A Study With a Initial Treatment Period Followed by a Randomized-withdrawal Period to Evaluate the Efficacy and Safety of Bimekizumab in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis
- Conditions
- Moderate to Severe Chronic Plaque PsoriasisPsoriatic ArthritisChronic Plaque Psoriasis
- Interventions
- Other: Placebo
- Registration Number
- NCT03410992
- Lead Sponsor
- UCB Biopharma SRL
- Brief Summary
Phase 3 study to compare the efficacy of bimekizumab versus placebo in the treatment of subjects with moderate to severe chronic plaque psoriasis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 435
- 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, recurrent, or 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 Placebo Placebo Subjects will receive placebo for 16 Weeks. Subjects who achieve certain predefined response criteria will proceed with placebo until Week 56. Subjects who do not achieve certain predefined response criteria will enter the bimekizumab escape arm. Bimekizumab cohort Placebo Subjects will receive bimekizumab for 16 Weeks. Subjects who achieve certain predefined response criteria will be re-randomized to either receive bimekizumab or placebo until Week 56. Subjects who do not achieve predefined response criteria will enter the bimekizumab escape arm. Bimekizumab Escape arm Bimekizumab Subjects who do not achieve certain predefined response criteria at Week 16 or later will enter the bimekizumab escape arm and will receive open-label bimekizumab for 12 weeks. Bimekizumab cohort Bimekizumab Subjects will receive bimekizumab for 16 Weeks. Subjects who achieve certain predefined response criteria will be re-randomized to either receive bimekizumab or placebo until Week 56. Subjects who do not achieve predefined response criteria will enter the bimekizumab escape arm.
- Primary Outcome Measures
Name Time Method Percentage of Participants With a Psoriasis Area and Severity Index 90 (PASI90) Response at Week 16 At Week 16 A PASI90 responder was defined as a participant that achieved 90% reduction from Baseline in the PASI score. Body divided into 4 areas: head/arms/trunk to groin/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)-4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0-6 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 min possible PASI score is 0=no disease, the max score is 72=maximal disease. Study participants with missing score at Week 16 were counted as nonresponders (NRI).
Percentage of Participants With an Investigator's Global Assessment (IGA) Response at Week 16 At 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 or Almost Clear with at least a 2-category improvement relative to Baseline. Study participants with missing score at Week 16 were counted as nonresponders (NRI).
- Secondary Outcome Measures
Name Time Method Percentage of Participants With a IGA Clear Response at Week 16 At 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 with at least \>= 2 category improvement relative to Baseline. Study participants with missing score at Week 16 were counted as nonresponders (NRI).
Percentage of Participants With a Patient Symptom Diary Response for Scaling at Week 16 At 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 a PASI90 Response at Week 56 Among Week 16 PASI90 Responders At Week 56 A PASI90 responder was defined as a participant that achieved 90% reduction from Baseline in the PASI score. Study participants with missing score at Week 56 or who met the criterion for relapse were counted as nonresponders (NRI).
Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period From end of Initial Treatment Period (Week 16) until the Safety Follow-Up (up to 56 weeks duration) The number of SAEs adjusted by duration of exposure to study treatment was scaled such that it provides 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 Participant Exposure to Study Treatment During the Randomized-Withdrawal Period From end of Initial Treatment Period (Week 16) until the Safety Follow-Up (up to 56 weeks duration) The number of TEAEs leading to discontinuation adjusted by duration of exposure to study treatment was scaled such that it provides 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 Participant Exposure to Study Treatment During the Escape Treatment From Escape Baseline (Week 0) until Safety Follow-Up (up to 28 weeks duration) The number of SAEs adjusted by duration of exposure to study treatment was scaled such that it provides 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 PASI75 Response at Week 4 At Week 4 A PASI75 responder was defined as a participant that achieved 75% reduction from Baseline in the PASI score. Body divided into 4 areas: head/arms/trunk to groin/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)-4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0-6 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 min possible PASI score is 0=no disease, the max score is 72=maximal disease. Study participants with missing score at a given week were counted as nonresponders.
Percentage of Participants With a Patient Symptom Diary Response for Itch at Week 16 At 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.Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Initial Treatment Period From Baseline to end of Initial Treatment Period (up to Week 16) The number of TEAEs adjusted by duration of exposure to study treatment was scaled such that it provides 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.
Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Initial Treatment Period From Baseline to end of Initial Treatment Period (up to Week 16) The number of SAEs adjusted by duration of exposure to study treatment was scaled such that it provides 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 Participant Exposure to Study Treatment During the Initial Treatment Period From Baseline to end of Initial Treatment Period (up to Week 16) The number of TEAEs leading to discontinuation adjusted by duration of exposure to study treatment was scaled such that it provides 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 Participant Exposure to Study Treatment During the Randomized-Withdrawal Period From end of Initial Treatment Period (Week 16) until the Safety Follow-Up (up to 56 weeks duration) The number of TEAEs adjusted by duration of exposure to study treatment was scaled such that it provides 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 PASI100 Response at Week 16 At Week 16 A PASI100 responder was defined as a participant that achieved 100% reduction from Baseline in the PASI score. Body divided into 4 areas: head/arms/trunk to groin/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)-4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0-6 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 min possible PASI score is 0=no disease, the max score is 72=maximal disease. Study participants with missing score at Week 16 were counted as nonresponders (NRI).
