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

Psoriatic Arthritis Clinical Trial

— BE ACTIVE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02969525
• Other study ID #: PA0008
• Secondary ID: 2016-001103-23
• Status: Completed
• Phase: Phase 2
• Start date: October 2016
• Est. completion date: July 2018

Study information

• Verified date: March 2023
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: July 2018
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. experienced an inadequate response to previous treatment given for at least 3 months

2. been intolerant to administration (eg, had a side-effect/adverse event (AE) that led to discontinuation)

3. 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:

1. <= 3 excised or ablated basal cell carcinomas of the skin

2. 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

3. Actinic keratosis (-es)

4. Squamous cell carcinoma-in-situ of the skin successfully excised, or ablated, more than 6 months prior to Screening

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Other:
• Placebo

Drug:
• Bimekizumab
Bimekizumab in different dosage regimens.

Locations

Country	Name	City	State
Czechia	Pa0008 205	Brno
Czechia	Pa0008 207	Olomouc
Czechia	Pa0008 210	Praha 11
Czechia	Pa0008 202	Praha 2
Czechia	Pa0008 201	Praha 4
Czechia	Pa0008 209	Praha 4
Czechia	Pa0008 203	Zlin
Germany	Pa0008 302	Cologne
Germany	Pa0008 309	Erlangen
Germany	Pa0008 304	Hamburg
Germany	Pa0008 301	Ratingen
Hungary	Pa0008 403	Budakeszierdo
Hungary	Pa0008 401	Veszprem
Poland	Pa0008 452	Bialystok
Poland	Pa0008 453	Elblag
Poland	Pa0008 456	Elblag
Poland	Pa0008 455	Krakow
Poland	Pa0008 451	Poznan
Poland	Pa0008 450	Torun
Poland	Pa0008 454	Warszawa
Poland	Pa0008 459	Warszawa
Poland	Pa0008 465	Wroclaw
Russian Federation	Pa0008 604	Moscow
Russian Federation	Pa0008 605	Moscow
Russian Federation	Pa0008 607	Moscow
Russian Federation	Pa0008 606	Saint Petersburg
Russian Federation	Pa0008 608	Saint Petersburg
United States	Pa0008 005	Aventura	Florida
United States	Pa0008 004	Charleston	South Carolina
United States	Pa0008 006	Dallas	Texas
United States	Pa0008 001	Duncansville	Pennsylvania
United States	Pa0008 003	Hagerstown	Maryland
United States	Pa0008 010	Jackson	Tennessee
United States	Pa0008 012	Johnston	Rhode Island
United States	Pa0008 011	Lansing	Minnesota
United States	Pa0008 025	Lexington	New York
United States	Pa0008 013	Mesquite	Texas
United States	Pa0008 014	Portland	Oregon
United States	Pa0008 007	San Diego	California
United States	Pa0008 002	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma S.P.R.L.

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Hungary,  Poland,  Russian Federation, 

References & Publications (1)

Mease PJ, Asahina A, Gladman DD, Tanaka Y, Tillett W, Ink B, Assudani D, de la Loge C, Coarse J, Eells J, Gossec L. Effect of bimekizumab on symptoms and impact of disease in patients with psoriatic arthritis over 3 years: results from BE ACTIVE. Rheumato — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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