A Study to Test the Efficacy and Safety of Bimekizumab in the Treatment of Subjects With Active Psoriatic Arthritis (BE OPTIMAL)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03895203 |
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Recruitment Status :
Completed
First Posted : March 29, 2019
Last Update Posted : January 13, 2023
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Sponsor:
UCB Biopharma SRL
Information provided by (Responsible Party):
UCB Pharma ( UCB Biopharma SRL )
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Brief 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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Psoriatic Arthritis | Drug: Bimekizumab Drug: Adalimumab Other: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 852 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | April 3, 2019 |
| Actual Primary Completion Date : | August 17, 2021 |
| Actual Study Completion Date : | July 11, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Psoriatic arthritis
Drug Information available for:
Adalimumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Bimekzumab dosage regimen
Subjects randomized to this arm will receive assigned bimekizumab dosage regimen and placebo to maintain the blinding with adalimumab and placebo arms during the Treatment Period.
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Drug: Bimekizumab
Subjects will receive bimekizumab at pre-specified time-points.
Other Names:
Other: Placebo Subjects will receive placebo at pre-specified time-points.
Other Name: PBO |
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Active Comparator: Adalimumab dosage regimen
Subjects randomized to this arm will receive the assigned adalimumab dosage regimen during the Treatment Period.
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Drug: Adalimumab
Adalimumab will be administered according to the labeling recommendations.
Other Name: HUMIRA® |
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Placebo Comparator: Placebo
Subjects randomized to this arm will receive placebo during the Double-Blind Treatment Period and will be reallocated to receive bimekizumab dosage regimen during the Maintenance Period.
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Drug: Bimekizumab
Subjects will receive bimekizumab at pre-specified time-points.
Other Names:
Other: Placebo Subjects will receive placebo at pre-specified time-points.
Other Name: PBO |
Primary Outcome Measures :
- American College of Rheumatology (ACR) 50 response at Week 16 [ Time Frame: Week 16 ]The ACR50 response rate is based on a 50% or greater improvement of arthritis relative to Baseline.
Secondary Outcome Measures :
- Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16 [ Time Frame: Baseline, 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.
- 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 [ Time Frame: Baseline, Week 4 ]
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.
- 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 [ Time Frame: Baseline, Week 16 ]
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.
- Change from Baseline in the Short Form 36-item Health Survey (SF-36) Physical Component Summary (PCS) at Week 16 [ Time Frame: Baseline, 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.
- Minimal Disease Activity (MDA) at Week 16 [ Time Frame: 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
- 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 [ Time Frame: Baseline, 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.
- 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 [ Time Frame: Baseline, Week 16 ]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.
- 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 [ Time Frame: Baseline, Week 16 ]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.
- American College of Rheumatology (ACR) 20 response at Week 16 [ Time Frame: Week 16 ]The ACR20 response rate is based on a 20% or greater improvement of arthritis relative to Baseline.
- Change from Baseline in Van der Heijde modified Total Sharp Score (vdHmTSS) in the overall population at Week 16 [ Time Frame: Baseline, 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.
- American College of Rheumatology (ACR) 70 response at Week 16 [ Time Frame: Week 16 ]The ACR70 response rate is based on a 70% or greater improvement of arthritis relative to Baseline.
- 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 [ Time Frame: Baseline, Week 4 ]Investigator Global Assessment (IGA) response is defined as Clear or Almost Clear with at least a 2-category improvement relative to Baseline.
- 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 [ Time Frame: Baseline, Week 16 ]Investigator Global Assessment (IGA) response is defined as Clear or Almost Clear with at least a 2-category improvement relative to Baseline.
- Change from Baseline in the Patient's Assessment of Arthritis Pain (PtAAP) at Week 16: PtAAP Visual Analog Scale (VAS) [ Time Frame: Baseline, Week 16 ]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."
- 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 [ Time Frame: Baseline, Week 16 ]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.
- Change from Baseline in Psoriatic Arthritis Impact of Disease-12 (PsAID-12) total score at Week 16 [ Time Frame: Baseline, 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.
- Incidence of treatment-emergent adverse events (TEAEs) during the study [ Time Frame: From Baseline until Safety Follow-Up (up to Week 72) ]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.
- Incidence of treatment-emergent serious adverse events (SAEs) during the study [ Time Frame: From Baseline until Safety Follow-Up (up to Week 72) ]
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
- Incidence of treatment-emergent adverse events (TEAEs) leading to withdrawal from investigational medicinal product (IMP) during the study [ Time Frame: From Baseline until Safety Follow-Up (up to Week 72) ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03895203
Locations
Show 136 study locations
Sponsors and Collaborators
UCB Biopharma SRL
Investigators
| Study Director: | UCB Cares | 001 844 599 2273 |
| Responsible Party: | UCB Biopharma SRL |
| ClinicalTrials.gov Identifier: | NCT03895203 |
| Other Study ID Numbers: |
PA0010 2017-002322-20 ( EudraCT Number ) |
| First Posted: | March 29, 2019 Key Record Dates |
| Last Update Posted: | January 13, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion. |
| Access Criteria: | Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. |
| URL: | http://www.Vivli.org |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
Keywords provided by UCB Pharma ( UCB Biopharma SRL ):
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Psoriatic Arthritis PsA Bimekizumab |
Additional relevant MeSH terms:
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Arthritis Arthritis, Psoriatic Joint Diseases Musculoskeletal Diseases Spondylarthropathies Spondylarthritis Spondylitis Spinal Diseases |
Bone Diseases Psoriasis Skin Diseases, Papulosquamous Skin Diseases Adalimumab Anti-Inflammatory Agents Antirheumatic Agents |