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A multicenter, open-label study to assess the long-term safety, torelability, and efficacy of bimekizumab in adult subjects with moderate to severe chronic plaque psoriasis

A multicenter, open-label study to assess the long-term safety, torelability, and efficacy of bimekizumab in adult subjects with moderate to severe chronic plaque psoriasis

1353

Cohort A: The mean age of all study participants was 45.4 years of age with a range of 18 to 83 years of age. The majority of all study participants were male (71.8%). The mean body weight and BMI were 89.67kg and 29.83kg/m2, respectively. In OLE2 Period Groups, the mean age of all study participants in CA-OL2S at the start of the feeder studies was 47.0 years of age with a range of 18 to 83 years of age. The majority of study participants were male (70.8%). The mean body weight and BMI were 93.71kg and 31.64kg/m2, respectively. Cohort B: In the PSO group, the mean age of all study participants was 48.8 years of age with a range of 21 to 78 years of age. The majority of study participants were male (80.0%) and all were Asian (100%). The mean body weight and BMI were 75.95kg and 27.07kg/m2, respectively. In the GPP group, the mean age of all study participants was 46.0 years of age with a range of 21 to 61 years of age. The majority of study participants were male (60.0%) and all were Asian (100%). The mean body weight and BMI were 68.04kg and 24.25kg/m2, respectively. In the EP group, the mean age of all study participants was 55.3 years of age with a range of 27 to 74 years of age. All study participants were male (100%) and Asian (100%). The mean body weight and BMI were 76.66kg and 27.80kg/m2, respectively.

Cohort A: A total of 1289 study participants signed the ICF in Cohort A, and a total of 1287 study participants were randomized in Cohort A and started the study with bimekizumab treatment as follows: 70 study participants in the bimekizumab 320mg Q4W group, 833 study participants in the bimekizumab 320mg Q4W/Q8W group, and 384 study participants in the bimekizumab 320mg Q8W group. Overall, 1072 study participants (83.3%) completed the Treatment Period (defined as completing the Week 144 Visit); the percentages of study participants who completed the Treatment Period were high in the bimekizumab 320mg Q4W/Q8W group (89.6%) and the bimekizumab 320mg Q8W group (84.9%). No study participant in the bimekizumab 320mg Q4W group completed the Treatment Period due to a mandatory dosing interval switch based on Protocol Amendment 3 or discontinuation. The most frequently reported primary reasons for discontinuation during the Treatment Period for the bimekizumab 320mg Q4W group were AE (24 study participants [34.3%]), consent withdrawn by study participant (17 study participants [24.3%]), and lost to follow up (14 study participants [20.0%]). In OLE2 Period Groups, a total of 318 study participants started the OLE2 Period and received treatment as follows: 226 study participants in Group A bimekizumab 320mg Q8W, 41 study participants in Group B bimekizumab 320mg Q4W/Q8W, and 51 study participants in Group B bimekizumab 320mg Q8W. Overall, 304 study participants in the bimekizumab total group (95.6%) completed the OLE2 Period; the percentages of study participants who completed the OLE2 Period were 95.6% of study participants in Group A bimekizumab 320mg Q8W, 95.1% of study participants in Group B bimekizumab 320mg Q4W/Q8W, and 96.1% of study participants in Group B bimekizumab 320mg Q8W.The most frequently reported primary reason for discontinuation during the OLE2 Period in the CA-OL2S bimekizumab total group was due to an AE (5 study participants [1.6%]), followed by lost to follow up (4 study participants [1.3%]). Cohort B: In Cohort B, a total of 75 study participants signed the ICF and were screened for the study, 9 of whom were screen failures due to ineligibility. A total of 66 study participants were enrolled in Cohort B and received bimekizumab treatment as follows: 45 study participants with plaque PSO, 10 study participants with GPP, and 11 study participants with EP. Overall, 60 and 57 study participants completed Week 48 and Week 96, respectively. The percentage of study participants who completed the Treatment Period was high (56 study participants [84.8%]). A total of 10 study participants discontinued during the Treatment Period as follows: 7 study participants (15.6%) in the PSO group, 2 study participants (20%) in the GPP group, and 1 study participant (9.1%) in the EP group. The most common reason for discontinuation was AEs (6 study participants [9.1%]) followed by lack of efficacy (2 study participants [3.0%]).

