Adjusted Brodalumab Dose Compared With Standard Brodalumab Dose in Subjects With Moderate-to-severe Plaque Psoriasis and ≥120 kg Body Weight (ADJUST)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Psoriasis Vulgaris
• Intervention / Treatment: Biological: Brodalumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 384
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Clincal Disclosure; Phone Number: (+1) 877-557-1168; Email: disclosure@leo-pharma.com

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Recruiting
    • LEO Pharma Investigational Site
  • Ham-sur-Heure-Nalinnes, Belgium, 6120
    • Recruiting
    • LEO Pharma Investigational Site
  • Leuven, Belgium, 3000
    • Recruiting
    • LEO Pharma Investigational Site
  • Liège, Belgium, B-4000
    • Recruiting
    • LEO Pharma Investigational Site
• Czechia
  • Kutná Hora, Czechia, 284 01
    • Recruiting
    • LEO Pharma Investigational Site
  • Nový Jičín, Czechia, 741 01
    • Recruiting
    • LEO Pharma Investigational Site
  • Plzen-Bory, Czechia, 305 99
    • Recruiting
    • LEO Pharma Investigational Site
• France
  • Saint-Priest-en-Jarez, France, 42270
    • Recruiting
    • LEO Pharma Investigational Site
  • Toulouse cedex 9, France, 31059
    • Recruiting
    • LEO Pharma Investigational Site
  • Valence, France, 13616
    • Recruiting
    • LEO Pharma Investigational Site
  • Somme
    • Amiens, Somme, France, 80054
      • Recruiting
      • LEO Pharma Investigational Site
• Germany
  • Bad Bentheim, Germany, 48455
    • Recruiting
    • LEO Pharma Investigational Site
  • Bielefeld, Germany, 33647
    • Recruiting
    • LEO Pharma Investigational Site
  • Hamburg, Germany, 20246
    • Recruiting
    • LEO Pharma Investigational Site
  • Memmingen, Germany, 87700
    • Recruiting
    • LEO Pharma Investigational Site
  • Münster, Germany, 48149
    • Recruiting
    • LEO Pharma Investigational Site
  • Oldenburg, Germany, 26133
    • Recruiting
    • LEO Pharma Investigational Site
  • Osnabrück, Germany, 49074
    • Recruiting
    • LEO Pharma Investigational Site
  • Baden-Wuerttemberg
    • Langenau, Baden-Wuerttemberg, Germany, 89129
      • Recruiting
      • LEO Pharma Investigational Site
  • Berline
    • Berlin, Berline, Germany, 10117
      • Recruiting
      • LEO Pharma Investigational Site
  • Hessen
    • Limburg, Hessen, Germany, 56242
      • Recruiting
      • LEO Pharma Investigational Site
    • Wiesbaden, Hessen, Germany, 65189
      • Recruiting
      • LEO Pharma Investigational Site
  • Lower Saxony
    • Lohne, Lower Saxony, Germany, 49393
      • Recruiting
      • LEO Pharma Investigational Site
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55128
      • Recruiting
      • LEO Pharma Investigational Site
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Recruiting
      • LEO Pharma Investigational Site
• Greece
  • Athens, Greece, 16121
    • Recruiting
    • LEO Pharma Investigational Site
  • Athens, Greece, 115 25
    • Recruiting
    • LEO Pharma Investigational Site
  • Piraeus, Greece, 185 36
    • Recruiting
    • LEO Pharma Investigational Site
  • Thessaloníki, Greece, 546 43
    • Recruiting
    • LEO Pharma Investigational Site
  • Thessaloníki, Greece, 56403
    • Recruiting
    • LEO Pharma Investigational Site
  • Thessaloníki, Greece, 54643
    • Recruiting
    • LEO Pharma Investigational Site
  • Crete
    • Heraklion, Crete, Greece, 711 10
      • Recruiting
      • LEO Pharma Investigational Site
• Hungary
  • Debrecen, Hungary, 4032
    • Recruiting
    • LEO Pharma Investigational Site
  • Orosháza, Hungary, 5900
    • Recruiting
    • LEO Pharma Investigational Site
  • Szolnok, Hungary, 5000
    • Recruiting
    • LEO Pharma Investigational Site
  • Veszprém, Hungary, 8200
    • Recruiting
    • LEO Pharma Investigational Site
• Italy
  • Ancona, Italy, 60020
    • Recruiting
    • LEO Pharma Investigational Site
  • Bologna, Italy, 40138
    • Recruiting
    • LEO Pharma Investigational Site
  • Brescia, Italy, 25123
    • Recruiting
    • LEO Pharma Investigational Site
  • Coppito, Italy, 67100
    • Recruiting
    • LEO Pharma Investigational Site
  • Modena, Italy, 41124
    • Recruiting
    • LEO Pharma Investigational Site
  • Napoli, Italy, 80131
    • Recruiting
    • LEO Pharma Investigational Site
  • Parma, Italy, 43126
    • Recruiting
    • LEO Pharma Investigational Site
  • Pavia, Italy, 27100
    • Completed
    • LEO Pharma Investigational Site
  • Roma, Italy, 00133
    • Recruiting
    • LEO Pharma Investigational Site
  • Roma, Italy, 00168
    • Recruiting
    • LEO Pharma Investigational Site
  • Rozzano, Italy, 20089
    • Recruiting
    • LEO Pharma Investigational Site
• Netherlands
  • Beek, Netherlands, 6191 JW
    • Recruiting
    • LEO Pharma Investigational Site
• Poland
  • Iwonicz-Zdrój, Poland, 38-440
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Lublin, Poland, 20-362
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Lublin, Poland, 20-412
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Poznań, Poland, 60-529
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Skierniewice, Poland, 96-100
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Warszawa, Poland, 02-482
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Warszawa, Poland, 02-758
