A Study to Evaluate the Long-term Safety, Tolerability and Efficacy of Bimekizumab in Adult Patients With Chronic Plaque Psoriasis

Study Overview
=================
Brief Summary
-----------------
This is a study to assess the long-term safety, tolerability, and efficacy of bimekizumab.

Official Title
-----------------
A Multicenter, 48-week, Open-label Extension Study to Assess the Long-term Safety, Tolerability, and Efficacy of Bimekizumab in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis.

Conditions
-----------------
Chronic Plaque Psoriasis

Intervention / Treatment
-----------------
* Drug: Bimekizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject must have completed all dosing requirements in PS0016 without meeting any withdrawal criteria Female subjects must be postmenopausal, permanently sterilized or, if of childbearing potential, must be willing to use a highly effective method of contraception up till 20 weeks after last administration of study drug, and have a negative pregnancy test at Visit 1 (Screening) and immediately prior to first dose Male subjects with a partner of childbearing potential must be willing to use a condom when sexually active, up till 20 weeks after the last administration of study medication (anticipated 5 half-lives) Exclusion Criteria: Subjects previously participating in this study Subject has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the subject's ability to participate in this study. Note: For any subject with an ongoing serious adverse event (SAE), or a history of serious infections (including herpes zoster or hospitalizations) in PS0016, the Medical Monitor must be consulted prior to the subject's entry into PS0018 Subject has any current sign or symptom that may indicate a medically significant infection Subject has current clinically active infection with Histoplasma, Coccidiodes, Paracoccidioides, Pneumocystis, tuberculosis (TB), nontuberculous mycobacteria (NTMB),Blastomyces, Aspergillus, or Candidiasis (systemic). Any subject diagnosed with Histoplasmosis, Coccidiodes, Paracoccidioides, Pneumocystis, TB, NTMB, Blastomyces, Aspergillus, or Candidiasis (systemic) during PS0016 is excluded from PS0018 even if treatment has been completed. Any subject who meets any withdrawal criteria in the feeder study (PS0016) is excluded from participating in the open-label extension study (PS0018)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Subjects in this cohort will receive dose 1 every four weeks (Q4W) subcutaneously (sc) during the 48-week open-label Treatment Period. There will be an option to increase the dose to dose 2 Q4W at the discretion of the Investigator if the subject's Psoriasis Area and Severity Index (PASI) response is >=50% to <75% reduction from the Baseline of PS0016 at Week 12 or later. If the subject's disease is adequately controlled on dose 2 Q4W, they may return to dose 1 Q4W at the discretion of the Investigator. | Drug: Bimekizumab<br>* Bimekizumab will be administered subcutaneously in 2 different doses.<br>* Other names: UCB4940;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Event (TEAE) Adjusted by Duration of Participant Exposure to Treatment | TEAEs were events that had a start date on or after the first administration of study treatment in PS0018 until the last received dose of investigational medicinal product (IMP) +140 days [which covered the 20-week Safety Follow-Up (SFU) Visit]. 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 (Week 0) until Safety Follow Up Visit (up to Week 64) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of Bimekizumab During the Study | Plasma concentration of Bimekizumab was expressed in micrograms per milliliter (μg/mL). Values Below Limit of Quantification (BLQ) were replaced by value of Lower Limit of Quantification (LLOQ) divided by 2 (=0.075 μg/mL) in calculations of Means and Coefficient of Variations (CVs). Means and CVs were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint. | From Baseline (Week 0) until Safety Follow Up Visit (up to Week 64) | 
| Percentage of Participants With Positive Anti-bimekizumab (BZK) Antibody Levels Prior to Study Treatment | For a given visit / time point, an Anti-BKZ status of positive was concluded for any participant with an anti-drug antibody (ADA) level that was above cut point (ACP) and CP at that visit/ time point. A participant was classified as overall positive if at least one PS0018 measurement is ACP and CP (this included participants who had negative results at PS0016 Baseline). Percentages were based on the number of participants with a non-missing measurement, from samples that did not contain BKZ concentration levels above the drug tolerance, at the visit. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | Baseline of study PS0016 [NCT03025542] | 
