Chronic Plaque Psoriasis, Moderate to Severe Chronic Plaque Psoriasis, Psoriatic Arthritis
Conditions
Keywords
Bimekizumab, PSO, Psoriasis
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.
Interventions
DRUGBimekizumab
Bimekizumab will be provided at pre-specified time intervals.
OTHERPlacebo
Subjects will receive Placebo at pre-specified time points to maintain the blinding of the Investigational Medicinal Products.
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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 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. |
| 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 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. |
| 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 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. |
| 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 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 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. |
| 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. |
Countries
Australia, Canada, Germany, Hungary, Poland, Russia, South Korea, United Kingdom, United States
Contacts
STUDY_DIRECTORUCB Cares
001 844 599 2273 (UCB)
Participant flow
Recruitment details
The study started to enroll patients in February 2018 and concluded in January 2020.
Pre-assignment details
Study has a 2-5 weeks Screening Period, a 16 weeks Initial Period, a 40 weeks Randomized-Withdrawal Period (RWP) and a SFU Period (20 weeks after final dose). Participants who did not achieve a PASI90 response at Wk16 or who relapsed at Wk20/later during the RWP, entered 12 weeks of escape treatment. Participant Flow refers to the Randomized Set.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo for 16 weeks. Participants who achieved a Psoriasis Area Severity Index (PASI) 90 response criteria proceeded with placebo until Week 56. Participants who did not achieve a PASI90 response criteria at Week 16 or who relapsed at Week 20 or later, entered the escape arm and received open-label bimekizumab 320 mg Q4W for 12 weeks. | 86 |
| Bimekizumab 320 mg Q4W Participants received bimekizumab 320 mg Q4W for 16 weeks. Participants who achieved a PASI90 response criteria were re-randomized to either receive bimekizumab 320 mg Q4W or bimekizumab 320 mg Q8W or placebo until Week 56. Participants who did not achieve a PASI90 response criteria at Week 16 or who relapsed at Week 20 or later, entered the escape arm and received open-label bimekizumab 320 mg Q4W for 12 weeks. | 349 |
| Total Title | 435 |
| Total | 870 |
Baseline characteristics
| Characteristic | Placebo | Bimekizumab 320 mg Q4W | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical >=65 years | 4 Participants | 21 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 80 Participants | 327 Participants | 407 Participants |
| Age, Continuous | 43.5 years STANDARD_DEVIATION 13.1 | 44.5 years STANDARD_DEVIATION 12.9 | 44.3 years STANDARD_DEVIATION 12.9 |
| Race/Ethnicity, Customized Asian | 5 Participants | 13 Participants | 18 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Other/mixed | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 79 Participants | 324 Participants | 403 Participants |
| Sex: Female, Male Female | 28 Participants | 94 Participants | 122 Participants |
| Sex: Female, Male Male | 58 Participants | 255 Participants | 313 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 86 | 0 / 349 | 0 / 1 | 0 / 105 | 0 / 100 | 0 / 106 | 0 / 81 | 0 / 23 | 0 / 67 | 0 / 4 | 0 / 7 |
| other Total, other adverse events | 15 / 86 | 66 / 349 | 1 / 1 | 34 / 105 | 40 / 100 | 34 / 106 | 8 / 81 | 5 / 23 | 11 / 67 | 3 / 4 | 4 / 7 |
| serious Total, serious adverse events | 2 / 86 | 6 / 349 | 0 / 1 | 4 / 105 | 3 / 100 | 5 / 106 | 1 / 81 | 0 / 23 | 0 / 67 | 0 / 4 | 0 / 7 |
Outcome results
Primary
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).
Time frame: At Week 16
Population: e Randomized Set (RS) consisted of all randomized study participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Percentage of Participants With an Investigator's Global Assessment (IGA) Response at Week 16 | 1.2 percentage of participants |
| Bimekizumab 320 mg Q4W (RS) | Percentage of Participants With an Investigator's Global Assessment (IGA) Response at Week 16 | 92.6 percentage of participants |
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.p-value: <0.00195% CI: [105.792, 4083.333]Cochran-Mantel-Haenszel
Primary
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).
Time frame: At Week 16
Population: The Randomized Set (RS) consisted of all randomized study participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Percentage of Participants With a Psoriasis Area and Severity Index 90 (PASI90) Response at Week 16 | 1.2 percentage of participants |
| Bimekizumab 320 mg Q4W (RS) | Percentage of Participants With a Psoriasis Area and Severity Index 90 (PASI90) Response at Week 16 | 90.8 percentage of participants |
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.p-value: <0.00195% CI: [82.798, 2975.086]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: From Escape Baseline (Week 0) until Safety Follow-Up (up to 28 weeks duration)
Population: The ESS consisted of all study participants who received at least 1 dose of escape bimekizumab treatment either due to not achieving a PASI90 response at Week 16 or experiencing a relapse after entering the Randomized-Withdrawal Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 5.24 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W (RS) | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 0 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q4W (WK16ResS) | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 0 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q8W+Q4W/Q4W (WK16ResS) | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 0 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q4W Escape (ESS) | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 0 no. of new events per 100 subject-years |
Secondary
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.