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Warszawa, Poland, 02-801
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Wrocław, Poland, 50-566
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Wrocław, Poland, 51-318
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Wrocław, Poland, 52-416
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Łódź, Poland, 90-242
    • Active, not recruiting
    • LEO Pharma Investigational Site
  • Łódź, Poland, 90-436
    • Active, not recruiting
    • LEO Pharma Investigational Site
• Spain
  • Alicante, Spain, 03010
    • Recruiting
    • LEO Pharma Investigational Site
  • Badalona, Spain, 08916
    • Recruiting
    • LEO Pharma Investigational Site
  • Barcelona, Spain, 08025
    • Recruiting
    • LEO Pharma Investigational Site
  • Barcelona, Spain, 08035
    • Recruiting
    • LEO Pharma Investigational Site
  • Granada, Spain, 18014
    • Recruiting
    • LEO Pharma Investigational Site
  • Manises, Spain, 46940
    • Recruiting
    • LEO Pharma Investigational Site
  • Pontevedra, Spain, 36001
    • Recruiting
    • LEO Pharma Investigational Site
  • Pozuelo De Alarcón, Spain, 28223
    • Recruiting
    • LEO Pharma Investigational Site
  • Santiago De Compostela, Spain, 15706
    • Recruiting
    • LEO Pharma Investigational Site
  • Valencia, Spain, 46014
    • Recruiting
    • LEO Pharma Investigational Site
  • Villajoyosa, Spain, 03570
    • Recruiting
    • LEO Pharma Investigational Site
• United Kingdom
  • Chorley, United Kingdom, PR7 7NA
    • Recruiting
    • LEO Pharma Investigational Site
  • Corby, United Kingdom, NN18 9EZ
    • Recruiting
    • LEO Pharma Investigational Site
  • Corby, United Kingdom, NN17 2UR
    • Recruiting
    • LEO Pharma Investigational Site
  • Coventry, United Kingdom, CV3 4FJ
    • Recruiting
    • LEO Pharma Investigational Site
  • Liverpool, United Kingdom, L22 0LG
    • Recruiting
    • LEO Pharma Investigational Site
  • London, United Kingdom, BR5 3QG
    • Recruiting
    • LEO Pharma Investigational Site
  • London, United Kingdom, E1 2ES
    • Recruiting
    • LEO Pharma Investigational Site
  • Northwood, United Kingdom, HA6 2RN
    • Recruiting
    • LEO Pharma Investigational Site
  • Shipley, United Kingdom, BD18 35A
    • Recruiting
    • LEO Pharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brodalumab 210 mg + brodalumab 70 mg add-on* (adjusted brodalumab dosing regimen); Participants will receive 210 mg brodalumab subcutaneously at Week 0, Week 1, and Week 2, and then once every 2 weeks. *Participants not fulfilling a predefined response at any visit with efficacy assessments after Week 16 will receive a dose adjustment to 280 mg brodalumab every 2 weeks.	Biological: Brodalumab; Brodalumab is an anti-IL-17 receptor antibody, which blocks the inflammatory effects of IL-17 in the skin.
Placebo Comparator: Brodalumab 210 mg + placebo add-on* (standard brodalumab treatment); Participants will receive 210 mg brodalumab subcutaneously at Week 0, Week 1, and Week 2, and then once every 2 weeks. *Participants not fulfilling a predefined response at any time visit with efficacy assessments Week 16 will receive a dose adjustment to 210 mg brodalumab + placebo every 2 weeks.	Biological: Brodalumab; Brodalumab is an anti-IL-17 receptor antibody, which blocks the inflammatory effects of IL-17 in the skin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Having at least 90% lower Psoriasis Area and Severity Index (PASI) score relative to baseline (PASI 90 response) at Week 40.	The PASI score is the most widely used tool in clinical practice and clinical trials to assess the severity and extent of psoriasis. The assessment is done based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit. The investigator will assess the severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, according to a severity scale. The investigator will also assess the extent of psoriasis within each of the 4 body regions. This gives a composite score ranging from 0-72, with higher values indicating a more severe and/or more extensive condition.	Week 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Having static Physician's Global Assessment (sPGA) score of 0 or 1 at Week 40	The sPGA is an instrument used in clinical trials to rate the severity of the participant's global psoriasis and is based on a 6-point scale ranging from 0 (clear) to 5 (very severe).	Week 40
Having PASI 90 response at Week 52	The PASI score is the most widely used tool in clinical practice and clinical trials to assess the severity and extent of psoriasis. The assessment is done based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit. The investigator will assess the severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, according to a severity scale. The investigator will also assess the extent of psoriasis within each of the 4 body regions. This gives a composite score ranging from 0-72, with higher values indicating a more severe and/or more extensive condition. PASI 90 is defined as at least 90% improvement in PASI relative to baseline.	Week 52
Having sPGA score of 0 or 1 at Week 52	The sPGA is an instrument used in clinical trials to rate the severity of the participant's global psoriasis and is based on a 6-point scale ranging from 0 (clear) to 5 (very severe).	Week 52