| Percentage of Participants With Overall Positive Anti-bimekizumab (BZK) Antibody Levels Following Study Treatment | For a given visit / time point, an Anti-BKZ status of positive was concluded for any participant with an anti-drug antibody (ADA) level that was above cut point (ACP) and CP at that visit/ time point. A participant was classified as overall positive if at least one PS0018 measurement is ACP and CP (this included participants who had negative results at PS0016 Baseline). Percentages were based on the number of participants with a non-missing measurement, from samples that did not contain BKZ concentration levels above the drug tolerance, at the visit. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Achieving a 50% or Higher Improvement in Psoriasis Area and Severity Index (PASI) During the Study | The PASI quantifies the severity and extent of the disease and weighs these with the percentage of body surface area (BSA) involvement. The degree of involvement is estimated across 4 body areas; head, upper limbs, trunk, and lower limbs and then transferred into a grade. The Investigator assessed the average redness, thickness, and scaliness of lesions in each body area (each on a 5 - point scale); 0 = none, 1 = slight, 2 = moderate, 3 = marked, and 4 = very marked. The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity. The PASI50 responses were based on at least 50% improvement in the PASI score at the Baseline of PS0016. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Achieving a 75% or Higher Improvement in Psoriasis Area and Severity Index (PASI) During the Study | The PASI quantifies the severity and extent of the disease and weighs these with the percentage of body surface area (BSA) involvement. The degree of involvement is estimated across 4 body areas; head, upper limbs, trunk, and lower limbs and then transferred into a grade. The Investigator assessed the average redness, thickness, and scaliness of lesions in each body area (each on a 5 - point scale); 0 = none, 1 = slight, 2 = moderate, 3 = marked, and 4 = very marked. The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity. The PASI75 responses were based on at least 75% improvement in the PASI score at the Baseline of PS0016. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Achieving a 90% or Higher Improvement in Psoriasis Area and Severity Index (PASI) During the Study | The PASI quantifies the severity and extent of the disease and weighs these with the percentage of body surface area (BSA) involvement. The degree of involvement is estimated across 4 body areas; head, upper limbs, trunk, and lower limbs and then transferred into a grade. The Investigator assessed the average redness, thickness, and scaliness of lesions in each body area (each on a 5 - point scale); 0 = none, 1 = slight, 2 = moderate, 3 = marked, and 4 = very marked. The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity. The PASI90 responses were based on at least 90% improvement in the PASI score at the Baseline of PS0016. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Achieving a 100% Improvement in Psoriasis Area and Severity Index (PASI) During the Study | The PASI quantifies the severity and extent of the disease and weighs these with the percentage of body surface area (BSA) involvement. The degree of involvement is estimated across 4 body areas; head, upper limbs, trunk, and lower limbs and then transferred into a grade. The Investigator assessed the average redness, thickness, and scaliness of lesions in each body area (each on a 5 - point scale); 0 = none, 1 = slight, 2 = moderate, 3 = marked, and 4 = very marked. The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity. The PASI100 responses were based on 100% improvement in the PASI score at the Baseline of PS0016. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants With Investigator´s Global Assessment (IGA) Response (Clear or Almost Clear With at Least a 2 Category Improvement From Baseline on a 5-point Scale) During the Study | A static IGA for Psoriasis (PSO) was used to assess disease severity in all study participants during the study. IGA is a 5 point scale ranging from 0=Clear to 4=Severe. The response was defined as clear [0] or almost clear [1] with at least 2 category improvement from PS0016 Baseline. Clear was defined as no signs of PSO; post-inflammatory hyperpigmentation may be present. Almost clear was defined as no thickening; normal to pink coloration; no to minimal focal scaling. