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

Study Overview
=================
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.

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

Conditions
-----------------
Psoriasis

Intervention / Treatment
-----------------
* Drug: Brodalumab
* Drug: Ustekinumab
* Drug: Placebo


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

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. | 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. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 12 | 
| 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. | 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). | 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). | Week 12 | 
| Occurrence of adverse events up to Week 60. |  | Week 0 to Week 60 | 
| Presence of anti-drug antibodies, assessed 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. |  | Week 8, Week 12, and Week 52 | 
| Blood levels of T-cell subsets (CD4+ and CD8+), assessed 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. |  | 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. |  | Week 12 | 
| 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). | Week 12 | 
| 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). | Week 12 |