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

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

400

The mean age of all study participants was 50.52 years of age with a range of 20.0 to 85.0 years of age. Slightly over half of the participants were female (52.5%), and the majority of study participants were White (96.0%), and not of Hispanic or Latino ethnicity (99.0%). The mean body weight and mean BMI overall were 85.99kg and 29.76kg/m2, respectively. For both treatment groups, the proportions of study participants enrolled in each region were similar. The mean time since diagnosis of PsA was 9.50 years overall (range: 0.4 to 56 years). The majority of study participants had the polyarticular symmetric arthritis subtype of PsA (63.5%). Treatment groups were generally well balanced with respect to PsA-related and other Baseline disease characteristics. The mean time since diagnosis of PSO was 17.41 years overall (range: 0.0 to 58.5 years). The mean Psoriasis Area Severity Index (PASI) score was 9.58 and 66.0% of study participants had >=3% of BSA affected by PSO. Overall, 60.5% of study participants had nail PSO, 12.0% of study participants had dactylitis,and approximately 40% had enthesitis (43.3% by SPARCC and 35.5% by Leeds Enthesitis Index (LEI)). The majority of study participants had an inadequate response to 1 TNFa inhibitor (76.5%), with the remaining study participants having had an inadequate response to 2 TNFa inhibitors (11.3%) or intolerance to TNFa inhibitors (12.3%). Overall, 63.0% of the study participants had prior exposure to one or more cDMARDs. At Baseline, the majority of study participants were using NSAID therapy (55.8%) and/or cDMARDs (50.5%, primarily MTX [42.5%]). Overall, the mean TJC and SJC total scores were 18.69 (range: 3.0 to 67.0) and 9.87 (range: 3.0 to 56.0), respectively, with higher scores indicating more severe disease; median TJC and SJC total scores across groups were 15.00 and 7.00, respectively. The geometric mean hs-CRP level was 4.803mg/L.

A total of 400 study participants were randomized and started the Double-Blind Treatment Period as follows: 267 study participants in the bimekizumab 160mg Q4W group and 133 study participants in the placebo group. A total of 388 study participants (97.0%) completed the Double-Blind Treatment Period and a total of 378 study participants (94.5%) entered the OLE study. Out of the 22 study participants who did not enter the OLE study, a total of 6 study participants completed the SFU Period Overall, the percentages of study participants who completed the study were high and similar between treatment groups (98.5% and 94.0% in the bimekizumab 160mg Q4W and placebo groups, respectively). The most frequently reported primary reasons for discontinuation during the study were withdrawal by study participant (5 study participants [1.3%]) and lack of efficacy (3 study participants [0.8%]); the incidence of withdrawal was numerically lower in the Bimekizumab 160mg Q4W group (0.4%) compared with the placebo group (3.0%). Two study participants (0.7%) in the bimekizumab 160mg Q4W discontinued due to AE; no participants in the placebo group discontinued for this reason.

During the study, TEAEs were reported at a higher incidence in the bimekizumab 160mg Q4W group (108 study participants [40.4%] reported 206 TEAEs) compared with the placebo group (44 study participants [33.3%] reported 64 TEAEs). The incidences of serious TEAEs, TEAEs leading to study discontinuation, TEAEs leading to discontinuation of IMP, and severe TEAEs were low in the bimekizumab 160mg Q4W group: 5 study participants (1.9%) reported 5 serious TEAEs, 2 study participants (0.7%) reported 2 TEAEs leading to study discontinuation, 2 study participants (0.7%) reported 2 TEAEs leading to discontinuation of IMP, and 5 study participants (1.9%) reported 6 severe TEAEs. No study participants in the placebo group reported serious TEAEs, TEAEs leading to study discontinuation, TEAEs leading to discontinuation of IMP, or severe TEAEs. Drug-related TEAEs (as determined by the Investigator) were reported at a higher incidence in the bimekizumab 160mg Q4W group (35 study participants [13.1%] reported 53 TEAEs) compared with the placebo group (4 study participants [3.0%] reported 6 TEAEs). No deaths were reported during the study in either treatment group. Treatment-emergent AEs were most frequently reported in the SOC of Infections and infestations and at a higher incidence for the bimekizumab 160mg Q4W group (58 study participants [21.7%]) compared with the placebo group (18 study participants [13.6%]). Of the most commonly reported TEAEs, by PT, the incidences were numerically higher in the bimekizumab 160mg Q4W group compared with the placebo group for oral candidiasis (7 study participants [2.6%] vs 0 study participants, respectively), nasopharyngitis (10 study participants [3.7%] vs 1 study participant [0.8%], respectively), and upper respiratory tract infection (6 study participants [2.2%] vs 2 study participants [1.5%], respectively). The TEAE of corona virus infection was reported at a numerically lower incidence in the bimekizumab 160mg Q4W group compared with the placebo group (5 study participants [1.9%] vs 6 study participants [4.5%], respectively), and was the most commonly reported TEAE, by PT, in the placebo group.

