Efficacy and Safety of Brodalumab in Adolescents From 12 to 17 Years of Age With Moderate-to-severe Plaque Psoriasis (EMBRACE 1)

A Phase 3, Randomised, Double-blind, Multi-centre Trial to Evaluate the Efficacy, Safety, and Tolerability of Brodalumab Treatment Compared to Placebo and Ustekinumab in Adolescent Subjects With Moderate-to-severe Plaque Psoriasis

The study will investigate the efficacy and safety compared to placebo and the safety compared to ustekinumab of brodalumab in adolescents with moderate to severe plaque psoriasis. The study will also investigate if brodalumab affects development of vaccination-induced immune responses.

The study will run over 62-64 weeks (including screening, treatment, and safety follow-up) for each participant, but with the primary endpoint measured at Week 12.

Study Overview

• Status: Terminated
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Brodalumab; Drug: Ustekinumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • LEO Pharma Investigational Site
  • Liège, Belgium, B-4000
    • LEO Pharma Investigational Site
• France
  • Toulouse, France, 31059
    • LEO Pharma Investigational Site
• Germany
  • Bad Bentheim, Germany, 48455
    • LEO Pharma Investigational Site
  • Essen, Germany, 45122
    • LEO Pharma Investigational Site
  • Frankfurt, Germany, 60590
    • LEO Pharma Investigational Site
  • Hamburg, Germany, 20537
    • LEO Pharma Investigational Site
  • Hamburg, Germany, 20246
    • LEO Pharma Investigational Site
  • Langenau, Germany, 89129
    • LEO Pharma Investigational Site
  • Lübeck, Germany, 23538
    • LEO Pharma Investigational Site
  • Mainz, Germany, 55128
    • LEO Pharm Investigational Site
  • Münster, Germany, 48149
    • LEO Pharma Investigational Site
• Greece
  • Athens, Greece, 124-62
    • LEO Pharma Investigational Site
  • Piraeus, Greece, 18536
    • LEO Pharma Investigational Site
  • Thessaloníki, Greece, 54643
    • LEO Pharma Investigational Site
• Hungary
  • Debrecen, Hungary, 4032
    • LEO Pharma Investigational Site
  • Orosháza, Hungary, 5900
    • LEO Pharma Investigational Site
• Italy
  • Brescia, Italy, 25123
    • LEO Pharma Investigational Site
  • Napoli, Italy, 80131
    • LEO Pharma Investigational Site
  • Padova, Italy, 35128
    • LEO Pharma Investigational Site
• Poland
  • Iwonicz-Zdrój, Poland, 38-440
    • LEO Pharma Investigational Site
  • Poznań, Poland, 60-529
    • LEO Pharma Investigational Site
  • Skierniewice, Poland, 96-100
    • LEO Pharma Investigational Site
  • Warszawa, Poland, 01-817
    • LEO Pharma Investigational Site
  • Warszawa, Poland, 02-482
    • LEO Pharma Investigational Site
  • Wrocław, Poland, 51-318
    • LEO Pharma Investigational Site
  • Wrocław, Poland, 52-416
    • LEO Pharma Investigational Site
  • Wrocław, Poland, 50-566
    • LEO Pharma Investigational Site
  • Łódź, Poland, 90-436
    • LEO Pharma Investigational Site
• Spain
  • Alicante, Spain, 03010
    • LEO Pharma Investigational Site
  • Barcelona, Spain, 08041
    • LEO Pharma Investigational Site
  • Granada, Spain, 18014
    • LEO Pharma Investigational Site
  • Madrid, Spain, 28046
    • LEO Pharma Investigational Site
  • Pontevedra, Spain, 36001
    • LEO Pharma Investigational Site
  • Valencia, Spain, 46018
    • LEO Pharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Subject was diagnosed with chronic plaque psoriasis at least 6 months before randomisation.
• Subject has a diagnosis of moderate-to-severe plaque psoriasis as defined by PASI ≥12, sPGA ≥3, and body surface area ≥10% at screening and at baseline.
• Subject, in whom topical therapy is not adequate, and who is a candidate for systemic therapy.
• Subject has no evidence of active or latent tuberculosis according to local standard of care.

Key Exclusion Criteria:

