Spain, 08036
    • LEO Pharma Investigational Site
  • Barcelona, Spain, 08041
    • LEO Pharma Investigational Site
  • Granada, Spain, 18016
    • LEO Pharma Investigational Site
  • Madrid, Spain, 28031
    • LEO Pharma Investigational Site
  • Madrid, Spain, 28041
    • LEO Pharma Investigational Site
  • Pontevedra, Spain, 36001
    • LEO Pharma Investigational Site
  • Valencia, Spain, 46026
    • LEO Pharma Investigational Site
  • Asturias
    • Mieres, Asturias, Spain, 33611
      • LEO Pharma Investigational Site
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • LEO Pharma Investigational Site
• Sweden
  • Stockholm
    • Solna, Stockholm, Sweden, 171 76
      • LEO Pharma Investigational Site
• Switzerland
  • Saint Gallen, Switzerland, 9007
    • LEO Pharma Investigational Site
  • Zürich, Switzerland, 8091
    • LEO Pharma Investigational Site
• United Kingdom
  • London, United Kingdom, SW17 0RE
    • LEO Pharma Investigational Site
  • Avon
    • Bath, Avon, United Kingdom, BA1 3NG
      • LEO Pharma Investigational Site
  • West Midlands
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • LEO Pharma Investigational Site
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS7 4SA
      • LEO Pharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 (brodalumab + dummy 1); 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.	Biological: Brodalumab; Pre-filled syringe with 210 mg brodalumab in 1.5 ml solution for subcutaneous injection; Other Names: Kyntheum®; 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; Other Names: Dummy 1/Dummy 2
Active Comparator: Arm 2 (guselkumab + dummy 2); 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.	Biological: Guselkumab; Pre-filled syringe with 100 mg guselkumab in 1 ml solution for subcutaneous injection; Other Names: Tremfya®; 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; Other Names: Dummy 1/Dummy 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: LEO Pharma
• Investigators: Study Director: Medical Expert, LEO Pharma

Publications and helpful links

General Publications

• 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-Blind Phase 4 Trial (COBRA). Dermatol Ther (Heidelb). 2024 Feb;14(2):453-468. doi: 10.1007/s13555-023-01092-x. Epub 2024 Feb 1.

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2020
• Primary Completion (Actual): September 8, 2022
• Study Completion (Actual): December 7, 2022

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): September 1, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases, Papulosquamous; Skin Diseases; Psoriasis; Dermatologic Agents; Brodalumab
• Other Study ID Numbers: LP0160-1510; 2019-004099-20 (EudraCT Number); U1111-1283-7584 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified IPD can be made available to researchers in a closed environment for a specified period of time.
• IPD Sharing Time Frame: Data is available to request after results of the trial are available on leopharmatrials.com
• IPD Sharing Access Criteria: De-identified Individual Participant Data can be made available to researchers and is subject to approved scientifically sound research proposal and signed data-sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes