E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Psoriatic arthritis is a type of inflammatory arthritis that can cause swelling, stiffness and pain in the joints.
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037160 |
E.1.2 | Term | Psoriatic arthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Demonstrate the clinical efficacy of bimekizumab administered subcutaneously (sc) compared with placebo in the treatment of subjects with active Psoriatic Arthritis (PsA), as assessed by the American College of Rheumatology 50% Improvement (ACR50) response
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E.2.2 | Secondary objectives of the trial |
-Assess the efficacy of bimekizumab compared with placebo
-Assess the safety and tolerability of bimekizumab
-Assess the impact of bimekizumab on patient-reported quality of life
-Assess the impact of bimekizumab on skin psoriasis (PSO) in the
subgroup of affected subjects at Baseline
-Assess the impact of bimekizumab on functional improvement
-Assess the impact of bimekizumab on radiographic changes in the
hands and feet
-Assess the impact of bimekizumab on extra-articular disease
manifestations (dactylitis, enthesitis)
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
For individuals consenting to the genomics, genetics, and proteomics substudy, blood samples will be drawn for exploratory genetic/epigenetic, genomic, proteomic, and metabolomics analysis and for candidate exploratory biomarker analyses.
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E.3 | Principal inclusion criteria |
- 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
American College of Rheumatology (ACR) 50 Response at Week 16
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16
2. 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
3. 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
4. Change from Baseline in the Short Form 36-item Health Survey (SF36) Physical Component Summary (PCS) at Week 16
5. Minimal Disease Activity (MDA) at Week 16
6. Change from Baseline in Van der Heijde modified Total Sharp Score
(vdHmTSS) in subjects with elevated high sensitivity C-reactive protein (hs-CRP) and/or at least 1 bone erosion at Baseline at Week 16
7. 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
8. 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
9. Change from Baseline in Van der Heijde modified Total Sharp Score
(vdHmTSS) in the overall population at Week 16
10. American College of Rheumatology (ACR) 20 response at Week 16
11. American College of Rheumatology (ACR) 70 Response at Week 16
12. 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
13. 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
14. Change from Baseline in the Patient's Assessment of Arthritis Pain
(PtAAP) at Week 16
15. 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
16. Change from Baseline in Psoriatic Arthritis Impact of Disease-12
(PsAID-12) total score at Week 16
17. Incidence of treatment-emergent adverse events (TEAEs) during the study
18. Incidence of treatment-emergent serious adverse events (SAEs)
during the study
19. Incidence of treatment-emergent adverse events (TEAEs) leading to withdrawal from investigational medicinal product (IMP) during the study
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 3-9, 13-16: Baseline, Week 16
2, 12: Baseline, Week 4
5, 10-11: Week 16
17-19: From Baseline until Safety Follow-Up
(up to Week 72)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, Tolerability |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 90 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Japan |
Russian Federation |
United States |
Belgium |
France |
Germany |
Hungary |
Italy |
Poland |
Spain |
United Kingdom |
Czechia |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last subject last visit (LSLV) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 23 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 13 |