Percentage of Participants With a Patient Symptom Diary Response for Pain at Week 16 At 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 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.Percentage of Participants With Scalp IGA Response (Clear or Almost Clear) at Week 16 for Participants With Scalp Psoriasis (PSO) at Baseline At 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.
Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment From Escape Baseline (Week 0) until Safety Follow-Up (up to 28 weeks duration) The number of TEAEs adjusted by duration of exposure to study treatment was scaled such that it provides 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.
Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment From Escape Baseline (Week 0) until Safety Follow-Up (up to 28 weeks duration) The number of TEAEs leading to discontinuation adjusted by duration of exposure to study treatment was scaled such that it provides 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.
Trial Locations
- Locations (77)
Ps0013 361
🇵🇱Białystok, Poland
Ps0013 402
🇷🇺Moscow, Russian Federation
Ps0013 359
🇵🇱Katowice, Poland
Ps0013 357
🇵🇱Kielce, Poland
Ps0013 351
🇵🇱Warsaw, Poland
Ps0013 354
🇵🇱Warszawa, Poland
Ps0013 360
🇵🇱Łódź, Poland
Ps0013 374
🇵🇱Poznań, Poland
Ps0013 350
🇵🇱Warsaw, Poland
Ps0013 368
🇵🇱Wrocław, Poland
Ps0013 403
🇷🇺Moscow, Russian Federation
Ps0013 962
🇺🇸Owensboro, Kentucky, United States
Ps0013 919
🇺🇸San Diego, California, United States
Ps0013 956
🇺🇸Verona, New Jersey, United States
Ps0013 967
🇺🇸Santa Monica, California, United States
Ps0013 966
🇺🇸Sandy Springs, Georgia, United States
Ps0013 928
🇺🇸Fort Myers, Florida, United States
Ps0013 954
🇺🇸Skokie, Illinois, United States
Ps0013 949
🇺🇸Cleveland, Ohio, United States
Ps0013 658
🇨🇦Ajax, Canada
Ps0013 672
🇨🇦Edmonton, Canada
Ps0013 675
🇨🇦Markham, Canada
Ps0013 668
🇨🇦North Bay, Canada
Ps0013 963
🇺🇸Rochester, New York, United States
Ps0013 008
🇦🇺East Melbourne, Australia
Ps0013 940
🇺🇸Beverly, Massachusetts, United States
Ps0013 937
🇺🇸Johnston, Rhode Island, United States
Ps0013 933
🇺🇸Murray, Utah, United States
Ps0013 968
🇺🇸New York, New York, United States
Ps0013 914
🇺🇸San Antonio, Texas, United States
Ps0013 006
🇦🇺Kogarah, Australia
Ps0013 202
🇩🇪Hamburg, Germany
Ps0013 003
🇦🇺Carlton, Australia
Ps0013 667
🇨🇦Ottawa, Canada
Ps0013 219
🇩🇪Münster, Germany
Ps0013 660
🇨🇦Montréal, Canada
Ps0013 665
🇨🇦Québec, Canada
Ps0013 676
🇨🇦Surrey, Canada
Ps0013 703
🇰🇷Seoul, Korea, Republic of
Ps0013 204
🇩🇪Witten, Germany
Ps0013 253
🇭🇺Orosháza, Hungary
Ps0013 671
🇨🇦Hamilton, Canada
Ps0013 220
🇩🇪Hamburg, Germany
Ps0013 200
🇩🇪Schwerin, Germany
Ps0013 262
🇭🇺Miskolc, Hungary
Ps0013 701
🇰🇷Busan, Korea, Republic of
Ps0013 352
🇵🇱Gdańsk, Poland
Ps0013 358
🇵🇱Katowice, Poland
Ps0013 363
🇵🇱Kraków, Poland
Ps0013 353
🇵🇱Szczecin, Poland
Ps0013 554
🇬🇧Reading, United Kingdom
Ps0013 550
🇬🇧Manchester, United Kingdom
Ps0013 365
🇵🇱Wrocław, Poland
Ps0013 370
🇵🇱Wrocław, Poland
Ps0013 401
🇷🇺Saratov, Russian Federation
Ps0013 406
🇷🇺Yaroslavl, Russian Federation
Ps0013 404
🇷🇺Saint Petersburg, Russian Federation
Ps0013 555
🇬🇧Salford, United Kingdom
Ps0013 663
🇨🇦Mississauga, Canada
Ps0013 657
🇨🇦Waterloo, Canada
Ps0013 705
🇰🇷Seongnam-si, Korea, Republic of
Ps0013 955
🇺🇸San Diego, California, United States
Ps0013 965
🇺🇸New York, New York, United States
Ps0013 901
🇺🇸Portsmouth, New Hampshire, United States
Ps0013 944
🇺🇸New Orleans, Louisiana, United States
Ps0013 947
🇺🇸Buffalo, New York, United States
Ps0013 400
🇷🇺Moscow, Russian Federation
Ps0013 405
🇷🇺Saint Petersburg, Russian Federation
Ps0013 369
🇵🇱Białystok, Poland
Ps0013 366
🇵🇱Katowice, Poland
Ps0013 356
🇵🇱Lublin, Poland
Ps0013 258
🇭🇺Veszprém, Hungary
Ps0013 929
🇺🇸Portland, Oregon, United States
Ps0013 260
🇭🇺Szeged, Hungary
Ps0013 250
🇭🇺Szolnok, Hungary
Ps0013 261
🇭🇺Budapest, Hungary
Ps0013 355
🇵🇱Białystok, Poland