Cohort A: Treatment-emergent AEs through Week 144 were reported by 1150 study participants (89.4%) overall; when adjusted for duration of exposure, the resulting EAIR was 141.63/100 participant years overall and was higher in the bimekizumab 320mg Q4W group (179.68/100 participant years) compared with the bimekizumab 320mg Q8W group (97.83/100 participant-years). Overall, TEAEs through Week 144 were most frequently reported in the System Organ Classes (SOCs) of Infections and infestations (907 study participants [70.5%]), Skin and subcutaneous tissue disorders (354 study participants [27.5%]), Musculoskeletal and connective tissue disorders (305 study participants [23.7%]), Gastrointestinal disorders (285 study participants [22.1%]), and Injury, poisoning and procedural complications (211 study participants [16.4%]). Treatment emergent AEs were reported at a higher EAIR for the bimekizumab 320mg Q4W group compared with the 320mg Q8W group for Infections and infestations (93.50/100 participant years vs 45.51/100 participant years, respectively), Skin and subcutaneous tissue disorders (17.98/100 participant years vs 12.12/100 participant years, respectively), Musculoskeletal and connective tissue disorders (12.73/100 participant years vs 9.71/100 participant years, respectively), Gastrointestinal disorders (15.16/100 participant years vs 7.60/100 participant years, respectively), and Injury, poisoning and procedural complications (9.41/100 participant years vs 5.84/100 participant years, respectively). The most frequently reported TEAEs overall, by preferred term (PT), through Week 144 were nasopharyngitis (296 study participants [23.0%]), oral candidiasis (227 study participants [17.6%]), corona virus infection (201 study participants [15.6%]), and upper respiratory tract infection (162 study participants [12.6%]). When comparing the bimekizumab 320mg Q4W group with the bimekizumab 320mg Q8W group, the EAIR was higher in the bimekizumab 320mg Q4W group compared with the bimekizumab 320mg Q8W group for nasopharyngitis (20.19/100 participant years vs 6.85/100 participant years, respectively), oral candidiasis (16.33/100 participant years vs 5.58/100 participant years, respectively), and upper respiratory tract infection (7.84/100 participant years vs 4.18/100 participant years, respectively); the EAIR was lower in the bimekizumab 320mg Q4W group compared with the bimekizumab 320mg Q8W group for corona virus infection (1.80/100 participant years vs 7.85/100 participant years, respectively). During the OLE2 Period in the CA-OL2S, in the bimekizumab total group, 183 study participants (57.5%; EAIR=80.91/100 participant years) experienced TEAEs. During the OLE2 Period in the CA-OL2S, in the bimekizumab total group, TEAEs were most frequently reported in the SOC of Infections and infestations (128 study participants [40.3%]). The most frequently reported TEAEs, by PT, were corona virus infection (45 study participants [14.2%]), oral candidiasis (22 study participants [6.9%]), and nasopharyngitis (16 study participants [5.0%]). Cohort B: Treatment-emergent AEs were reported by 45 study participants (100%) in the PSO group, and when the TEAE incidence was adjusted for duration of exposure, the resulting EAIR was 244.08/100 participant-years. Treatment-emergent AEs were most frequently reported in the SOCs of Infections and infestations (39 study participants [86.7%]), Skin and subcutaneous tissue disorders (31 study participants [68.9%]), Gastrointestinal disorders (22 study participants [48.9%]), and General disorders and administration site conditions and Musculoskeletal and connective tissue disorders (15 study participants [33.3%] each). The most frequently reported TEAEs, by PT, were nasopharyngitis (19 study participants [42.2%]), eczema (15 study participants [33.3%]), oral candidiasis (11 study participants [24.4%]), and pyrexia (10 study participants [22.2%]). Treatment-emergent AEs were reported by 9 of 10 study participants in the GPP group, and when the TEAE incidence was adjusted for duration of exposure, the resulting EAIR was 188.71/100 participant-years. Treatment-emergent AEs were most frequently reported in the SOCs of Skin and subcutaneous tissue disorders (7 of 10 study participants), Gastrointestinal disorders and Infections and infestations (6 of 10 study participants each), and General disorders and administration site conditions and Investigations (3 of 10 study participants each). The most frequently reported TEAEs, by PT, were pyrexia (3 of 10 study participants; however, these were assessed as related to COVID-19 vaccines in 2 out of 3 study participants), diarrhea, chronic gastritis, oral candidiasis, nasopharyngitis, ALT increased, acne, and pustular psoriasis (2 of 10 study participants each). Treatment-emergent AEs were reported by 11 of 11 study participants in the EP group, and when the TEAE incidence was adjusted for duration of exposure, the resulting EAIR was 328.25/100 participant-years. Treatment-emergent AEs were most frequently reported in the SOCs of Infections and infestations (9 of 11 study participants) and Skin and subcutaneous tissue disorders (8 of 11 study participants). The most frequently reported TEAEs, by PT, were nasopharyngitis (7 of 11 study participants), oral candidiasis (4 of 11 study participants), eczema (3 of 11 study participants), vertigo, cellulitis, and EP (2 of 11 study participants each).

