A Study to Assess the Pharmacokinetics, Safety, and Efficacy of Two Doses of Bimekizumab in Adolescent Study Participants With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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The purpose of the study is to assess th pharmacokinetics (PK) of bimekizumab administered subcutaneously (sc) in adolescents with moderate to severe plaque psoriasis (PSO).

Official Title
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A Multicenter, Open-Label, Randomized Study to Assess the Pharmacokinetics, Safety, and Efficacy of Two Doses of Bimekizumab in Adolescent Study Participants With Moderate to Severe Plaque Psoriasis

Conditions
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Moderate to Severe Plaque Psoriasis

Intervention / Treatment
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* Drug: bimekizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be ≥12 to less than 18 years of age at the time of signing the informed consent/assent according to local regulation Participant has had a diagnosis of moderate to severe plaque psoriasis (PSO) for at least 3 months prior to the Screening Visit and: Body surface area (BSA) affected by PSO ≥10% Investigator's Global Assessment (IGA) score ≥3 (on a scale from 0 to 4) Psoriasis Area and Severity Index (PASI) score ≥12 OR PASI score ≥10 plus at least 1 of the following: i. Clinically relevant facial involvement ii. Clinically relevant genital involvement iii. Clinically relevant hand and foot involvement Participant must be candidate for systemic PSO therapy and/or photo/chemotherapy Body weight ≥30 kg and body mass index for age percentile of ≥5 at Baseline Male or female A female participant will be eligible to participate if she is not pregnant, not breastfeeding, and a woman of childbearing potential (WOCBP) agrees to follow the contraceptive guidance Capable of giving/having parent(s) or legal representative provide signed informed consent/assent (where appropriate) Exclusion Criteria: Participant has a presence of guttate, inverse, pustular, or erythrodermic PSO or other dermatological condition that may impact the clinical assessment of PSO Participant has a history of inflammatory bowel disease (IBD) or symptoms suggestive of IBD History of active tuberculosis unless successfully treated, latent TB unless prophylactically treated Participant has an active infection or history of infections (such as serious infection, chronic infections, opportunistic infections, unusually severe infections) Participant has laboratory abnormalities at Screening Participant has experienced primary failure to one or more interleukin-17 (IL-17) biologic response modifier OR primary failure to more than 1 biologic response modifier other than an IL-17 biologic response modifier Presence of active suicidal ideation, or positive suicide behavior Participant has been diagnosed with severe depression in the past 6 months

