search
Back to results

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

Primary Purpose

Psoriasis

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Brodalumab
Ustekinumab
Placebo
Sponsored by
LEO Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Psoriasis

Eligibility Criteria

12 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharm Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site
  • LEO Pharma Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Placebo Comparator

Placebo Comparator

Arm Label

Brodalumab

Ustekinumab

Placebo/brodalumab

Placebo/ustekinumab

Arm Description

Brodalumab for 52 weeks. The dose will be determined by the participant's body weight.

Ustekinumab for 52 weeks. The dose will be determined by the participant's body weight.

Placebo for the first 12 weeks and brodalumab for the following 40 weeks. The dose will be determined by the participant's body weight.

Placebo for the first 12 weeks and ustekinumab for the following 40 weeks. The dose will be determined by the participant's body weight.

Outcomes

Primary Outcome Measures

Psoriasis Area and Severity Index (PASI) 75 response, assessed at Week 12.
Having at least 75% improvement in PASI score from baseline. The PASI 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 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.

Secondary Outcome Measures

Static Physician's Global Assessment (sPGA) score of 0 or 1, assessed at Week 12.
Achieving a score of 0 (clear) or 1 (almost clear) in sPGA. 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).
sPGA score of 0, assessed at Week 12.
Achieving a score of 0 (clear) in sPGA. 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).
PASI 90 response, assessed at Week 12.
Having at least 90% improvement in PASI score from baseline. The PASI 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 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.
PASI 100 response, assessed at Week 12.
Having at least 100% improvement in PASI score from baseline. The PASI 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 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.
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).
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).
Occurrence of adverse events up to Week 60.
Presence of anti-drug antibodies, assessed at Weeks 4, 16, and 52.
Serum concentration of interleukin-17, assessed at Weeks 8, 12, and 52.
Blood levels of T-cell subsets (CD4+ and CD8+), assessed at Weeks 8, 12, and 52.
Serum concentrations of brodalumab, assessed at Weeks 4, 8, 10, 12, 16, 22, and 52.
Anti-tetanus toxoid antibodies ≥0.1 IU/mL, assessed at Week 12.

Full Information

First Posted
March 10, 2020
Last Updated
September 13, 2023
Sponsor
LEO Pharma
search

1. Study Identification

Unique Protocol Identification Number
NCT04305327
Brief Title
Efficacy and Safety of Brodalumab in Adolescents From 12 to 17 Years of Age With Moderate-to-severe Plaque Psoriasis
Acronym
EMBRACE 1
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Early terminated due to difficulty recruiting participants
Study Start Date
October 18, 2022 (Actual)
Primary Completion Date
June 27, 2023 (Actual)
Study Completion Date
June 27, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LEO Pharma

