A Study to Test the Efficacy and Safety of Bimekizumab in the Treatment of Subjects With Active Psoriatic Arthritis

Psoriatic Arthritis Clinical Trial

— BE OPTIMAL  

Official title:

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Active Reference (Adalimumab) Study Evaluating the Efficacy and Safety of Bimekizumab in the Treatment of Subjects With Active Psoriatic Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03895203
• Other study ID #: PA0010
• Secondary ID: 2017-002322-20
• Status: Completed
• Phase: Phase 3
• Start date: April 3, 2019
• Est. completion date: July 11, 2022

Study information

• Verified date: April 2024
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study to demonstrate the clinical efficacy, safety and tolerability of bimekizumab administered subcutaneously (sc) compared with placebo in the treatment of subjects with active Psoriatic Arthritis (PsA).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 852
• Est. completion date: July 11, 2022
• Est. primary completion date: August 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the subject
• Subject is male or female at least 18 years of age
• Female subject must be postmenopausal, permanently sterilized or willing to use a highly effective method of contraception
• Documented diagnosis of adult-onset Psoriatic Arthritis (PsA) meeting the Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 6 months prior to Screening with active PsA and must have at Baseline tender joint count (TJC) >=3 out of 68 and swollen joint count (SJC) >=3 out of 66
• Subject must be negative for rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies
• Subject must have at least 1 active psoriatic lesion(s) and/or a documented history of psoriasis (PSO)
• Subject must be a suitable candidate for treatment with adalimumab and has no contraindications to receive adalimumab as per the local label as assessed by the Investigator
• Subjects currently taking NSAIDs, cyclooxygenase 2 (COX-2) inhibitors, analgesics (including mild opioids), corticosteroids, methotrexate (MTX), leflunomide (LEF), sulfasalazine (SSZ), hydroxychloroquine (HCQ) AND/OR apremilast can be allowed if they fulfill specific requirements prior to study entry

Exclusion Criteria:

• Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study
• Subjects with current or prior exposure to any biologics for the treatment of Psoriatic Arthritis (PsA) or Psoriasis (PSO)
• Subject has an active infection or a history of recent serious infections
• Subject has known tuberculosis (TB) infection, is at high risk of acquiring TB infection, or has current or history of nontuberculous mycobacterium (NTMB) infection
• Subject has a diagnosis of inflammatory conditions other than PSO or PsA. Subjects with a diagnosis of Crohn's disease, ulcerative colitis, or other inflammatory bowel disease (IBD) are allowed as long as they have no active symptomatic disease at Screening or Baseline
• Subject had acute anterior uveitis within 6 weeks of Baseline
• Subject has any active malignancy or history of malignancy within 5 years prior to the Screening Visit EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, or in situ cervical cancer
• Subject has a form of PSO other than chronic plaque-type (eg, pustular, erythrodermic and guttate PSO, or drug-induced PSO)
• Presence of active suicidal ideation, or moderately severe major depression or severe major depression
• Subject has a history of chronic alcohol or drug abuse within 6 months prior to Screening

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Drug:
• Bimekizumab
Subjects will receive bimekizumab at pre-specified time-points.
• Adalimumab
Adalimumab will be administered according to the labeling recommendations.

Other:
• Placebo
Subjects will receive placebo at pre-specified time-points.