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bimekizumab Dose A<br>Study participants randomized to this arm will receive bimekizumab (BKZ) Dose A at pre-specified time points during the study. | Drug: bimekizumab<br>* Study participants will receive subcutaneously administered bimekizumab (BKZ) at pre-specified time points during the study.<br>* Other names: UCB4940;|
| Experimental: Bimekizumab Dose B<br>Study participants randomized to this arm will receive bimekizumab (BKZ) Dose B at pre-specified time points during the study. | Drug: bimekizumab<br>* Study participants will receive subcutaneously administered bimekizumab (BKZ) at pre-specified time points during the study.<br>* Other names: UCB4940;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of bimekizumab at Week 0 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 0. | Baseline (Week 0) | 
| Plasma concentration of bimekizumab at Week 1 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 1. | Week 1 | 
| Plasma concentration of bimekizumab at Week 4 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 4. | Week 4 | 
| Plasma concentration of bimekizumab at Week 8 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 8. | Week 8 | 
| Plasma concentration of bimekizumab at Week 12 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 12. | Week 12 | 
| Plasma concentration of bimekizumab at Week 16 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 16. | Week 16 | 
| Plasma concentration of bimekizumab at Week 20 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 20. | Week 20 | 
| Plasma concentration of bimekizumab at Week 36 | Blood samples will be collected at pre-specified time points at Week 36 to determine the bimekizumab plasma concentration, if participant is not eligible for the Open-label Extension (OLE) Period at Week 20 or does not wish to continue into the OLE Period. | Week 36 | 
| Plasma concentration of bimekizumab at Week 40 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 40. | Week 40 | 
| Plasma concentration of bimekizumab at Week 64 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 64. | Week 64 | 
| Plasma concentration of bimekizumab at Week 88 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 88. | Week 88 | 
| Plasma concentration of bimekizumab at Week 112 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 112. | Week 112 | 
| Plasma concentration of bimekizumab at Week 124 | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 124. | Week 124 | 
| Plasma concentration of bimekizumab at safety follow up (SFU) | Blood samples will be collected at pre-specified time points to determine the bimekizumab plasma concentration at Week 140 (SFU). | Week 140 (SFU) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with treatment-emergent adverse events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. Treatment-emergent AEs are defined as those AEs that have a start date on or following the first dose of IMP through the final dose of IMP + 20 weeks. | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140)] | 
| Percentage of participants with serious TEAEs | An serious adverse event (SAE) must meet 1 or more of the following criteria: Results in death Is life-threatening Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent disability/incapacity Is a congenital anomaly/birth defect Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or subject and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious. Treatment-emergent AEs are defined as those AEs that have a start date on or following the first dose of IMP through the final dose of IMP + 20 weeks. | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Percentage of participants with TEAEs leading to discontinuation of investigational medicinal product (IMP) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. Treatment-emergent AEs are defined as those AEs that have a start date on or following the first dose of IMP through the final dose of IMP + 20 weeks. This measure considers any TEAE leading to permanent discontinuation of IMP regardless of reason. | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Percentage of participants with selected safety topics of interest | Selected safety topics of interest (including infection [serious, opportunistic, fungal, and tuberculosis (TB)], inflammatory bowel disease [IBD], and injection site reactions) with onset occurring from day of first dose through 20 weeks after final dose of IMP adjusted by duration of participant exposure to IMP. | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in vital signs (systolic and diastolic blood pressure) | Blood pressure will be measured in millimeters of mercury (mmHg). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in vital signs (heart rate or pulse rate) | Heart rate will be measured in beats per minute (beats/min). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in vital signs (temperature) | Temperature (oral, axillary, otic or non-contact forehead) will be measured in degrees Celsius (°C). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in physical examination findings reported as TEAEs with onset occurring from day of first dose through 20 weeks after final dose of IMP | Clinically significant findings or worsening of previous findings since the physical examination at Baseline will be reported as TEAEs with onset occurring from day of first dose through 20 weeks after final dose of IMP. | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in hematology parameters (platelet count) | Platelets will be measured in number of platelets per liter (10^9/L). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in hematology parameters (mean corpuscular hemoglobin) | Mean corpuscular hemoglobin (HGB) will be measured in picograms (pg). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in hematology parameters (mean corpuscular volume) | Mean corpuscular volume will be measured in femtolitres (fL). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in hematology parameters (erythrocytes) | Erythrocytes will be measured in number of red blood cells per liter (10^12/L). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in hematology parameters (hemoglobin) | Hemoglobin will be measured in grams per liter (g/L). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in hematology parameters (hematocrit) | Hematocrit will be measured in volume percentage (%) of red blood cells in blood. | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in clinical chemistry parameters (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase) | Alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase will be measured in units per liter (U/L). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in hematology parameters (basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes) | Basophils, eosinophils, lymphocytes, monocytes, neutrophils and leukocytes will be measured in number of white blood cells per liter (10^9/L) | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in clinical chemistry parameters (calcium, potassium, sodium, blood urea nitrogen, glucose (nonfasting)) | Calcium, potassium, sodium, blood urea nitrogen, and glucose (non fasting) will be measured in millimoles per liter (mmol/L). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in clinical chemistry parameters (creatinine, total and direct bilirubin) | Creatinine and bilirubin will be measured in micromols per liter (μmol/L). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in clinical chemistry parameters (total protein) | Total protein will be measured in milligrams per liters (mg/L). | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in height | Growth assessment, as assessed by the change from Baseline in height. | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in weight | Growth assessment, as assessed by the change from Baseline in weight. | From day of first dose (Week 0) through 20 weeks after final dose of IMP (up to Week 140) | 
| Percentage of participants with Psoriasis Area and Severity Index (PASI) 90 response at Week 16 | The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. | Week 16 | 
| Percentage of participants with Investigator's Global Assessment (IGA) 0/1 (Clear [0]/Almost Clear [1] with at least 2-category improvement from Baseline) response at Week 16 | The Investigator's Global Assessment (IGA) measures the overall psoriasis severity following a 5-point scale (0-4), where scale 0= clear, no signs of psoriasis; presence of post-inflammatory hyperpigmentation, scale 1= almost clear, no thickening; normal to pink coloration; no to minimal focal scaling, scale 2= mild thickening, pink to light red coloration and predominately fine scaling, 3= moderate, clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling and 4= severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. IGA response (Clear or Almost Clear) is defined as clear [0] or almost clear [1] with at least a two-category improvement from Baseline. | Week 16 | 
| Percentage of participants with Psoriasis Area and Severity Index (PASI) 75 response at Week 4 | The PASI75 response assessments are based on at least 75% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. | Week 4 | 
| Percentage of participants with anti-bimekizumab antibody (AbAb) detection prior to investigational medicinal product (IMP) administration | Anti-bimekizumab antibody (AbAb) detection prior to investigational medicinal product (IMP) administration | Baseline (Week 0) | 
| Percentage of participants with anti-bimekizumab antibody (AbAb) detection following investigational medicinal product (IMP) administration | Anti-bimekizumab antibody (AbAb) detection following investigational medicinal product (IMP) administration | From Week 1 through 20 weeks after final dose of IMP (up to Week 140) | 
| Change from Baseline in Children's Dermatology Life Quality Index (CDLQI) response at Week 16 | The CDLQI is a questionnaire designed to measure the impact of skin diseases on the lives of children. The questionnaire consists of 10 questions that are based on the experiences of children with skin disease. The instrument asks participants about symptoms and feelings, leisure, school or holidays, personal relationships, sleep, and treatment. The questions relate to the impact of the skin disease on the child over the last week, (ie, over the last 7 days). The CDLQI total score ranges from 0 to 30 with higher scores indicating higher impact of skin disease on quality of life (Qol). | Week 16, compared to Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bimekizumab, BKZ, adolescent study participants, psoriasis, PSO