A Study to Evaluate the Dose Response Based on the Efficacy, Safety and Tolerability of Bimekizumab in Subjects With Active Psoriatic Arthritis Which is a Type of Inflammatory Arthritis

Study Overview
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Brief Summary
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This is a study to evaluate the dose response based on the efficacy, safety and tolerability of bimekizumab in subjects with active psoriatic arthritis.

Official Title
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A Multicenter, Phase 2B, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Efficacy and Safety of Bimekizumab in Active Psoriatic Arthritis

Conditions
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Psoriatic Arthritis

Intervention / Treatment
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* Other: Placebo
* Drug: Bimekizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a documented diagnosis of adult-onset PsA classified by Classification Criteria for Psoriatic Arthritis (CASPAR) criteria with symptoms for at least 6 months prior to Screening, with active psoriatic arthritis (PsA) at Baseline/Day 1, and must have at Baseline tender joint count (TJC) >=3 out of 78 and swollen joint count (SJC) >=3 out of 76 Subject must be rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies negative Subject must have active psoriatic lesion(s) and/or a documented history of psoriasis Subjects who are regularly taking nonsteroidal anti-inflammatory drug (NSAIDs)/COX-2 inhibitors as part of their PsA therapy are required to be on a stable dose/dose regimen for at least 14 days before Baseline Subjects taking corticosteroids must be on an average daily dose of <=10mg/day prednisone or equivalent for at least 14 days before Baseline and should remain on a stable dose through the Week 16 visit Subjects taking methotrexate (MTX) (<=25mg /week) are allowed to continue their medication if started at least 12 weeks prior to Baseline, with a stable dose for at least 8 weeks before randomization Subjects taking leflunomide (LEF; <=20mg/day or an average of 20mg/day if not dosed daily) are allowed to continue their medication if started at least 3 months prior to Baseline, with a stable dose for at least 8 weeks before randomization. Dose and dosing schedule should remain stable up to Week 16 Subjects may be tumor necrosis factor (TNF) inhibitor naïve or may have received 1 prior TNF inhibitor. Subjects who have been on a TNF inhibitor previously must have: experienced an inadequate response to previous treatment given for at least 3 months been intolerant to administration (eg, had a side-effect/adverse event (AE) that led to discontinuation) lost access to TNF inhibitor for other reasons Exclusion Criteria: Subjects with any current sign or symptom that may indicate an active infection (with the exception of the common cold) or has had an infection requiring systemic antibiotics within 2 weeks of Baseline/Day 1 Subjects with a history of chronic or recurrent infections, or a serious or life-threatening infection within the 6 months prior to the Baseline Visit Subjects with concurrent acute or chronic viral hepatitis B or C or human immunodeficiency virus (HIV) infection Subjects with known history of or current clinically active infection with Histoplasma, Coccidioides, Paracoccidioides, Pneumocystis, Blastomyces, or Aspergillus or current active Candidiasis Subjects receiving any live (includes attenuated) vaccination within the 8 weeks prior to Baseline Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, with latent TB infection (LTBI), or current or history of nontuberculous mycobacteria (NTMB) infection Subjects with a diagnosis of inflammatory conditions other than psoriasis or psoriatic arthritis Subjects with concurrent malignancy or a history of malignancy during the past 5 years will be excluded, with following exceptions that may be included: <= 3 excised or ablated basal cell carcinomas of the skin One squamous cell carcinoma of the skin (stage T1 maximum) successfully excised, or ablated only (other treatments, ie, chemotherapy, do not apply), with no signs of recurrence or metastases for more than 2 years prior to Screening Actinic keratosis (-es) Squamous cell carcinoma-in-situ of the skin successfully excised, or ablated, more than 6 months prior to Screening