Refer to Adverse events.

Cohort A: At PS0014 Baseline, the proportion of study participants who achieved PASI90 was lower in the bimekizumab 320mg Q4W/Q8W group (87.1%) compared with the bimekizumab 320mg Q8W group (99.2%). In the bimekizumab 320mg Q4W/Q8W group, PASI90 response rates increased to Week 12 (NRI method: 94.5%, OC method: 96.1%) and were generally sustained at high levels through Week 144 (NRI method: 80.2%, OC method: 91.1%). In the bimekizumab 320mg Q8W group, the high level of PS0014 Baseline PASI90 response rate was generally sustained through Week 144 (NRI method: 77.6%, OC method: 94.6%). At PS0014 Baseline, the proportion of study participants who achieved IGA 0/1 response was lower in the bimekizumab 320mg Q4W/Q8W group (88.0%) compared with the bimekizumab 320mg Q8W group (96.9%). In the bimekizumab 320mg Q4W/Q8W group, IGA 0/1 response rates increased slightly to Week 12 (NRI method: 91.9%, OC method: 93.8%) and was generally sustained at high levels through Week 144 (NRI method: 79.0%, OC method: 90.0%). In the bimekizumab 320mg Q8W group, the high level of PS0014 Baseline IGA 0/1 response rates was generally sustained through Week 144 (NRI method: 76.8%, OC method: 93.7%). During the OLE2 Period, for study participants in Group A (continuous treatment) bimekizumab 320mg Q8W, the PASI90 response rate was generally sustained through OLE2 Period Week 48, and the IGA 0/1 response rate was generally sustained through OLE2 Period Week 36 and was slightly decreased at OLE2 Period Week 48. Study participants in Group B (interrupted treatment) bimekizumab 320mg Q4W/Q8W (IGA >=3 at Week 144/OLE2 Period Baseline) rapidly regained PASI90 response by OLE2 Period Week 12, and the PASI90 response rate was generally high and sustained through OLE2 Period Week 48. For study participants in Group B (interrupted treatment) bimekizumab 320mg Q8W (IGA <3 at Week 144/OLE2 Period Baseline), the PASI90 response rate increased through OLE2 Period Week 12 and was generally sustained through OLE2 Period Week 48, and rapidly regained IGA 0/1 response by OLE2 Period Week 12, and the IGA 0/1 response rate was generally high and sustained through OLE2 Period Week 48. For study participants in Group B (interrupted treatment) bimekizumab 320mg Q8W (IGA <3 at Week 144/OLE2 Period Baseline), the IGA 0/1 response rate increased through OLE2 Period Week 12 and was generally sustained through OLE2 Period Week 48. Cohort B: In study participants with plaque PSO, As early as Week 4, after a single dose of bimekizumab, the PASI90 response rate (NRI method) was 51.1% and increased to Week 16 (NRI method: 91.1%). The PASI90 response rate was generally sustained from Week 16 to Week 144 (NRI method: 73.3%, OC method: 86.88%). As early as Week 4, after a single dose of bimekizumab, the IGA 0/1 (with at least a 2 category improvement from Baseline) response rate was 37.8% (NRI method). The IGA 0/1 response rate increased from Week 4 to Week 16 (NRI method: 82.2%) and was generally sustained through to Week 144 (NRI method: 60.0%, OC method: 71.1%). In study participants with GPP, at Baseline, the mean JDA score was 3.3, which improved, as measured by mean change from Baseline JDA score at Week 16 (2.2) and improved further at Week 144 (2.8). At Week 16, 3/10 study participants (30.0%) had Very much improved, 5/10 study participants (50.0%) had Much improved, and 2/10 study participants (20.0%) had No change categories of the Global Improvement Score. At Week 144, 5/8 study participants (62.5%) had Very much improved and 3/8 study participants (37.5%) had much improved of the Global Improvement Score categories. The majority of study participants reported either improved CGI-I status or remission CGI-I status up to Week 36, and then all study participants reported either improved CGI I status or remission CGI-I status up to Week 144. One study participant reported a worsened CGI-I status at the Week 12 visit only. In study participants with EP, as early as Week 4, after a single dose of bimekizumab, the PASI90 response rate (OC method) was 3/11 study participants (27.3%), increased to 8/11 study participants (72.7%) at Week 16, and was sustained through Week 144 (9/10 study participants [90.0%]). After Week 4, all study participants reported either improved CGI-I status or remission CGI-I status at each visit except for 1 study participant who reported no change at both Week 132 and Week 144. No study participants had worsened CGI-I over the course of the study.

