A Study to Evaluate the Efficacy and Safety of Bimekizumab Compared to Placebo and an Active Comparator in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis
- Conditions
- Moderate to Severe Chronic Plaque PsoriasisChronic Plaque PsoriasisPsoriatic Arthritis
- Interventions
- Registration Number
- NCT03370133
- Lead Sponsor
- UCB Biopharma SRL
- Brief Summary
This is a study to compare the efficacy of bimekizumab versus placebo and an active comparator in the treatment of subjects with moderate to severe chronic plaque psoriasis (PSO).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 567
- Must be at least 18 years of age
- Chronic plaque psoriasis (PSO) for at least 6 months prior to the Screening Visit
- Psoriasis Area Severity Index (PASI) >=12 and body surface area (BSA) affected by PSO >=10% and Investigator's Global Assessment (IGA) score >=3 on a 5-point scale
- Subject is a candidate for systemic PSO therapy and/or phototherapy
- Female subject of child bearing potential must be willing to use highly effective method of contraception
- Subject has an active infection (except common cold), a recent serious infection, or a history of opportunistic or recurrent chronic infections
- Subject has concurrent acute or chronic viral hepatitis B or C or human immunodeficiency virus (HIV) infection
- 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 any other condition, including medical or psychiatric, which, in the Investigator's judgment, would make the subject unsuitable for inclusion in the study
- Presence of active suicidal ideation or positive suicide behavior
- Presence of moderately severe major depression or severe major depression
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ustekinumab cohort Placebo Subjects will receive ustekinumab (dose 1 or dose 2 depending on subjects weight) for 52 weeks. Placebo will be administered at pre-specified time points to maintain the blinding. Placebo Placebo Subjects will receive placebo up to week 16 and bimekizumab starting at week 16 through week 52. Ustekinumab cohort Ustekinumab Subjects will receive ustekinumab (dose 1 or dose 2 depending on subjects weight) for 52 weeks. Placebo will be administered at pre-specified time points to maintain the blinding. Placebo Bimekizumab Subjects will receive placebo up to week 16 and bimekizumab starting at week 16 through week 52. Bimekizumab cohort Bimekizumab Subjects will receive bimekizumab for 52 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants With a Psoriasis Area and Severity Index 90 (PASI90) Response at Week 16 Week 16 The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This 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.
Percentage of Participants With an Investigator's Global Assessment (IGA) (Clear or Almost Clear With at Least a 2-category Improvement From Baseline) Response at Week 16 Week 16 The Investigator's Global Assessment (IGA) measures the overall psoriasis severity following a 5-point scale (0-4), where scale 0= clear, no signs of psoriasis; presence of post-inflammatory hyperpigmentation, scale 1= almost clear, no thickening; normal to pink coloration; no to minimal focal scaling, scale 2= mild thickening, pink to light red coloration and predominately fine scaling, 3= moderate, clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling and 4= severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. IGA response was defined as clear \[0\] or almost clear \[1\] with at least a two-category improvement from Baseline at Week 16.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With a Patient Symptom Diary Response for Pain at Week 16 Week 16 As Patient-Reported-Outcome (PRO) measure, the PSD (further published as P-SIM) was used to assess key symptoms relevant to patients with moderate to severe plaque psoriasis. Site staff trained participants on the use of the electronic device used to collect ePRO diary data at Screening, device was then dispensed to the participant for home use until Week 16 Visit. The ePRO diary was completed on daily basis from Screening to Week 16 Visit.
PSD pain item was assessed daily on a numeric rating scale (NRS) from 0 (no pain) to 10 (very severe pain). PSD score for pain at a given visit was an average of daily values over the week prior to the visit. The response was defined as an improvement (decrease) in pain score higher than the prespecified 1.98 response threshold at Week 16. The endpoint was characterized as percentage of participants with PSD pain response.Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to Study Treatment During the Initial Treatment Period From Baseline to end of Initial Treatment Period, including the Safety Follow-Up visit for those withdrawn from IMP (up to 36 weeks) The number of TEAEs leading to discontinuation adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used.
Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to Study Treatment During the Maintenance Treatment Period From Week 16 to Safety Follow-Up (up to 52 weeks duration) The number of SAEs adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used.
Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to Study Treatment During the Maintenance Treatment Period From Week 16 to Safety Follow-Up (up to 52 weeks duration) The number of TEAEs leading to discontinuation adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used.
Percentage of Participants With a PASI100 Response at Week 16 Week 16 The PASI100 response assessments are based on a 100% improvement in the PASI score from Baseline. This 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.
Percentage of Participants With a PASI75 Response at Week 4 Week 4 The PASI75 response assessments are based on at least 75% improvement in the PASI score from Baseline. This 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.
Percentage of Participants With a Patient Symptom Diary Response for Scaling at Week 16 Week 16 As PRO measure, the PSD (further published as P-SIM) was used to assess key symptoms relevant to patients with moderate to severe plaque psoriasis. Site staff trained participants on the use of the electronic device used to collect ePRO diary data at Screening, device was then dispensed to the participant for home use until Week 16 Visit. The ePRO diary was completed on daily basis from Screening to Week 16 Visit. PSD scaling item was assessed daily on a NRS from 0 (no scaling) to 10 (very severe scaling). PSD score for scaling was an average of daily values over the week prior to the visit. The response was defined as an improvement (decrease) in scaling score higher than the prespecified 2.86 response threshold at Week 16. The endpoint was characterized as percentage of participants with a PSD scaling response.
Percentage of Participants With an IGA 0 Response at Week 16 Week 16 The Investigator's Global Assessment (IGA) measures the overall psoriasis severity following a 5-point scale (0-4), where scale 0= clear, no signs of psoriasis; presence of post-inflammatory hyperpigmentation, scale 1= almost clear, no thickening; normal to pink coloration; no to minimal focal scaling, scale 2= mild thickening, pink to light red coloration and predominately fine scaling, 3= moderate, clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling and 4= severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. IGA response was defined as clear \[0\] with at least a two-category improvement from Baseline at Week 16.
Percentage of Participants With a Patient Symptom Diary Response for Itch at Week 16 Week 16 A PRO measure, the PSD (further published as P-SIM) was used to assess key symptoms relevant to patients with moderate to severe plaque psoriasis. Site staff trained participants on the use of the electronic device used to collect ePRO diary data at Screening, device was then dispensed to participant for home use until Week 16 Visit. The ePRO diary was completed on daily basis from Screening to Week 16 Visit.
PSD itch item was assessed daily on a NRS from 0 (no itch) to 10 (very severe itch). PSD score for itch was an average of daily values over the week prior to the visit. The response was defined as an improvement (decrease) in itch score higher than the prespecified 2.39 response threshold at Week 16. The endpoint was characterized as percentage of participants with a PSD itch response.Percentage of Participants With a PASI90 Response at Week 52 Week 52 The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This 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.
Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Study Treatment During the Initial Treatment Period From Baseline to end of Initial Treatment Period, including the Safety Follow-Up visit for those withdrawn from IMP (up to 36 weeks) The number of TEAEs adjusted by duration of exposure to study treatment was scaled such that provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the Adverse Event (AE) being considered. If a participant had no events, the total time at risk was used.
Percentage of Participants With a Scalp IGA Response (Clear or Almost Clear) at Week 16 for Participants With Scalp Psoriasis (PSO) >=2 at Baseline Week 16 Only participants with scalp involvement at Baseline completed the scalp IGA. Participants with scalp involvement at Baseline were defined as those with a scalp IGA score \>0 at Baseline. Scalp lesions were assessed in terms of clinical signs of redness, thickness, and scaliness using a 5-point scale (0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, 4= Severe). Scalp IGA 0/1 response at Week 16 was defined as clear (0) or almost clear (1) with at least a 2-category improvement from Baseline to Week 16.
Percentage of Participants With a PASI90 Response at Week 12 Week 12 The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This 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.