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects will receive for 12 Weeks Placebo and will then be re-randomized to Bimekizumab dosage regimen 2 or Bimekizumab dosage regimen 3 for 36 Weeks. | Other: Placebo<br> <br> |
| Experimental: Bimekizumab dosage regimen 1<br>Subjects will receive for 12 Weeks Bimekizumab dosage regimen 1 and will then be re-randomized to Bimekizumab dosage regimen 2 or Bimekizumab dosage regimen 3 for 36 Weeks. | Drug: Bimekizumab<br>* Bimekizumab in different dosage regimens.<br>* Other names: UCB4940;|
| Experimental: Bimekizumab dosage regimen 2<br>Subjects will receive for 48 Weeks Bimekizumab dosage regimen 2. | Drug: Bimekizumab<br>* Bimekizumab in different dosage regimens.<br>* Other names: UCB4940;|
| Experimental: Bimekizumab dosage regimen 3<br>Subjects will receive for 48 Weeks Bimekizumab dosage regimen 3. | Drug: Bimekizumab<br>* Bimekizumab in different dosage regimens.<br>* Other names: UCB4940;|
| Experimental: Bimekizumab dosage regimen 4<br>Subjects will receive for 12 Weeks Bimekizumab dosage regimen 4 and will then be re-randomized to Bimekizumab dosage regimen 2 for 36 Weeks. | Drug: Bimekizumab<br>* Bimekizumab in different dosage regimens.<br>* Other names: UCB4940;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR50 (American College of Rheumatology 50% Improvement) Response at Week 12 | The ACR50 response rate was based on 50% improvement relative to Baseline in the following measures: Tender Joint Count (TJC) based on 78 joints Swollen Joint Count (SJC) based on 76 joints 3 of the 5 remaining core set measures: Disease activity as assessed by Patient's Global Assessment of Disease Activity (PGADA) Disease activity as assessed by Physician's Global Assessment of Disease Activity (PhGADA) Pain as assessed by Patient's Assessment of Arthritis Pain (PtAAP) Physical function as assessed by Health Assessment Questionnaire - Disability Index (HAQ-DI) Acute phase response as assessed by high sensitivity C-reactive protein (hs CRP). | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20 (American College of Rheumatology 20% Improvement) Response at Week 12 | The ACR20 response rate was based on 20% improvement relative to Baseline in the following measures: TJC based on 78 joints SJC based on 76 joints 3 of the 5 remaining core set measures: Disease activity as assessed by PGADA Disease activity as assessed by PhGADA Pain as assessed by PtAAP Physical function as assessed by HAQ-DI Acute phase response as assessed by hs CRP Note: Nonresponder imputation was used to account for missing data in the primary analysis, the study participants with a missing ACR score at Week 12 or who discontinued IMP prior to the Week 12 Visit were considered nonresponders for the primary analysis. | Week 12 | 
| ACR70 (American College of Rheumatology 70% Improvement) Response at Week 12 | The ACR70 response rate was based on 70% improvement relative to Baseline in the following measures: TJC based on 78 joints SJC based on 76 joints 3 of the 5 remaining core set measures: Disease activity as assessed by PGADA Disease activity as assessed by PhGADA Pain as assessed by PtAAP Physical function as assessed by HAQ-DI Acute phase response as assessed by hs CRP Note: Nonresponder imputation was used to account for missing data in the primary analysis, the study participants with a missing ACR score at Week 12 or who discontinued IMP prior to the Week 12 Visit were considered nonresponders for the primary analysis. | Week 12 | 
| PASI90 (Psoriasis Area Severity Index) Response at Week 12 in the Subgroup of Subjects With Psoriasis Involving at Least 3 % Body Surface Area (BSA) at Baseline/Day 1 | 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 12 | 
| PASI75 (Psoriasis Area Severity Index) Response at Week 12 in the Subgroup of Subjects With Psoriasis Involving at Least 3 % Body Surface Area (BSA) at Baseline/Day 1 | 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 12 | 
| Percentage of Participants With at Least One Adverse Event (AE) During the Study | An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. | From Screening Period until the Safety Follow-Up Visit (up to Week 72) | 
| Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study | A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalization or prolongation of existing hospitalization Is a congenital anomaly or birth defect Is an infection that requires treatment parenteral antibiotics Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. | From Screening Period until the Safety Follow-Up Visit (up to Week 72) | 