In Cohort A, considering both the safety and efficacy results, a positive benefit risk balance of open label bimekizumab treatment was observed over the 144-week Treatment Period in study participants with PSO in PS0014 following up to 1 year of bimekizumab treatment in the feeder studies. In Cohort B, considering both the safety and efficacy results, a positive benefit risk balance of bimekizumab treatment through 144 weeks in participants with PSO, GPP, and EP was observed.

May. 30, 2025

No

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

Oct. 10, 2018

Interventional

Multicenter, open-label study

treatment purpose

3

[Cohort A]
- Female subjects who plan to become pregnant during the study
- Subject has a positive or indeterminate IGRA in a feeder study, unless appropriately evaluated and treated

[Cohort B]
<For overall Cohort B>
- Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study
- Subject has guttate PSO or drug-induced PSO
- Subject has an active infection or history of infections
- Subject has known 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, PsA, GPP, or EP, including but not limited to rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, Crohn's disease, or ulcerative colitis
<For PSO>
- Subject has GPP or EP
- Subject has experienced primary failure (no response within 12 weeks) to 1 or more IL-17 biologic response modifier (eg, brodalumab, ixekizumab, secukinumab) OR more than 1 biologic response modifier other than an IL-17
<For GPP or EP>
- Subject has a differential diagnosis of the erythroderma (eg, erythroderma caused by lymphoma or drug eruption) other than EP
- Subject with a primary failure to any prior biologic therapy (primary failure defined as no response within the first 12 weeks of treatment with the biologic)

[Cohort A]
- Female subjects who plan to become pregnant during the study
- Subject has a positive or indeterminate IGRA in a feeder study, unless appropriately evaluated and treated

[Cohort B]
<For overall Cohort B>
- Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study
- Subject has guttate PSO or drug-induced PSO.
- Subject has an active infection or history of infections
- Subject has known 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, PsA, GPP, or EP, including but not limited to rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, Crohn's disease, or ulcerative colitis.
<For PSO>
- Subject has GPP or EP
- Subject has experienced primary failure (no response within 12 weeks) to 1 or more IL-17 biologic response modifier (eg, brodalumab, ixekizumab, secukinumab) OR more than 1 biologic response modifier other than an IL-17.
<For GPP or EP>
- Subject has a differential diagnosis of the erythroderma (eg, erythroderma caused by lymphoma or drug eruption) other than EP
- Subject with a primary failure to any prior biologic therapy (primary failure defined as no response within the first 12 weeks of treatment with the biologic).

Both

Psoriasis (Psoriasis, Psoriatic arthritis, Erythrodermic psoriasis, Generalized pustular psoriasis)

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 : bimekizumab (UCB4940) 320 mg will be administered subcutaneously every 4 weeks. After the symptom is stabilized, bimekizumab may be administered every 8 weeks.

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

safety
The incidence of TEAEs adjusted by duration of subject exposure to treatment

safety
efficacy
[Cohort A]
- Incidence of SAEs adjusted by duration of subject exposure to treatment
- Incidence of TEAEs leading to withdrawal adjusted by duration of subject exposure to treatment
- PASI90 at Week 144
- IGA response at Week 144

[Cohort B]
- PASI90 at Week 144
- IGA response at Week 144

+81-11-221-8807

July. 25, 2018