• Subject is diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, or other skin conditions (e.g., eczema).
• Subject has been vaccinated with a tetanus toxoid-containing vaccine ≤18 months prior to first dose of investigational medicinal product (IMP). For EU and UK: Subject has been vaccinated with a TT-containing vaccine within 5 years prior to the first dose of IMP.
• Subject has developed or experienced either Guillian-Barre syndrome, encephalopathy, Arthus-type hypersensitivity, or severe allergic reactions in connection with previous Tdap or Td vaccine.
• Subject with chronic or recurrent infections, or active infection, systemically treated within 4 weeks prior to first dose of IMP.
• Subject has a known history of Crohn's disease.
• Subject has any active malignancy or a history of any malignancy within 5 years.
• Subject has a history of suicidal behaviour and has suicidal ideation with some intent to act or specific plan and intent.
• Subject has a history of depressive disorder with severe episode(s) within the last 2 years.
• Subject has received anti-IL-12/23p40 for less than 12 months prior to the first dose of IMP or has previously no response to anti-IL-12/23p40 therapy.
• Subject has previously received anti-IL-17 therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brodalumab; Brodalumab for 52 weeks. The dose will be determined by the participant's body weight.	Drug: Brodalumab; Solution for subcutaneous injection.; Other Names: Kyntheum®
Active Comparator: Ustekinumab; Ustekinumab for 52 weeks. The dose will be determined by the participant's body weight.	Drug: Ustekinumab; Solution for subcutaneous injection.; Other Names: Stelara®
Placebo Comparator: Placebo/brodalumab; Placebo for the first 12 weeks and brodalumab for the following 40 weeks. The dose will be determined by the participant's body weight.	Drug: Brodalumab; Solution for subcutaneous injection.; Other Names: Kyntheum®; Drug: Placebo; The placebo solution is similar to the active brodalumab solution except that it does not contain any active substance.
Placebo Comparator: Placebo/ustekinumab; Placebo for the first 12 weeks and ustekinumab for the following 40 weeks. The dose will be determined by the participant's body weight.	Drug: Ustekinumab; Solution for subcutaneous injection.; Other Names: Stelara®; Drug: Placebo; The placebo solution is similar to the active brodalumab solution except that it does not contain any active substance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psoriasis Area and Severity Index (PASI) 75 Response, Assessed at Week 12.	PASI 75 response is defined as having at least 75% improvement in PASI score from baseline. 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, were assessed according to a severity scale. The extent of psoriasis within each of the 4 body regions was also assessed. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe and/or more extensive condition.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Static Physician's Global Assessment (sPGA) Score of 0 or 1, Assessed at Week 12.	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). The number of participants achieving a score of 0 (clear) or 1 (almost clear) was assessed.	Week 12
sPGA Score of 0, Assessed at Week 12.	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). The number of participants achieving a score of 0 (clear) or 1 (almost clear) was assessed.	Week 12
PASI 90 Response, Assessed at Week 12.	PASI 90 response is defined as having at least 90% improvement in PASI score from baseline. 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, will be assessed according to a severity scale. The extent of psoriasis within each of the 4 body regions will also be assessed. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe and/or more extensive condition.	Baseline to Week 12
PASI 100 Response, Assessed at Week 12.	PASI 100 response is defined as having at least 100% improvement in PASI score from baseline. 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, will be assessed according to a severity scale. The extent of psoriasis within each of the 4 body regions will also be assessed. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe and/or more extensive condition.	Baseline to Week 12
Children's Dermatology Life Quality Index (CDLQI) Total Score of 0 or 1, Assessed at Week 12.	CDLQI consists of 10 items addressing the child's perception of the impact of their skin disease on various aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, leisure, school or holidays, personal relationships, sleep, and the treatment. Each item is scored on a 4-point scale ranging from 0 (not at all) to 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.	Week 12
Family Dermatology Life Quality Index (FDLQI) Total Score of 0 or 1, Assessed at Week 12.	FDLQI consists of 10 items addressing the participant's relative perception of the impact of the participant's skin disease on various aspects of his/her quality of life over the last month such as: emotional distress, social life, job and leisure activities, physical well-being, time spent on helping the subject with e.g., treatment procedures, extra housework, and routine household expenditure. Each item is scored on a 4-point scale ranging from 0 (not at all) to 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.	Week 12
Overall Number of Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in subjects or clinical investigation participants administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the patient or may require medical or surgical intervention to prevent any of the outcomes listed above.	Up to approximately 5 months
Presence of Anti-drug Antibodies, Assessed at Weeks 4, 16, and 52.	Number of participants with a positive post-baseline anti-drug antibody result at weeks 4, 16, and 52.	Week 4, Week 16, and Week 52
Serum Concentration of Interleukin-17, Assessed at Weeks 8, 12, and 52.	Number of participants with detectable levels of Interleukin-17 at weeks 8, 12, and 52.	Week 8, Week 12, and Week 52
Blood Levels of T-cell Subsets (CD4+ and CD8+), Assessed at Weeks 8, 12, and 52.	Number of participants with detectable levels of T-cell subsets at weeks 8, 12, and 52.	Week 8, Week 12, and Week 52
Serum Concentrations of Brodalumab, Assessed at Weeks 4, 8, 10, 12, 16, 22, and 52.	Number of participants with detectable levels of brodalumab at weeks 4, 8, 10, 12, 16, 22, and 52.	Week 4, Week 8, Week 10, Week 12, Week 16, Week 22, and Week 52
Anti-tetanus Toxoid Antibodies ≥0.1 IU/mL, Assessed at Week 12.	Number of participants with detectable levels of anti-tetanus toxoid antibodies at weeks 12.	Week 12

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2022
• Primary Completion (Actual): May 5, 2023
• Study Completion (Actual): May 5, 2023

Study Registration Dates

• First Submitted: March 10, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

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

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases, Papulosquamous; Skin Diseases; Psoriasis; Dermatologic Agents; Ustekinumab; Brodalumab
• Other Study ID Numbers: LP0160-1396; 2019-001868-30 (EudraCT Number); U1111-1282-4459 (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 after 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