Time frame: From Baseline to end of Initial Treatment Period (up to Week 16)
Population: The Safety Set (SS) consisted of all study participants who received at least 1 dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Initial Treatment Period | 7.66 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W (RS) | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Initial Treatment Period | 5.59 no. of new events per 100 subject-years |
Secondary
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.
Time frame: From end of Initial Treatment Period (Week 16) until the Safety Follow-Up (up to 56 weeks duration)
Population: The Week 16 Responder Set (WK16ResS) consisted of all study participants who achieved a PASI90 response at Week 16 and received at least 1 dose of the IMP during the Randomized-Withdrawal Period at Week 16 or later.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 0 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W (RS) | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 7.20 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q4W (WK16ResS) | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 4.04 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q8W+Q4W/Q4W (WK16ResS) | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 6.64 no. of new events per 100 subject-years |
Secondary
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.
Time frame: From Escape Baseline (Week 0) until Safety Follow-Up (up to 28 weeks duration)
Population: The ESS consisted of all study participants who received at least 1 dose of escape bimekizumab treatment either due to not achieving a PASI90 response at Week 16 or experiencing a relapse after entering the Randomized-Withdrawal Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 0 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W (RS) | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 18.77 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q4W (WK16ResS) | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 0 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q8W+Q4W/Q4W (WK16ResS) | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 0 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q4W Escape (ESS) | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 0 no. of new events per 100 subject-years |
Secondary
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.
Time frame: From Baseline to end of Initial Treatment Period (up to Week 16)
Population: The Safety Set (SS) consisted of all study participants who received at least 1 dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Initial Treatment Period | 0 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W (RS) | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Initial Treatment Period | 2.78 no. of new events per 100 subject-years |
Secondary
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.
Time frame: From end of Initial Treatment Period (Week 16) until the Safety Follow-Up (up to 56 weeks duration)
Population: The Week 16 Responder Set (WK16ResS) consisted of all study participants who achieved a PASI90 response at Week 16 and received at least 1 dose of the IMP during the Randomized-Withdrawal Period at Week 16 or later.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 0 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W (RS) | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 5.33 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q4W (WK16ResS) | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 2.69 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q8W+Q4W/Q4W (WK16ResS) | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 0 no. of new events per 100 subject-years |
Secondary
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.
Time frame: From Escape Baseline (Week 0) until Safety Follow-Up (up to 28 weeks duration)
Population: The Escape Study Participant Set (ESS) consisted of all study participants who received at least 1 dose of escape bimekizumab treatment either due to not achieving a PASI90 response at Week 16 or experiencing a relapse after entering the Randomized-Withdrawal Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 235.86 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W (RS) | Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 287.19 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q4W (WK16ResS) | Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 180.89 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q8W+Q4W/Q4W (WK16ResS) | Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 491.37 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q4W Escape (ESS) | Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Escape Treatment | 349.52 no. of new events per 100 subject-years |
Secondary
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.
Time frame: From Baseline to end of Initial Treatment Period (up to Week 16)
Population: The Safety Set (SS) consisted of all study participants who received at least 1 dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Initial Treatment Period | 177.38 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W (RS) | Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Initial Treatment Period | 323.61 no. of new events per 100 subject-years |
Secondary
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.
Time frame: From end of Initial Treatment Period (Week 16) until the Safety Follow-Up (up to 56 weeks duration)
Population: The Week 16 Responder Set (WK16ResS) consisted of all study participants who achieved a PASI90 response at Week 16 and received at least 1 dose of the IMP during the Randomized-Withdrawal Period at Week 16 or later.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 144.37 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W (RS) | Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 242.11 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q4W (WK16ResS) | Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 224.87 no. of new events per 100 subject-years |
| Bimekizumab 320 mg Q4W/Q8W+Q4W/Q4W (WK16ResS) | Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment During the Randomized-Withdrawal Period | 208.88 no. of new events per 100 subject-years |
Secondary
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).
Time frame: At Week 16
Population: The Randomized Set (RS) consisted of all randomized study participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Percentage of Participants With a IGA Clear Response at Week 16 | 1.2 percentage of participants |
| Bimekizumab 320 mg Q4W (RS) | Percentage of Participants With a IGA Clear Response at Week 16 | 69.6 percentage of participants |
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.p-value: <0.00195% CI: [30.13, 1676.425]Cochran-Mantel-Haenszel
Secondary
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).
