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

Study Overview
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Brief Summary
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Phase 3 study to compare the efficacy of bimekizumab versus placebo in the treatment of subjects with moderate to severe chronic plaque psoriasis.

Official Title
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A Phase 3, Multicenter, Double-Blind, Placebo-Controlled Study With an 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
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Chronic Plaque Psoriasis, Moderate to Severe Chronic Plaque Psoriasis, Psoriatic Arthritis

Intervention / Treatment
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* Drug: Bimekizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bimekizumab cohort<br>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. | Drug: Bimekizumab<br>* Bimekizumab will be provided at pre-specified time intervals.<br>* Other names: UCB4940;Other: Placebo<br>* Subjects will receive Placebo at pre-specified time points to maintain the blinding of the Investigational Medicinal Products.<br>* Other names: PBO;|
| Placebo Comparator: Placebo<br>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. | Other: Placebo<br>* Subjects will receive Placebo at pre-specified time points to maintain the blinding of the Investigational Medicinal Products.<br>* Other names: PBO;|
| Experimental: Bimekizumab Escape arm<br>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. | Drug: Bimekizumab<br>* Bimekizumab will be provided at pre-specified time intervals.<br>* Other names: UCB4940;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Psoriasis Area and Severity Index 90 (PASI90) Response 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). | At Week 16 | 
| Percentage of Participants With an Investigator's Global Assessment (IGA) Response 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). | At Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a PASI100 Response 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). | At Week 16 | 
| Percentage of Participants With a IGA Clear Response 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). | At Week 16 | 
| Percentage of Participants With a PASI75 Response 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. | At Week 4 | 
| Percentage of Participants With a Patient Symptom Diary Response for Pain 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. | At Week 16 | 
| Percentage of Participants With a Patient Symptom Diary Response for Itch 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. | At Week 16 | 
| Percentage of Participants With a Patient Symptom Diary Response for Scaling 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. | At Week 16 | 
| Percentage of Participants With Scalp IGA Response (Clear or Almost Clear) at Week 16 for Participants With Scalp Psoriasis (PSO) at Baseline | 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. | At Week 16 | 
| Percentage of Participants With a PASI90 Response at Week 56 Among Week 16 PASI90 Responders | 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). | At Week 56 | 
| Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Initial Treatment Period | 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. | From Baseline to end of Initial Treatment Period (up to Week 16) | 
| Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Initial Treatment Period | 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. | From Baseline to end of Initial Treatment Period (up to Week 16) | 
| Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Initial Treatment Period | 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. | From Baseline to end of Initial Treatment Period (up to Week 16) | 
| Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 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. | From end of Initial Treatment Period (Week 16) until the Safety Follow-Up (up to 56 weeks duration) | 
| Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 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. | From end of Initial Treatment Period (Week 16) until the Safety Follow-Up (up to 56 weeks duration) | 
| Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 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. | From end of Initial Treatment Period (Week 16) until the Safety Follow-Up (up to 56 weeks duration) | 
| Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 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. | From Escape Baseline (Week 0) until Safety Follow-Up (up to 28 weeks duration) | 
| Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 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. | From Escape Baseline (Week 0) until Safety Follow-Up (up to 28 weeks duration) | 
| Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 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. | From Escape Baseline (Week 0) until Safety Follow-Up (up to 28 weeks duration) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bimekizumab, PSO, Psoriasis