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Mean Change From PS0016 [NCT03025542] Baseline in PASI Score During the Study | The total PASI score ranges from 0 to 72 with a reduction from PS0016 Baseline indicating improvement. Missing data was imputed using Last observation carried forward (LOCF) at all visits. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Mean Percentage Change From PS0016 [NCT03025542] Baseline in PASI Score During the Study | A negative percentage change from PS0016 baseline indicated improvement in Total PASI score. The total PASI score ranges from 0 to 72 with a reduction from PS0016 Baseline indicating improvement. Missing data was imputed using Last Observation Carried Forward (LOCF) at all visits. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Who Shifted From Moderate Investigator´s Global Assessment (IGA) Score at PS0016 [NCT03025542] Baseline to Clear IGA Score During the Study | A static IGA for Psoriasis (PSO) was used to assess disease severity in all study participants during the study. IGA is a 5 point scale ranging from 0 = Clear to 4 = Severe. Moderate IGA was defined as clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling. Clear IGA was defined as no signs of PSO; post-inflammatory hyperpigmentation may be present. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Who Shifted From Moderate Investigator´s Global Assessment (IGA) Score at PS0016 [NCT03025542] Baseline to Almost Clear IGA Score During the Study | A static IGA for Psoriasis (PSO) was used to assess disease severity in all study participants during the study. IGA is a 5 point scale ranging from 0 = Clear to 4 = Severe. Moderate IGA was defined as clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling. Almost clear was defined as no thickening; normal to pink coloration; no to minimal focal scaling. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Who Shifted From Moderate Investigator´s Global Assessment (IGA) Score at PS0016 [NCT03025542] Baseline to Mild IGA Score During the Study | A static IGA for Psoriasis (PSO) was used to assess disease severity in all study participants during the study. IGA is a 5 point scale ranging from 0 = Clear to 4 = Severe. Moderate IGA was defined as clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling. Mild was defined as just detectable to mild thickening; pink to light red coloration; predominately fine scaling. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Who Shifted From Moderate Investigator´s Global Assessment (IGA) Score at PS0016 [NCT03025542] Baseline to Moderate IGA Score During the Study | A static IGA for Psoriasis (PSO) was used to assess disease severity in all study participants during the study. IGA is a 5 point scale ranging from 0 = Clear to 4 = Severe. Moderate IGA was defined as clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Who Shifted From Moderate Investigator´s Global Assessment (IGA) Score at PS0016 [NCT03025542] Baseline to Severe IGA Score During the Study | A static IGA for Psoriasis (PSO) was used to assess disease severity in all study participants during the study. IGA is a 5 point scale ranging from 0 = Clear to 4 = Severe. Moderate IGA was defined as clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling. Severe was defined as severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Who Shifted From Severe Investigator´s Global Assessment (IGA) Score at PS0016 [NCT03025542] Baseline to Clear IGA Score During the Study | A static IGA for Psoriasis (PSO) was used to assess disease severity in all study participants during the study. IGA is a 5 point scale ranging from 0 = Clear to 4 = Severe. Severe IGA was defined as severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. Clear was defined as no signs of PSO; post-inflammatory hyperpigmentation may be present. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Who Shifted From Severe Investigator´s Global Assessment (IGA) Score at PS0016 [NCT03025542] Baseline to Almost Clear IGA Score During the Study | A static IGA for Psoriasis (PSO) was used to assess disease severity in all study participants during the study. IGA is a 5 point scale ranging from 0 = Clear to 4 = Severe. Severe IGA was defined as severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. Almost clear was defined as no thickening; normal to pink coloration; no to minimal focal scaling. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Who Shifted From Severe Investigator´s Global Assessment (IGA) Score at PS0016 [NCT03025542] Baseline to Mild IGA Score During the Study | A static IGA for Psoriasis (PSO) was used to assess disease severity in all study participants during the study. IGA is a 5 point scale ranging from 0 = Clear to 4 = Severe. Severe IGA was defined as severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. Mild was defined as just detectable to mild thickening; pink to light red coloration; predominately fine scaling. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Who Shifted From Severe Investigator´s Global Assessment (IGA) Score at PS0016 [NCT03025542] Baseline to Moderate IGA Score During the Study | A static IGA for Psoriasis (PSO) was used to assess disease severity in all study participants during the study. IGA is a 5 point scale ranging from 0 = Clear to 4 = Severe. Severe IGA was defined as severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. Moderate was defined as clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Percentage of Participants Who Shifted From Severe Investigator´s Global Assessment (IGA) Score at PS0016 [NCT03025542] Baseline to Severe IGA Score During the Study | A static IGA for Psoriasis (PSO) was used to assess disease severity in all study participants during the study. IGA is a 5 point scale ranging from 0 = Clear to 4 = Severe. Severe IGA was defined as severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Mean Percentage in the Body Surface Area (BSA) Affected by Psoriasis During the Study | The BSA palm method was used for the evaluation of BSA as follows: Body surface area estimation used the palm (study participant's flat hand and thumb together, fingers included) as representing around 1% of the total BSA. Missing data was imputed using Last Observation Carried forward (LOCF) at all visits. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Mean Percentage Change From PS0016 [NCT03025542] Baseline in the Body Surface Area (BSA) Affected by Psoriasis During the Study | The percentage BSA (0 to 100%) affected by PSO was listed by PS0016 randomized treatment, by study participant and visit including the percentage change from PS0016 Baseline. The BSA palm method was used for the evaluation of BSA as follows: Body surface area estimation used the palm (study participant's flat hand and thumb together, fingers included) as representing around 1% of the total BSA. Missing data was imputed using Last observation carried forward (LOCF) at all visits. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | From Baseline of study PS0016 [NCT03025542] until Safety Follow Up Visit (up to Week 64) of study PS0018 | 
| Mean Change From PS0016 [NCT03025542] Baseline in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) Score During the Study | HADS-A score is the sum of the 7 individual scores in the anxiety domain and ranges from 0 to 21 with higher scores indicating worse state. A score below 8 was considered normal whereas a score of 15 and above was considered severe. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | Week 0, 12, 24, 36, and 48 of study PS0018, Relative to Baseline of study PS0016 [NCT03025542] | 
| Mean Change From PS0016 [NCT03025542] Baseline in Hospital Anxiety and Depression Scale - Depression (HADS-D) Score During the Study | HADS-D score is the sum of the 7 individual scores in the depression domain and ranges from 0 to 21 with higher scores indicating worse state. A score below 8 was considered normal whereas a score of 15 and above was considered severe. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | Week 0, 12, 24, 36, and 48 of study PS0018, Relative to Baseline of study PS0016 [NCT03025542] | 
| Percentage of Participants With Scores Below 8 in HADS-A (Participants With Normal Scores) During the Study | HADS-A score is the sum of the 7 individual scores in the anxiety domain and ranges from 0 to 21 with higher scores indicating worse state. A score below 8 was considered normal. Percentages were based on the number of participants with a non-missing measurement at the visit. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | Baseline of study PS0016 [NCT03025542], Week 0, 12, 24, 36, and 48 of study PS0018 | 
| Percentage of Participants With Scores Below 8 in HADS-D (Participants With Normal Scores) During the Study | HADS-D score is the sum of the 7 individual scores in the depression domain and ranges from 0 to 21 with higher scores indicating worse state. A score below 8 was considered normal. Percentages were based on the number of participants with a non-missing measurement at the visit. Baseline was defined as the last available value prior to the first injection of study medication in the PS0016 study. | Baseline of study PS0016 [NCT03025542], Week 0, 12, 24, 36, and 48 of study PS0018 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Psoriasis, Chronic Plaque Psoriasis, Bimekizumab