Locations

Country	Name	City	State
Australia	Pa0010 30005	Camberwell
Australia	Pa0010 30002	Clayton
Australia	Pa0010 30008	Hobart
Australia	Pa0010 30003	Maroochydore
Australia	Pa0010 30007	Victoria Park
Australia	Pa0010 30006	Woodville
Belgium	Pa0010 40003	Genk
Belgium	Pa0010 40002	Leuven
Belgium	Pa0010 40059	Mons
Canada	Pa0010 50041	Québec City
Canada	Pa0010 50042	Rimouski
Canada	Pa0010 50043	Sidney
Canada	Pa0010 50044	Trois-Rivières
Czechia	Pa0010 40061	Brno
Czechia	Pa0010 40065	Brno
Czechia	Pa0010 40062	Ostrava
Czechia	Pa0010 40009	Pardubice
Czechia	Pa0010 40015	Praha
Czechia	Pa0010 40013	Praha 11
Czechia	Pa0010 40066	Praha 2
Czechia	Pa0010 40014	Praha 4
Czechia	Pa0010 40063	Praha 5
Czechia	Pa0010 40010	Uherské Hradište
Czechia	Pa0010 40012	Zlín
France	Pa0010 40019	Paris
France	Pa0010 40068	Tours
Germany	Pa0010 40074	Bad Doberan
Germany	Pa0010 40025	Berlin
Germany	Pa0010 40028	Berlin
Germany	Pa0010 40076	Cottbus
Germany	Pa0010 40023	Erlangen
Germany	Pa0010 40117	Frankfurt
Germany	Pa0010 40029	Hamburg
Germany	Pa0010 40071	Hamburg
Germany	Pa0010 40027	Herne
Germany	Pa0010 40078	Leipzig
Germany	Pa0010 40348	Magdeburg
Germany	Pa0010 40026	Ratingen
Hungary	Pa0010 40081	Budapest
Hungary	Pa0010 40083	Budapest
Hungary	Pa0010 40032	Debrecen
Hungary	Pa0010 40030	Eger
Hungary	Pa0010 40082	Kistarcsa
Hungary	Pa0010 40033	Székesfehérvár
Hungary	Pa0010 40079	Szentes
Hungary	Pa0010 40080	Szombathely
Italy	Pa0010 40084	Catania
Italy	Pa0010 40087	Milano
Italy	Pa0010 40085	Pisa
Italy	Pa0010 40086	Reggio Emilia
Japan	Pa0010 20035	Bunkyo-Ku
Japan	Pa0010 20043	Itabashi
Japan	Pa0010 20036	Kawachi-Nagano-shi
Japan	Pa0010 20045	Kita
Japan	Pa0010 20049	Kitakyushu
Japan	Pa0010 20044	Minato-Ku
Japan	Pa0010 20033	Nagoya
Japan	Pa0010 20041	Osaka
Japan	Pa0010 20046	Osaka
Japan	Pa0010 20048	Saitama
Japan	Pa0010 20031	Sapporo-City
Japan	Pa0010 20042	Sasebo
Japan	Pa0010 20032	Suita
Japan	Pa0010 20030	Tokyo
Poland	Pa0010 40093	Bialystok
Poland	Pa0010 40119	Bydgoszcz
Poland	Pa0010 40038	Elblag
Poland	Pa0010 40088	Elblag
Poland	Pa0010 40096	Gdynia
Poland	Pa0010 40042	Kraków
Poland	Pa0010 40092	Kraków
Poland	Pa0010 40037	Lublin
Poland	Pa0010 40091	Nowa Sól
Poland	Pa0010 40044	Poznan
Poland	Pa0010 40090	Poznan
Poland	Pa0010 40118	Torun
Poland	Pa0010 40041	Warszawa
Poland	Pa0010 40094	Warszawa
Poland	Pa0010 40097	Warszawa
Poland	Pa0010 40098	Warszawa
Poland	Pa0010 40039	Wroclaw
Poland	Pa0010 40043	Wroclaw
Poland	Pa0010 40095	Wroclaw
Russian Federation	Pa0010 20002	Moscow
Russian Federation	Pa0010 20005	Moscow
Russian Federation	Pa0010 20010	Moscow
Russian Federation	Pa0010 20017	Moscow
Russian Federation	Pa0010 20013	Petrozavodsk
Russian Federation	Pa0010 20012	Ryazan'
Russian Federation	Pa0010 20016	Ryazan'
Russian Federation	Pa0010 20001	Saint Petersburg
Russian Federation	Pa0010 20003	Saint Petersburg
Russian Federation	Pa0010 20004	Saint Petersburg
Russian Federation	Pa0010 20009	Saint Petersburg
Russian Federation	Pa0010 20083	Saint Petersburg
Russian Federation	Pa0010 20007	Saratov
Russian Federation	Pa0010 20014	Ulyanovsk
Russian Federation	Pa0010 20006	Vladimir
Russian Federation	Pa0010 20008	Yaroslavl
Russian Federation	Pa0010 20015	Yaroslavl
Spain	Pa0010 40105	Córdoba
Spain	Pa0010 40045	Coruña
Spain	Pa0010 40102	Málaga
Spain	Pa0010 40101	Sabadell
Spain	Pa0010 40104	Santiago De Compostela
Spain	Pa0010 40049	Sevilla
Spain	Pa0010 40103	Sevilla
Spain	Pa0010 40106	Sevilla
Spain	Pa0010 40099	Vigo
United Kingdom	Pa0010 40111	Leeds
United Kingdom	Pa0010 40107	Wolverhampton
United States	Pa0010 50029	Albuquerque	New Mexico
United States	Pa0010 50039	Atlanta	Georgia
United States	Pa0010 50002	Austin	Texas
United States	Pa0010 50050	Beckley	West Virginia
United States	Pa0010 50010	Brooklyn	New York
United States	Pa0010 50125	Charlotte	North Carolina
United States	Pa0010 50049	Corpus Christi	Texas
United States	Pa0010 50040	Dayton	Ohio
United States	Pa0010 50020	Duncansville	Pennsylvania
United States	Pa0010 50015	Hagerstown	Maryland
United States	Pa0010 50051	Houston	Texas
United States	Pa0010 50001	Jackson	Tennessee
United States	Pa0010 50008	Johnston	Rhode Island
United States	Pa0010 50028	Lexington	Kentucky
United States	Pa0010 50012	Memphis	Tennessee
United States	Pa0010 50036	Mesquite	Texas
United States	Pa0010 50007	Orangeburg	South Carolina
United States	Pa0010 50033	Palm Harbor	Florida
United States	Pa0010 50017	Phoenix	Arizona
United States	Pa0010 50016	Saint Louis	Missouri
United States	Pa0010 50035	San Diego	California
United States	Pa0010 50037	Tampa	Florida
United States	Pa0010 50004	Tustin	California
United States	Pa0010 50009	Waco	Texas
United States	Pa0010 50006	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  Japan,  Poland,  Russian Federation,  Spain,  United Kingdom, 

