Clinical trial NCT04533737: Efficacy and Safety of Brodalumab Compared With Guselkumab in the Treatment of Plaque Psoriasis After Inadequate Response to Ustekinumab
Official title: Efficacy and Safety Comparison of Brodalumab Versus Guselkumab in Adult Subjects With Moderate-to-severe Plaque Psoriasis and Inadequate Response to Ustekinumab
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Plaque Psoriasis
Psoriasis Vulgaris
Psoriasis
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2020-09-01
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Having Psoriasis Area and Severity Index (PASI) 100 Response at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Time to PASI 100 Response (Summarized as the Cumulative Incidence for Achieving PASI 100 at Each Timepoint, Stratified by Weight)
timeFrame: up to 28 weeks
measure: Time to PASI 90 Response (Summarized as the Cumulative Incidence for Achieving PASI 90 at Each Timepoint, Stratified by Weight)
timeFrame: up to 28 weeks
measure: Having PASI 100 Response, Assessed Separately at Weeks 4, 8, and 28.
timeFrame: Weeks 4, 8, and 28
measure: Having PASI 90 Response, Assessed Separately at Weeks 4, 8, 16, and 28.
timeFrame: Weeks 4, 8, 16, and 28
measure: Having Investigator's Global Assessment (IGA) of 0, Assessed Separately at Weeks 16 and 28.
timeFrame: Weeks 16 and 28
measure: Having IGA of 0 or 1, Assessed Separately at Weeks 16 and 28.
timeFrame: Weeks 16 and 28
measure: Having Dermatology Life Quality Index (DLQI) Total Score of 0 or 1, Assessed Separately at Weeks 4, 8, 12, 16, 20, 24, and 28.
timeFrame: Weeks 4, 8, 12, 16, 20, 24, and 28
measure: 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.
timeFrame: Weeks 4, 8, 16, and 28
measure: 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.
timeFrame: Weeks 4, 8, 16, and 28
measure: Occurrence of Treatment-emergent Adverse Events (AEs) From Baseline to Week 28.
timeFrame: From baseline to Week 28
Other outcomes:
Locations:
city: Graz
country: Austria
facility: LEO Pharma Investigational Site
state: Steiermark
city: Wien
country: Austria
facility: LEO Pharma Investigational Site
city: Brussels
country: Belgium
facility: LEO Pharma Investigational Site
city: Herstal
country: Belgium
facility: LEO Pharma Investigational Site
city: Namur
country: Belgium
facility: LEO Pharma Investigational Site
city: Copenhagen
country: Denmark
facility: LEO Pharma Investigational Site
city: Hellerup
country: Denmark
facility: LEO Pharma Investigational Site
city: Roskilde
country: Denmark
facility: LEO Pharma Investigational Site
city: Marseille
country: France
facility: LEO Pharma Investigational Site
state: Bouches-du-Rhône
city: Martigues
country: France
facility: LEO Pharma Investigational Site
state: Bouches-du-Rhône
city: Rouen
country: France
facility: LEO Pharma Investigational Site
state: Seine-Maritime 10
city: Saint-Mandé
country: France
facility: LEO Pharma Investigational Site
state: Val-de-Marne
city: Antony
country: France
facility: LEO Pharma Investigational Site
city: Nice
country: France
facility: LEO Pharma Investigational Site
city: St Priest en Jarez cedex
country: France
facility: LEO Pharma Investigational Site
city: Toulouse
country: France
facility: LEO Pharma Investigational Site
city: Freiburg im Breisgau
country: Germany
facility: LEO Pharma Investigational Site
state: Baden-Wuerttemberg
city: Aachen
country: Germany
facility: LEO Pharma Investigational Site
city: Augsburg
country: Germany
facility: LEO Pharma Investigational Site
city: Bad Bentheim
country: Germany
facility: LEO Pharma Investigational Site
city: Bonn
country: Germany
facility: LEO Pharma Investigational Site
city: Bramsche
country: Germany
facility: LEO Pharma Investigational Site
city: Buxtehude
country: Germany
facility: LEO Pharma Investigational Site
city: Darmstadt
country: Germany
facility: LEO Pharma Investigational Site
city: Erlangen
country: Germany
facility: LEO Pharma Investigational Site
city: Frankfurt am Main
country: Germany
facility: LEO Pharma Investigational Site
city: Hamburg
country: Germany
facility: LEO Pharma Investigational Site
city: Hamburg
country: Germany
facility: LEO Pharma Investigational Site
city: Kiel
country: Germany
facility: LEO Pharma Investigational Site
city: Köln
country: Germany
facility: LEO Pharma Investigational Site
city: Mainz
country: Germany
facility: LEO Pharma Investigational Site
city: Mainz
country: Germany
facility: LEO Pharma Investigational Site
city: Memmingen
country: Germany
facility: LEO Pharma Investigational Site
city: Munich
country: Germany
facility: LEO Pharma Investigational Site
city: Münster
country: Germany
facility: LEO Pharma Investigational Site
city: Selters
country: Germany
facility: LEO Pharma Investigational Site
city: Athens
country: Greece
facility: LEO Pharma Investigational Site 1
city: Athens
country: Greece
facility: LEO Pharma Investigational Site 2
city: Thessaloniki
country: Greece
facility: LEO Pharma Investigational Site
city: Thessaloníki
country: Greece
facility: LEO Pharma Investigational Site 1
city: Thessaloníki
country: Greece
facility: LEO Pharma Investigational Site 2
city: Napoli
country: Italy
facility: LEO Pharma Investigational Site
city: Pisa
country: Italy
facility: LEO Pharma Investigational Site
city: Roma
country: Italy
facility: LEO Pharma Investigational Site
city: Rozzano
country: Italy
facility: LEO Pharma Investigational Site
city: Bergen Op Zoom
country: Netherlands
facility: LEO Pharma Investigational Site
state: Bergen
city: Almere
country: Netherlands
facility: LEO Pharma Investigational Site
state: RL Almere
city: Amsterdam
country: Netherlands
facility: LEO Pharma Investigational Site
city: Mieres
country: Spain
facility: LEO Pharma Investigational Site
state: Asturias
city: Bilbao
country: Spain
facility: LEO Pharma Investigational Site
state: Vizcaya
city: Alicante
country: Spain
facility: LEO Pharma Investigational Site
city: Barcelona
country: Spain
facility: LEO Pharma Investigational Site
city: Barcelona
country: Spain
facility: LEO Pharma Investigational Site
city: Granada
country: Spain
facility: LEO Pharma Investigational Site
city: Madrid
country: Spain
facility: LEO Pharma Investigational Site
city: Madrid
country: Spain
facility: LEO Pharma Investigational Site
city: Pontevedra
country: Spain
facility: LEO Pharma Investigational Site
city: Valencia
country: Spain
facility: LEO Pharma Investigational Site
city: Solna
country: Sweden
facility: LEO Pharma Investigational Site
state: Stockholm
city: Saint Gallen
country: Switzerland
facility: LEO Pharma Investigational Site
city: Zürich
country: Switzerland
facility: LEO Pharma Investigational Site
city: Bath
country: United Kingdom
facility: LEO Pharma Investigational Site
state: Avon
city: Dudley
country: United Kingdom
facility: LEO Pharma Investigational Site
state: West Midlands
city: Leeds
country: United Kingdom
facility: LEO Pharma investigational site
state: West Yorkshire
city: London
country: United Kingdom
facility: LEO Pharma Investigational Site
Study officials:
affiliation: LEO Pharma
name: Medical Expert
role: STUDY_DIRECTOR
References:
citation: 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.