Bimekizumab 160mg Q4W treatment demonstrated a superior ACR50 responder rate at Week 16 (primary efficacy variable) compared with placebo (43.4% vs 6.8%, respectively) . This difference was considered clinically meaningful, with a statistically significant odds ratio versus placebo of 11.086 (p<0.001).

The bimekizumab 160mg Q4W group had a greater mean decrease from Baseline (ie, improvement) in HAQ-DI compared with the placebo group at Week 16 (-0.3751 vs -0.0701, respectively; p<0.001); this difference was statistically significant and considered clinically meaningful (difference almost reaching the clinically meaningful within-patient threshold of 0.35) In study participants with PSO involving at least 3% BSA at Baseline, the bimekizumab 160mg Q4W group had a higher PASI90 responder rate compared with the placebo group at Week 16 (68.8% vs 6.8%, respectively; p<0.001); this difference was statistically significant and considered clinically meaningful.

Bimekizumab treatment led to superior improvements in joint and skin efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis and inadequate response or intolerance to TNFa inhibitors. The safety profile of bimekizumab was consistent with previous phase 3 studies in patients with plaque psoriasis, and studies of IL-17A inhibitors.

June. 07, 2024

Dec. 06, 2022

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02303-0/fulltext

Yes

Data from this study 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 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.clinicalstudydatarequest.com 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 a determination is made that the data cannot be adequately anonymized.

UCB Japan Co., Ltd

8-17-1 Nishi-shinjuku, Shinjuku-ku, Tokyo

CTR_SCC_UCBJapan@UCB.com

UCB Japan Co., Ltd

8-17-1 Nishi-shinjuku, Shinjuku-ku, Tokyo

+81-368647587

CTR_SCC_UCBJapan@UCB.com

completed

Aug. 15, 2019

Interventional

Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

treatment purpose

3

-Subject is male or female at least 18 years of age
-Female subjects 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 has a history of inadequate response (lack of efficacy after at least 3 months of therapy at an approved dose) or intolerance to treatment with 1 or 2 tumor necrosis factor alpha (TNF(alpha)) inhibitors for either PsA or PSO
-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

-Female subjects who are breastfeeding(including pumping), pregnant, or plan to become pregnant during the study
-Subjects with current or prior exposure to any biologics except tumor necrosis factor (TNF) inhibitors for the treatment of PsA or 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 including, but not limited to RA, sarcoidosis, systemic lupus erythematosus, reactive arthritis, Crohn's disease, or ulcerative colitis.

Both

psoriatic arthritis

investigational material(s)
Generic name etc : UCB4940
INN of investigational material : bimekizumab
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material : 160mg administered by sc injection

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

efficacy
American College of Rheumatology (ACR) 50 response at Week 16

safety
efficacy
-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
-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
-Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16
-Change from Baseline in the Short Form 36-item Health Survey (SF-36) Physical Component Summary (PCS) at Week 16
-Minimal Disease Activity (MDA) at Week 16
-American College of Rheumatology (ACR) 20 response at Week 16
-American College of Rheumatology (ACR) 70 response at Week 16
-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 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
-Change from Baseline in the Patient's Assessment of Arthritis Pain (PtAAP) at Week 16
-Change from Baseline in Psoriatic Arthritis Impact of Disease-12 (PsAID-12) at Week 16
-Incidence of treatment-emergent adverse events (TEAEs) during the study
-Incidence of serious adverse events (SAEs) during the study
-Adverse events (AEs) leading to withdrawal from investigational medicinal product (IMP) during the study

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July. 09, 2019