References & Publications (2)

Mease PJ, Warren RB, Nash P, Grouin JM, Lyris N, Willems D, Taieb V, Eells J, McInnes IB. Comparative Effectiveness of Bimekizumab and Secukinumab in Patients with Psoriatic Arthritis at 52 Weeks Using a Matching-Adjusted Indirect Comparison. Rheumatol Th — View Citation

Ritchlin CT, Coates LC, McInnes IB, Mease PJ, Merola JF, Tanaka Y, Asahina A, Gossec L, Gottlieb AB, Warren RB, Ink B, Bajracharya R, Shende V, Coarse J, Landewe RB. Bimekizumab treatment in biologic DMARD-naive patients with active psoriatic arthritis: 5 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	American College of Rheumatology (ACR) 50 response at Week 16	The ACR50 response rate is based on a 50% or greater improvement of arthritis relative to Baseline.	Week 16
Secondary	Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16	HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Thus, the mean also has a range from 0-3. Change from baseline is computed as the value at Week 16 minus the baseline value. A negative value in change from baseline indicates an improvement.	Baseline, Week 16
Secondary	Psoriasis Area Severity Index 90 (PASI90) response at Week 4 in the subgroup of subjects with psoriasis (PSO) involving at least 3% body surface area (BSA) at Baseline	The Psoriasis Area Severity Index 90 (PASI90) response is based on at least 90% improvement in the PASI score compared to Baseline.; The PASI 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.	Baseline, Week 4
Secondary	Psoriasis Area Severity Index 90 (PASI90) response at Week 16 in the subgroup of subjects with psoriasis (PSO) involving at least 3% body surface area (BSA) at Baseline	The Psoriasis Area Severity Index 90 (PASI90) response is based on at least 90% improvement in the PASI score compared to Baseline.; The PASI 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.	Baseline, Week 16
Secondary	Change from Baseline in the Short Form 36-item Health Survey (SF-36) Physical Component Summary (PCS) at Week 16	There are 8 SF-36 domain scores. In addition to domain scores, the PCS scores are calculated from the 8 domains. Each of the 8 domain scores and the component summary scores ranging from 0 to 100, with higher scores indicating better health status. A larger positive value in change from Baseline indicates an improvement.	Baseline, Week 16
Secondary	Minimal Disease Activity (MDA) at Week 16	Minimal Disease Activity (MDA) is a state of disease activity deemed a useful target of treatment by both the patient and physician, given current treatment possibilities and limitations. Criteria covering all domains of the disease have been developed to determine whether or not a patient has reached MDA based on key outcome measures in Psoriatic Arthritis (PsA).; A subject is considered as having MDA if 5 or more of the following 7 criteria are fulfilled: 1) Tender joint count <=1, 2) Swollen joint count <=1, 3) PASI <=1 or BSA <=3; 4) Patient pain Visual Analog Scale (VAS) <=15, 5) Patient global activity VAS <=20, 6) Health Assessment Questionnaire - Disability Index (HAQ-DI) <=0.5 and 7) Tender enthesial points <=1	Week 16
Secondary	Change from Baseline in Van der Heijde modified Total Sharp Score (vdHmTSS) in subjects with elevated hs-CRP and/or at least 1 bone erosion at Baseline at Week 16	The degree of joint damage is to be assessed using the vdHmTSS as used in the evaluation of Psoriatic Arthritis (PsA) compared to Baseline. This methodology quantifies the extent of joint erosions and joint space narrowing for 64 and 52 joints, respectively, with higher scores representing greater damage.	Baseline, Week 16
Secondary	Enthesitis-free state in the Leeds Enthesitis Index (LEI) at Week 16 in the subgroup of subjects with enthesitis at Baseline in the pooled population of PA0010 and PA0011	Presence of enthesitis will be assessed in the subgroup of subjects with enthesitis by palpation on the lateral epicondyles of the humerus (elbows), medial femoral epicondyles (knees), and Achilles tendons (heels) bilaterally and scored as 0=no pain and 1=painful at Baseline.	Baseline, Week 16
Secondary	Dactylitis-free state based on the Leeds Dactylitis Index (LDI) at Week 16 in the subgroup of subjects with dactylitis at Baseline in the pooled population of PA0010 and PA0011	Presence of dactylitis will be assessed in the subgroup of subjects with dactylitis using the LDI basic which evaluates for a >=10% difference in the circumference of the digit compared to the opposite digit this is then multiplied by the tenderness score, using a simple grading system (0=absent, 1=present) at Baseline.	Baseline, Week 16
