Clinical trial NCT04306315: Adjusted Brodalumab Dose Compared With Standard Brodalumab Dose in Subjects With Moderate-to-severe Plaque Psoriasis and ≥120 kg Body Weight
Official title: Adjustable Brodalumab Dosage Regimen Compared With Standard Brodalumab Treatment for 52 Weeks in Subjects With Moderate-to-severe Plaque Psoriasis and ≥120 kg Body Weight
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Psoriasis Vulgaris
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2020-03-12
Enrollment: 385
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study investigates if an adjusted brodalumab dosage regimen will give improved efficacy in psoriasis in patients with a body weight of over 120 kg. The increased dosage regimen will be compared to the standard brodalumab treatment plus placebo.

Detailed description: Brodalumab is an anti-IL-17 receptor antibody and blocks the inflammatory effects of IL-17 in the skin. Some psoriasis patients with a higher body weight experienced a lower treatment effect of brodalumab in clinical studies. Therefore, the purpose of this study is to investigate if increasing the dose of brodalumab will increase the effect of treatment for patients with a higher body weight. The study will run over 60-62 weeks, including screening, treatment period and safety follow-up, with the primary endpoint measurement at Week 40. Patients will receive subcutaneous injections of brodalumab at Week 0, 1, and 2, followed by injections every 2 weeks. Participants not fulfilling a predefined response at any time after Week 16 will receive a dose adjustment to 280 mg brodalumab or 210 mg brodalumab plus placebo every 2 weeks.

Eligibility criteria: Key Inclusion Criteria:

* Signed and dated informed consent has been obtained prior to any protocol-related procedures.
* Age ≥18 to \<75 years at the time of screening.
* Diagnosed with chronic plaque psoriasis at least 6 months before randomisation.
* Body weight ≥120 kg at the time of screening.
* Moderate-to-severe plaque psoriasis as defined by: BSA ≥10% and PASI ≥12 at screening and baseline.
* No evidence of active or latent tuberculosis according to local standard of care.

Key Exclusion Criteria:

* 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 the investigational medicinal product (IMP) on participants with plaque psoriasis.
* Clinically important active infections or infestations, chronic, recurrent or latent infections or infestations, or is immunocompromised (e.g., human immunodeficiency virus, hepatitis B, and hepatitis C).
* Any systemic disease considered by the investigator to be uncontrolled and either immunocompromising the participants and/or placing the participant at undue risk of intercurrent diseases (including, but not limited to, renal failure, heart failure, liver disease, diabetes, and anaemia).
* History of Crohn's disease.
* Myocardial infarction or stroke, or unstable angina pectoris within the past 12 months.
* Any active malignancy.
* 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.
* 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 at baseline.
* Any suicidal ideation of category 4 or 5 ('active suicidal ideation with some intent to act, without specific plan' or ' active suicidal ideation with specific plan and intent') based on the C-SSRS questionnaire at screening or at baseline.
* A Patient Health Questionnaire (PHQ)-8 score of ≥10 corresponding to moderate-to-severe depression at screening or at baseline.