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Double-blind until Week 12, where the primary endpoint is assessed. Open-label active comparator treatment from Week 0 to Week 52, but with blinded outcomes assessor throughout the study.
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Brodalumab
Arm Type
Experimental
Arm Description
Brodalumab for 52 weeks. The dose will be determined by the participant's body weight.
Arm Title
Ustekinumab
Arm Type
Active Comparator
Arm Description
Ustekinumab for 52 weeks. The dose will be determined by the participant's body weight.
Arm Title
Placebo/brodalumab
Arm Type
Placebo Comparator
Arm Description
Placebo for the first 12 weeks and brodalumab for the following 40 weeks. The dose will be determined by the participant's body weight.
Arm Title
Placebo/ustekinumab
Arm Type
Placebo Comparator
Arm Description
Placebo for the first 12 weeks and ustekinumab for the following 40 weeks. The dose will be determined by the participant's body weight.
Intervention Type
Drug
Intervention Name(s)
Brodalumab
Other Intervention Name(s)
Kyntheum®
Intervention Description
Solution for subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
Ustekinumab
Other Intervention Name(s)
Stelara®
Intervention Description
Solution for subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
The placebo solution is similar to the active brodalumab solution except that it does not contain any active substance.
Primary Outcome Measure Information:
Title
Psoriasis Area and Severity Index (PASI) 75 response, assessed at Week 12.
Description
Having at least 75% improvement in PASI score from baseline. The PASI 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 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.
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Static Physician's Global Assessment (sPGA) score of 0 or 1, assessed at Week 12.
Description
Achieving a score of 0 (clear) or 1 (almost clear) in sPGA. 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).
Time Frame
Week 12
Title
sPGA score of 0, assessed at Week 12.
Description
Achieving a score of 0 (clear) in sPGA. 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).
Time Frame
Week 12
Title
PASI 90 response, assessed at Week 12.
Description
Having at least 90% improvement in PASI score from baseline. The PASI 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 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.
Time Frame
Week 12
Title
PASI 100 response, assessed at Week 12.
Description
Having at least 100% improvement in PASI score from baseline. The PASI 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 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.
Time Frame
Week 12
Title
Children's Dermatology Life Quality Index (CDLQI) total score of 0 or 1, assessed at Week 12.
Description
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).
Time Frame
Week 12
Title
Family Dermatology Life Quality Index (FDLQI) total score of 0 or 1, assessed at Week 12.
Description
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).
Time Frame
Week 12
Title
Occurrence of adverse events up to Week 60.
Time Frame
Week 0 to Week 60
Title
Presence of anti-drug antibodies, assessed at Weeks 4, 16, and 52.
Time Frame
Week 4, Week 16, and Week 52
Title
Serum concentration of interleukin-17, assessed at Weeks 8, 12, and 52.
Time Frame
Week 8, Week 12, and Week 52
Title
Blood levels of T-cell subsets (CD4+ and CD8+), assessed at Weeks 8, 12, and 52.
Time Frame
Week 8, Week 12, and Week 52
Title
Serum concentrations of brodalumab, assessed at Weeks 4, 8, 10, 12, 16, 22, and 52.
Time Frame
Week 4, Week 8, Week 10, Week 12, Week 16, Week 22, and Week 52
Title
Anti-tetanus toxoid antibodies ≥0.1 IU/mL, assessed at Week 12.
Time Frame
Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Expert
Organizational Affiliation
LEO Pharma
Official's Role
Study Director
Facility Information:
Facility Name
LEO Pharma Investigational Site
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
LEO Pharma Investigational Site
City
Liège
ZIP/Postal Code
B-4000
Country
Belgium
Facility Name
LEO Pharma Investigational Site
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
LEO Pharma Investigational Site
City
Bad Bentheim
ZIP/Postal Code
48455
Country
Germany
Facility Name
LEO Pharma Investigational Site
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
LEO Pharma Investigational Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
LEO Pharma Investigational Site
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
LEO Pharma Investigational Site
City
Hamburg
ZIP/Postal Code
20537
Country
Germany
Facility Name
LEO Pharma Investigational Site
City
Langenau
ZIP/Postal Code
89129
Country
Germany
Facility Name
LEO Pharma Investigational Site
City
Lübeck
ZIP/Postal Code
23538
Country
Germany
Facility Name
LEO Pharm Investigational Site
City
Mainz
ZIP/Postal Code
55128
Country
Germany
Facility Name
LEO Pharma Investigational Site
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
LEO Pharma Investigational Site
City
Athens
ZIP/Postal Code
124-62
Country
Greece
Facility Name
LEO Pharma Investigational Site
City
Piraeus
ZIP/Postal Code
18536
Country
Greece
Facility Name
LEO Pharma Investigational Site
City
Thessaloníki
ZIP/Postal Code
54643
Country
Greece
Facility Name
LEO Pharma Investigational Site
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
LEO Pharma Investigational Site
City
Orosháza
ZIP/Postal Code
5900
Country
Hungary
Facility Name
LEO Pharma Investigational Site
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
LEO Pharma Investigational Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
LEO Pharma Investigational Site
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
LEO Pharma Investigational Site
City
Iwonicz-Zdrój
ZIP/Postal Code
38-440
Country
Poland
Facility Name
LEO Pharma Investigational Site
City
Poznań
ZIP/Postal Code
60-529
Country
Poland
Facility Name
LEO Pharma Investigational Site
City
Skierniewice
ZIP/Postal Code
96-100
Country
Poland
Facility Name
LEO Pharma Investigational Site
City
Warszawa
ZIP/Postal Code
01-817
Country
Poland
Facility Name
LEO Pharma Investigational Site
City
Warszawa
ZIP/Postal Code
02-482
Country
Poland
Facility Name
LEO Pharma Investigational Site
City
Wrocław
ZIP/Postal Code
50-566
Country
Poland
Facility Name
LEO Pharma Investigational Site
City
Wrocław
ZIP/Postal Code
51-318
Country
Poland
Facility Name
LEO Pharma Investigational Site
City
Wrocław
ZIP/Postal Code
52-416
Country
Poland
Facility Name
LEO Pharma Investigational Site
City
Łódź
ZIP/Postal Code
90-436
Country
Poland
Facility Name
LEO Pharma Investigational Site
City
Alicante
ZIP/Postal Code
03010
Country
Spain
Facility Name
LEO Pharma Investigational Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
LEO Pharma Investigational Site
City
Granada
ZIP/Postal Code
18014
Country
Spain
Facility Name
LEO Pharma Investigational Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
LEO Pharma Investigational Site
City
Pontevedra
ZIP/Postal Code
36001
Country
Spain
Facility Name
LEO Pharma Investigational Site
City
Valencia
ZIP/Postal Code
46018
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
Data-sharing is subject to approved scientifically sound research proposal and signed data-sharing agreement.
IPD Sharing URL
http://leopharmatrials.com/for-professionals

Learn more about this trial

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

We'll reach out to this number within 24 hrs