Secondary	American College of Rheumatology (ACR) 20 response at Week 16	The ACR20 response rate is based on a 20% or greater improvement of arthritis relative to Baseline.	Week 16
Secondary	Change from Baseline in Van der Heijde modified Total Sharp Score (vdHmTSS) in the overall population at Week 16	The degree of joint damage is to be assessed using the vdHmTSS as used in the evaluation of Psoriatic Arthritis (PsA) compared to Baseline. This methodology quantifies the extent of joint erosions and joint space narrowing for 64 and 52 joints, respectively, with higher scores representing greater damage.	Baseline, Week 16
Secondary	American College of Rheumatology (ACR) 70 response at Week 16	The ACR70 response rate is based on a 70% or greater improvement of arthritis relative to Baseline.	Week 16
Secondary	Investigator Global Assessment (IGA) response defined as score of 0 (clear) or 1 (almost clear) AND at least a 2-grade reduction from Baseline at Week 4 in the subset of subjects with psoriatic skin lesions at Baseline	Investigator Global Assessment (IGA) response is defined as Clear or Almost Clear with at least a 2-category improvement relative to Baseline.	Baseline, Week 4
Secondary	Investigator Global Assessment (IGA) response defined as score of 0 (clear) or 1 (almost clear) AND at least a 2-grade reduction from Baseline at Week 16 in the subset of subjects with psoriatic skin lesions at Baseline	Investigator Global Assessment (IGA) response is defined as Clear or Almost Clear with at least a 2-category improvement relative to Baseline.	Baseline, Week 16
Secondary	Change from Baseline in the Patient's Assessment of Arthritis Pain (PtAAP) at Week 16: PtAAP Visual Analog Scale (VAS)	The PtAAP Visual Analog Scale (VAS) or 'Pain VAS' is part of the American College of Rheumatology (ACR) core set of measures in arthritis. Subjects will assess their arthritis pain using a VAS where 0 is "no pain" and 100 is "most severe pain."	Baseline, Week 16
Secondary	Enthesitis-free state based on the Spondyloarthritis Research Consortium of Canada (SPARCC) index at Week 16 in the subgroup of subjects with enthesitis at Baseline	Presence of enthesitis will be assessed in the subgroup of subjects with enthesitis at Baseline. The SPARCC is an index that measures the severity of enthesitis through the assessment of 16 sites. Tenderness on examination is recorded as either present (1) or absent (0) for each of the 16 sites, for an overall score range of 0 to 16.	Baseline, Week 16
Secondary	Change from Baseline in Psoriatic Arthritis Impact of Disease-12 (PsAID-12) total score at Week 16	The PsAID-12 total score is a patient-reported outcome measure for assessing the impact of Psoriatic Arthritis (PsA) in 12 physical and psychological domains, including pain, fatigue, skin problems, work and/or leisure activities, functional capacity, discomfort, sleep disturbance, coping, anxiety/fear/uncertainty, embarrassment and/or shame, social participation, and depression. Each domain is assessed with a single question using a 0 to 10 numerical rating scale. Each domain score is multiplied by a weighting factor and the results are then summed to provide the total score. The total score ranges from 0 to 10, with higher scores indicating a worse status. A score below 4 out of 10 is considered a patient-acceptable status. A change of 3 or more points is considered relevant absolute change.	Baseline, Week 16
Secondary	Incidence of treatment-emergent adverse events (TEAEs) during the study	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. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	From Baseline until Safety Follow-Up (up to Week 72)
Secondary	Incidence of treatment-emergent serious adverse events (SAEs) 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 Baseline until Safety Follow-Up (up to Week 72)
Secondary	Incidence of treatment-emergent adverse events (TEAEs) leading to withdrawal from investigational medicinal product (IMP) during the study	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. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	From Baseline until Safety Follow-Up (up to Week 72)