Percentage of Participants With an IGA (Clear or Almost Clear With at Least a 2-category Improvement From Baseline) Response at Week 12 Week 12 The Investigator's Global Assessment (IGA) measures the overall psoriasis severity following a 5-point scale (0-4), where scale 0= clear, no signs of psoriasis; presence of post-inflammatory hyperpigmentation, scale 1= almost clear, no thickening; normal to pink coloration; no to minimal focal scaling, scale 2= mild thickening, pink to light red coloration and predominately fine scaling, 3= moderate, clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling and 4= severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. IGA response was defined as clear \[0\] or almost clear \[1\] with at least a two-category improvement from Baseline at Week 12.
Percentage of Participants With an IGA (Clear or Almost Clear With at Least a 2-category Improvement From Baseline) Response at Week 52 Week 52 The Investigator's Global Assessment (IGA) measures the overall psoriasis severity following a 5-point scale (0-4), where scale 0= clear, no signs of psoriasis; presence of post-inflammatory hyperpigmentation, scale 1= almost clear, no thickening; normal to pink coloration; no to minimal focal scaling, scale 2= mild thickening, pink to light red coloration and predominately fine scaling, 3= moderate, clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling and 4= severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. IGA response was defined as clear \[0\] or almost clear \[1\] with at least a two-category improvement from Baseline at Week 52.
Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to Study Treatment During the Initial Treatment Period From Baseline to end of Initial Treatment Period, including the Safety Follow-Up visit for those withdrawn from IMP (up to 36 weeks) The number of SAEs adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used.
Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Study Treatment During the Maintenance Treatment Period From Week 16 to Safety Follow-Up (up to 52 weeks duration) The number of TEAEs adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the Adverse Event (AE) being considered. If a participant had no events, the total time at risk was used.
Trial Locations
- Locations (105)
Ps0009 253
🇭🇺Orosháza, Hungary
Ps0009 607
🇯🇵Chiyoda, Japan
Ps0009 620
🇯🇵Hamamatsu, Japan
Ps0009 608
🇯🇵Itabashi-Ku, Japan
Ps0009 624
🇯🇵Obihiro, Japan
Ps0009 614
🇯🇵Osaka, Japan
Ps0009 613
🇯🇵Shimotsuke, Japan
Ps0009 602
🇯🇵Shinagawa-Ku, Japan
Ps0009 612
🇯🇵Shinjuku-Ku, Japan
Ps0009 609
🇯🇵Kobe, Japan
Ps0009 611
🇯🇵Osaka, Japan
Ps0009 600
🇯🇵Kurume, Japan
Ps0009 622
🇯🇵Matsumoto, Japan
Ps0009 623
🇯🇵Morioka, Japan
Ps0009 621
🇯🇵Nagoya, Japan
Ps0009 369
🇵🇱Białystok, Poland
Ps0009 351
🇵🇱Warsaw, Poland
Ps0009 404
🇷🇺Saint Petersburg, Russian Federation
Ps0009 604
🇯🇵Minato-Ku, Japan
Ps0009 625
🇯🇵Nankoku, Japan
Ps0009 617
🇯🇵Sendai, Japan
Ps0009 618
🇯🇵Shinjuku-Ku, Japan
Ps0009 615
🇯🇵Sumida, Japan