Having sPGA of genitalia (sPGA-G) score of 0 or 1 at both Week 40 and Week 52	The sPGA-G score is based on a combination of erythema and the secondary features (plaque elevation and/or scale) and it is used to rate the severity of the participant's psoriasis of the genitalia on a 6-point scale ranging from 0 (clear) to 5 (very severe).	Week 40
Having sPGA of genitalia (sPGA-G) score of 0 or 1 at Week 40	The sPGA-G score is based on a combination of erythema and the secondary features (plaque elevation and/or scale) and it is used to rate the severity of the participant's psoriasis of the genitalia on a 6-point scale ranging from 0 (clear) to 5 (very severe).	Week 40
Having sPGA-G score of 0 or 1 at Week 52	The sPGA-G score is based on a combination of erythema and the secondary features (plaque elevation and/or scale) and it is used to rate the severity of the participant's psoriasis of the genitalia on a 6-point scale ranging from 0 (clear) to 5 (very severe).	Week 52
Having PASI 100 response at Week 40	The PASI score is the most widely used tool in clinical practice and clinical trials to assess the severity and extent of psoriasis. The assessment is done based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit. The investigator will assess the severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, according to a severity scale. The investigator will also assess the extent of psoriasis within each of the 4 body regions. This gives a composite score ranging from 0-72, with higher values indicating a more severe and/or more extensive condition. PASI 100 is defined as 100% improvement in PASI relative to baseline.	Week 40
Having PASI 100 response at Week 52	The PASI score is the most widely used tool in clinical practice and clinical trials to assess the severity and extent of psoriasis. The assessment is done based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit. The investigator will assess the severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, according to a severity scale. The investigator will also assess the extent of psoriasis within each of the 4 body regions. This gives a composite score ranging from 0-72, with higher values indicating a more severe and/or more extensive condition. PASI 100 is defined as 100% improvement in PASI relative to baseline.	Week 52
Change from baseline at Weeks 40 and 52 in PASI score	The PASI score is the most widely used tool in clinical practice and clinical trials to assess the severity and extent of psoriasis. The assessment is done based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit. The investigator will assess the severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, according to a severity scale. The investigator will also assess the extent of psoriasis within each of the 4 body regions. This gives a composite score ranging from 0-72, with higher values indicating a more severe and/or more extensive condition.	Week 40 and 52
Change from baseline at Weeks 40 and 52 in affected body surface area (BSA)	To assess the full BSA with psoriatic involvement, the investigator will use the surface area of the participant's hand (palm and fingers) as a reference measurement to determine the percentage of the body surface area that is affected by psoriasis. One hand is approximately equal to 1% total BSA.	Week 40 and 52
Having Dermatology Life Quality Index (DLQI) total score of 0 or 1 at Week 40	The Dermatology Life Quality Index (DLQI) is a validated questionnaire with content specific to those with dermatology conditions. The DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their HQoL 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 HQoL.	Week 40
Having DLQI total score of 0 or 1 at Week 52	The Dermatology Life Quality Index (DLQI) is a validated questionnaire with content specific to those with dermatology conditions. The DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their HQoL 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 HQoL.	Week 52
Change from baseline at Weeks 40 and 52 in DLQI total score	The Dermatology Life Quality Index (DLQI) is a validated questionnaire with content specific to those with dermatology conditions. The DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their health-related quality of life (HrQoL) over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment (10). 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 HrQoL.	Week 40 and 52
Number of Participants Experiencing Adverse Events (AEs) up to Week 58.		Week 58

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2022
• Primary Completion (Estimated): September 4, 2025
• Study Completion (Estimated): January 8, 2026

Study Registration Dates

• First Submitted: March 11, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Body Weight; Dermatologic Agents; Brodalumab
• Other Study ID Numbers: LP0160-1329; 2017-004998-13 (EudraCT Number); U1111-1282-4507 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• 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: Data-sharing is subject to approved scientifically sound research proposal and signed data-sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

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