| Percentage of Participants Who Withdrew Due to an Adverse Event (AE) During the Study | An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. | From Screening Period until the Safety Follow-Up Visit (up to Week 72) | 
| Changes From Baseline in Vital Signs During the Study (Diastolic Blood Pressure, Systolic Blood Pressure) | Diastolic and systolic blood pressure were measured in millimeters of mercury (mmHg). | Baseline, 30 min and 1 hour post dose, Week 1, Week 2, pre- and post dose for the following Weeks: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44 and Week 48 | 
| Changes From Baseline in Vital Signs During the Study (Pulse Rate) | Pulse rate was measured in beats per minute (beats/min). | Baseline, 30 min and 1 hour post dose, Week 1, Week 2, pre- and post dose for the following Weeks: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44 and Week 48 | 
| Changes From Baseline in Body Weight During the Study | Body weight was measured in kilograms. | Baseline, Week 12, Week 24, Week 36 and Week 48 | 
| Changes From Baseline in Electrocardiogram (ECG) Intervals During the Study (QTcB, QTcF, PR, QRS, QT, RR) | Electrocardiogram (ECG) intervals (QTcB= QT interval corrected for heart rate (Bazett's formula); QTcF= QT interval corrected for heart rate (Fridericia's formula)) were measured in milliseconds. | Baseline, Week 12 and Week 48 | 
| Changes From Baseline in Hematology Parameters During the Study (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils) | Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils were measured in number of white blood cells per liter (10^9/L). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Hematology Parameters During the Study (Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration, Hemoglobin) | Erythrocytes mean corpuscular hemoglobin (HGB) concentration and hemoglobin were measured in grams per liter (g/L). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Hematology Parameters During the Study (Erythrocytes Mean Corpuscular Hemoglobin (HGB)) | Erythrocytes mean corpuscular hemoglobin (HGB) was measured in picograms (pg). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Hematology Parameters During the Study (Erythrocytes Mean Corpuscular Volume) | Erythrocytes mean corpuscular volume was measured in femtolitres (fL). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Hematology Parameters During the Study (Erythrocytes) | Erythrocytes was measured in number of red blood cells per liter (10^12/L). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Hematology Parameters During the Study (Hematocrit) | Hematocrit was measured in volume percentage (%) of red blood cells in blood. | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Hematology Parameters During the Study (Platelets) | Platelets was measured in number of platelets per liter (10^9/L). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Biochemistry Parameters During the Study (Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, Lactate Dehydrogenase) | Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase were measured in units per liter (U/L). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Biochemistry Parameters During the Study (Albumin) | Albumin was measured in grams per liter (g/L). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Biochemistry Parameters During the Study (Bilirubin, Creatinine, Urate) | Bilirubin, creatinine, urate were measured in micromols per liter (μmol/L). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Biochemistry Parameters During the Study (Calcium, Chloride, Cholesterol, Glucose, Magnesium, Potassium, Sodium) | Calcium, chloride, cholesterol, glucose, magnesium, potassium, sodium were measured in millimoles per liter (mmol/L). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Biochemistry Parameters During the Study (Urea Nitrogen) | Urea nitrogen was measured in millimoles per liter (mmol/L). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Urinalysis Parameters During the Study (Erythrocytes, Leukocytes, Renal Epithelial Casts, Squamous Epithelial Cells, Transitional Epithelial Cells) | Erythrocytes, leukocytes, renal epithelial casts, squamous epithelial cells, transitional epithelial cells were measured in cells per high power field (cells/HPF). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Urinalysis Parameters During the Study (Hyaline Casts) | Hyaline casts was measured in cells per low power field (cells/LPF). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 
| Changes From Baseline in Urinalysis Parameters During the Study (pH) | Urine pH was measured on a pH scale. | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriatic Arthritis, PsA, Bimekizumab