Ps0009 606
🇯🇵Takaoka, Japan
Ps0009 350
🇵🇱Warsaw, Poland
Ps0009 367
🇵🇱Wrocław, Poland
Ps0009 362
🇵🇱Białystok, Poland
Ps0009 907
🇺🇸Miami, Florida, United States
Ps0009 924
🇺🇸Houston, Texas, United States
Ps0009 914
🇺🇸San Antonio, Texas, United States
Ps0009 553
🇬🇧Edgbaston, United Kingdom
Ps0009 550
🇬🇧Manchester, United Kingdom
Ps0009 921
🇺🇸Ormond Beach, Florida, United States
Ps0009 919
🇺🇸San Diego, California, United States
Ps0009 909
🇺🇸Boynton Beach, Florida, United States
Ps0009 912
🇺🇸Coral Gables, Florida, United States
Ps0009 906
🇺🇸Boca Raton, Florida, United States
Ps0009 918
🇺🇸Tampa, Florida, United States
Ps0009 941
🇺🇸Alpharetta, Georgia, United States
Ps0009 910
🇺🇸Bakersfield, California, United States
Ps0009 911
🇺🇸Plainfield, Indiana, United States
Ps0009 915
🇺🇸Saint Louis, Missouri, United States
Ps0009 903
🇺🇸Ocala, Florida, United States
Ps0009 900
🇺🇸West Des Moines, Iowa, United States
Ps0009 917
🇺🇸Troy, Michigan, United States
Ps0009 905
🇺🇸Overland Park, Kansas, United States
Ps0009 901
🇺🇸Portsmouth, New Hampshire, United States
Ps0009 650
🇨🇦Surrey, Canada
Ps0009 218
🇩🇪Bonn, Germany
Ps0009 920
🇺🇸Portland, Oregon, United States
Ps0009 004
🇦🇺Fremantle, Australia
Ps0009 005
🇦🇺Phillip, Australia
Ps0009 051
🇧🇪Loverval, Belgium
Ps0009 211
🇩🇪Hamburg, Germany
Ps0009 651
🇨🇦Richmond Hill, Canada
Ps0009 653
🇨🇦Toronto, Canada
Ps0009 657
🇨🇦Waterloo, Canada
Ps0009 210
🇩🇪Friedrichshafen, Germany
Ps0009 209
🇩🇪Darmstadt, Germany
Ps0009 208
🇩🇪Frankfurt/Main, Germany
Ps0009 300
🇮🇹Roma, Italy
Ps0009 303
🇮🇹Roma, Italy
Ps0009 255
🇭🇺Budapest, Hungary
Ps0009 213
🇩🇪Mahlow, Germany
Ps0009 212
🇩🇪Heidelberg, Germany
Ps0009 259
🇭🇺Szekszárd, Hungary
Ps0009 629
🇯🇵Asahikawa, Japan
Ps0009 605
🇯🇵Bunkyō-Ku, Japan
Ps0009 601
🇯🇵Fukuoka, Japan
Ps0009 627
🇯🇵Itabashi-Ku, Japan
Ps0009 217
🇩🇪Schweinfurt, Germany
Ps0009 254
🇭🇺Budapest, Hungary
Ps0009 610
🇯🇵Chuo Ku, Japan
Ps0009 619
🇯🇵Gifu, Japan
Ps0009 371
🇵🇱Bydgoszcz, Poland
Ps0009 603
🇯🇵Sapporo, Japan
Ps0009 628
🇯🇵Shinjuku-Ku, Japan
Ps0009 616
🇯🇵Tsu, Japan
Ps0009 358
🇵🇱Katowice, Poland
Ps0009 374
🇵🇱Poznań, Poland
Ps0009 402
🇷🇺Moscow, Russian Federation
Ps0009 403
🇷🇺Moscow, Russian Federation
Ps0009 357
🇵🇱Kielce, Poland
Ps0009 552
🇬🇧Liverpool, United Kingdom
Ps0009 400
🇷🇺Moscow, Russian Federation
Ps0009 370
🇵🇱Wrocław, Poland
Ps0009 372
🇵🇱Łódź, Poland
Ps0009 556
🇬🇧Cardiff, United Kingdom
Ps0009 551
🇬🇧Dundee, United Kingdom
Ps0009 555
🇬🇧Salford, United Kingdom
Ps0009 673
🇨🇦Halifax, Canada
Ps0009 652
🇨🇦Oakville, Canada
Ps0009 214
🇩🇪Erlangen, Germany
Ps0009 205
🇩🇪Osnabrück, Germany
Ps0009 923
🇺🇸Albuquerque, New Mexico, United States
Ps0009 009
🇦🇺Woolloongabba, Australia
Ps0009 908
🇺🇸East Windsor, New Jersey, United States
Ps0009 913
🇺🇸New York, New York, United States
Ps0009 002
🇦🇺Westmead, Australia
Ps0009 958
🇺🇸Omaha, Nebraska, United States
Ps0009 946
🇺🇸Phoenix, Arizona, United States
Ps0009 050
🇧🇪Bruxelles, Belgium
Ps0009 052
🇧🇪Liège, Belgium
Ps0009 922
🇺🇸Baton Rouge, Louisiana, United States
Ps0009 626
🇯🇵Shinjuku-Ku, Japan