Time frame: At Week 16
Population: The Randomized Set (RS) consisted of all randomized study participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Percentage of Participants With a PASI100 Response at Week 16 | 1.2 percentage of participants |
| Bimekizumab 320 mg Q4W (RS) | Percentage of Participants With a PASI100 Response at Week 16 | 68.2 percentage of participants |
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.p-value: <0.00195% CI: [28.757, 1683.639]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: At Week 4
Population: The Randomized Set (RS) consisted of all randomized study participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Percentage of Participants With a PASI75 Response at Week 4 | 1.2 percentage of participants |
| Bimekizumab 320 mg Q4W (RS) | Percentage of Participants With a PASI75 Response at Week 4 | 75.9 percentage of participants |
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.p-value: <0.00195% CI: [39.423, 2543.254]Cochran-Mantel-Haenszel
Secondary
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).
Time frame: At Week 56
Population: The Week 16 Responder Set (WK16ResS) consisted of all study participants who achieved a PASI90 response at Week 16 and received at least 1 dose of IMP during Randomized-Withdrawal Period at Week 16 or later. The hypothesis test for PASI90 at Week 56, based on Wk16ResS, compared pooled BKZ regimens (BKZ 320mg Q4W/Q8W + 320mg Q4W/Q4W) versus placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Percentage of Participants With a PASI90 Response at Week 56 Among Week 16 PASI90 Responders | 16.2 percentage of participants |
| Bimekizumab 320 mg Q4W (RS) | Percentage of Participants With a PASI90 Response at Week 56 Among Week 16 PASI90 Responders | 91.0 percentage of participants |
| Bimekizumab 320 mg Q4W/Q4W (WK16ResS) | Percentage of Participants With a PASI90 Response at Week 56 Among Week 16 PASI90 Responders | 86.8 percentage of participants |
| Bimekizumab 320 mg Q4W/Q8W+Q4W/Q4W (WK16ResS) | Percentage of Participants With a PASI90 Response at Week 56 Among Week 16 PASI90 Responders | 88.8 percentage of participants |
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables. This statistical analysis is not controlled for multiplicity and is only nominal.p-value: <0.00195% CI: [18.622, 109.672]Cochran-Mantel-Haenszel
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables. This statistical analysis is not controlled for multiplicity and is only nominal.p-value: <0.00195% CI: [18.887, 128.673]Cochran-Mantel-Haenszel
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables. This statistical analysis is not controlled for multiplicity and is only nominal.p-value: <0.00195% CI: [22.087, 101.75]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: At Week 16
Population: The RS consisted of all randomized participants. Number of participants analyzed reflect those with a Baseline score at or above the 2.39 response threshold.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Percentage of Participants With a Patient Symptom Diary Response for Itch at Week 16 | 5.6 percentage of participants |
| Bimekizumab 320 mg Q4W (RS) | Percentage of Participants With a Patient Symptom Diary Response for Itch at Week 16 | 75.5 percentage of participants |
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.p-value: <0.00195% CI: [15.728, 120.295]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: At Week 16
Population: The RS consisted of all randomized participants. Number of participants analyzed reflect those with a Baseline score at or above the 1.98 response threshold.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Percentage of Participants With a Patient Symptom Diary Response for Pain at Week 16 | 9.0 percentage of participants |
| Bimekizumab 320 mg Q4W (RS) | Percentage of Participants With a Patient Symptom Diary Response for Pain at Week 16 | 78.8 percentage of participants |
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.p-value: <0.00195% CI: [14.22, 82.856]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: At Week 16
Population: The RS consisted of all randomized participants. Number of participants analyzed reflect those with a Baseline score at or above the 2.86 response threshold.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Percentage of Participants With a Patient Symptom Diary Response for Scaling at Week 16 | 5.7 percentage of participants |
| Bimekizumab 320 mg Q4W (RS) | Percentage of Participants With a Patient Symptom Diary Response for Scaling at Week 16 | 78.0 percentage of participants |
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haensze (CMH) test with region and prior biologic exposure as stratification variables.p-value: <0.00195% CI: [20.56, 180.669]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: At Week 16
Population: The Randomized Set (RS) consisted of all randomized study participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (RS) | Percentage of Participants With Scalp IGA Response (Clear or Almost Clear) at Week 16 for Participants With Scalp Psoriasis (PSO) at Baseline | 6.8 percentage of participants |
| Bimekizumab 320 mg Q4W (RS) | Percentage of Participants With Scalp IGA Response (Clear or Almost Clear) at Week 16 for Participants With Scalp Psoriasis (PSO) at Baseline | 92.3 percentage of participants |
Comparison: Odds ratio: Bimekizumab/Placebo calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.p-value: <0.00195% CI: [49.263, 506.745]Cochran-Mantel-Haenszel