Primary outcomes:
measure: Having at least 90% lower Psoriasis Area and Severity Index (PASI) score relative to baseline (PASI 90 response) at Week 40.
timeFrame: Week 40
Secondary outcomes:
measure: Having static Physician's Global Assessment (sPGA) score of 0 or 1 at Week 40
timeFrame: Week 40
measure: Having PASI 90 response at Week 52
timeFrame: Week 52
measure: Having sPGA score of 0 or 1 at Week 52
timeFrame: Week 52
measure: Having sPGA of genitalia (sPGA-G) score of 0 or 1 at both Week 40 and Week 52
timeFrame: Week 40
measure: Having sPGA of genitalia (sPGA-G) score of 0 or 1 at Week 40
timeFrame: Week 40
measure: Having sPGA-G score of 0 or 1 at Week 52
timeFrame: Week 52
measure: Having PASI 100 response at Week 40
timeFrame: Week 40
measure: Having PASI 100 response at Week 52
timeFrame: Week 52
measure: Change from baseline at Weeks 40 and 52 in PASI score
timeFrame: Week 40 and 52
measure: Change from baseline at Weeks 40 and 52 in affected body surface area (BSA)
timeFrame: Week 40 and 52
measure: Having Dermatology Life Quality Index (DLQI) total score of 0 or 1 at Week 40
timeFrame: Week 40
measure: Having DLQI total score of 0 or 1 at Week 52
timeFrame: Week 52
measure: Change from baseline at Weeks 40 and 52 in DLQI total score
timeFrame: Week 40 and 52
measure: Number of Participants Experiencing Adverse Events (AEs) up to Week 58.
timeFrame: Week 58
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: LEO Pharma Investigational Site
city: Ham-sur-Heure-Nalinnes
country: Belgium
facility: LEO Pharma Investigational Site
city: Leuven
country: Belgium
facility: LEO Pharma Investigational Site
city: Liège
country: Belgium
facility: LEO Pharma Investigational Site
city: Kutná Hora
country: Czechia
facility: LEO Pharma Investigational Site
city: Nový Jičín
country: Czechia
facility: LEO Pharma Investigational Site
city: Plzen-Bory
country: Czechia
facility: LEO Pharma Investigational Site
city: Amiens
country: France
facility: LEO Pharma Investigational Site
state: Somme
city: Saint-Priest-en-Jarez
country: France
facility: LEO Pharma Investigational Site
city: Toulouse cedex 9
country: France
facility: LEO Pharma Investigational Site
city: Valence
country: France
facility: LEO Pharma Investigational Site
city: Langenau
country: Germany
facility: LEO Pharma Investigational Site
state: Baden-Wuerttemberg
city: Berlin
country: Germany
facility: LEO Pharma Investigational Site
state: Berline
city: Limburg
country: Germany
facility: LEO Pharma Investigational Site
state: Hessen
city: Wiesbaden
country: Germany
facility: LEO Pharma Investigational Site
state: Hessen
city: Lohne
country: Germany
facility: LEO Pharma Investigational Site
state: Lower Saxony
city: Mainz
country: Germany
facility: LEO Pharma Investigational Site
state: Rheinland-Pfalz
city: Kiel
country: Germany
facility: LEO Pharma Investigational Site
state: Schleswig-Holstein
city: Bad Bentheim
country: Germany
facility: LEO Pharma Investigational Site
city: Bielefeld
country: Germany
facility: LEO Pharma Investigational Site
city: Hamburg
country: Germany
facility: LEO Pharma Investigational Site
city: Memmingen
country: Germany
facility: LEO Pharma Investigational Site
city: Münster
country: Germany
facility: LEO Pharma Investigational Site
city: Oldenburg
country: Germany
facility: LEO Pharma Investigational Site
city: Osnabrück
country: Germany
facility: LEO Pharma Investigational Site
city: Heraklion
country: Greece
facility: LEO Pharma Investigational Site
state: Crete
city: Athens
country: Greece
facility: LEO Pharma Investigational Site
city: Athens
country: Greece
facility: LEO Pharma Investigational Site
city: Piraeus
country: Greece
facility: LEO Pharma Investigational Site
city: Thessaloníki
country: Greece
facility: LEO Pharma Investigational Site
city: Thessaloníki
country: Greece
facility: LEO Pharma Investigational Site
city: Thessaloníki
country: Greece
facility: LEO Pharma Investigational Site
city: Debrecen
country: Hungary
facility: LEO Pharma Investigational Site
city: Orosháza
country: Hungary
facility: LEO Pharma Investigational Site
city: Szolnok
country: Hungary
facility: LEO Pharma Investigational Site
city: Veszprém
country: Hungary
facility: LEO Pharma Investigational Site
city: Ancona
country: Italy
facility: LEO Pharma Investigational Site
city: Bologna
country: Italy
facility: LEO Pharma Investigational Site
city: Brescia
country: Italy
facility: LEO Pharma Investigational Site
city: Coppito
country: Italy
facility: LEO Pharma Investigational Site
city: Modena
country: Italy
facility: LEO Pharma Investigational Site
city: Napoli
country: Italy
facility: LEO Pharma Investigational Site
city: Parma
country: Italy
facility: LEO Pharma Investigational Site
city: Pavia
country: Italy
facility: LEO Pharma Investigational Site
city: Roma
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: Beek
country: Netherlands
facility: LEO Pharma Investigational Site
city: Iwonicz-Zdrój
country: Poland
facility: LEO Pharma Investigational Site
city: Lublin
country: Poland
facility: LEO Pharma Investigational Site
city: Lublin
country: Poland
facility: LEO Pharma Investigational Site
city: Poznań
country: Poland
facility: LEO Pharma Investigational Site
city: Skierniewice
country: Poland
facility: LEO Pharma Investigational Site
city: Warszawa
country: Poland
facility: LEO Pharma Investigational Site
city: Warszawa
country: Poland
facility: LEO Pharma Investigational Site
city: Warszawa
country: Poland
facility: LEO Pharma Investigational Site
city: Wrocław
country: Poland
facility: LEO Pharma Investigational Site
city: Wrocław
country: Poland
facility: LEO Pharma Investigational Site
city: Wrocław
country: Poland
facility: LEO Pharma Investigational Site
city: Łódź
country: Poland
facility: LEO Pharma Investigational Site
city: Łódź
country: Poland
facility: LEO Pharma Investigational Site
city: Alicante
country: Spain
facility: LEO Pharma Investigational Site
city: Badalona
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: Manises
country: Spain
facility: LEO Pharma Investigational Site
city: Pontevedra
country: Spain
facility: LEO Pharma Investigational Site
city: Pozuelo De Alarcón
country: Spain
facility: LEO Pharma Investigational Site
city: Santiago De Compostela
country: Spain
facility: LEO Pharma Investigational Site
city: Valencia
country: Spain
facility: LEO Pharma Investigational Site
city: Villajoyosa
country: Spain
facility: LEO Pharma Investigational Site
city: Chorley
country: United Kingdom
facility: LEO Pharma Investigational Site
city: Corby
country: United Kingdom
facility: LEO Pharma Investigational Site
city: Corby
country: United Kingdom
facility: LEO Pharma Investigational Site
city: Coventry
country: United Kingdom
facility: LEO Pharma Investigational Site
city: Liverpool
country: United Kingdom
facility: LEO Pharma Investigational Site
city: London
country: United Kingdom
facility: LEO Pharma Investigational Site
city: London
country: United Kingdom
facility: LEO Pharma Investigational Site
city: Northwood
country: United Kingdom
facility: LEO Pharma Investigational Site
city: Shipley
country: United Kingdom
facility: LEO Pharma Investigational Site
Study officials:
affiliation: LEO Pharma
name: Medical Expert
role: STUDY_DIRECTOR
References: