Chronic Plaque Psoriasis, Moderate to Severe Chronic Plaque Psoriasis
Conditions
Keywords
Bimekizumab, PSO, Psoriasis
Brief summary
This is a study to evaluate the long-term safety and tolerability of bimekizumab in adult subjects with moderate to severe chronic plaque psoriasis (PSO).
Detailed description
The study consists of a 144-week Treatment Period (open-label) and an optional 48-week Open-Label Extension Period 2 (OLE2) for eligible subjects in the USA and Canada.
Interventions
DRUGBimekizumab
Subjects will receive bimekizumab at pre-specified time-points.
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Treatment Period (open-label) * Subject is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, and medication intake according to the judgment of the Investigator * Subject completes the feeder study (PS0008 \[NCT03412747\], PS0009 \[NCT03370133\], PS0013 \[NCT03410992\]) without meeting any withdrawal criteria * Female subjects must be: 1. Postmenopausal: Menopause is defined as 12 consecutive months of amenorrhea, for which there is no other obvious pathological or physiological cause 2. Permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy) 3. Or, if of childbearing potential (and engaged in sexual activity that could result in procreation), must be willing to use a highly effective method of contraception throughout the duration of the study until 20 weeks after last administration of investigational medicinal product (IMP), and have a negative pregnancy test at the feeder study in final visit/Baseline visit in PS0014 OLE2 Period (USA and Canada) * Completed the OLE Period without meeting any withdrawal criteria * Compliant with ongoing clinical study requirements * Female subject of childbearing potential must be willing to use highly effective method of contraception * Subjects with a diagnosis of Crohn's disease or ulcerative colitis are allowed as long as they have no active symptomatic disease (US only) * Signed a separate OLE2 Period ICF
Exclusion criteria
Treatment Period (open-label) * Subject has previously participated in this study * Female subjects who plan to become pregnant during the study or within 20 weeks following last dose of study medication * 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 in the feeder study, the Medical Monitor must be consulted prior to the subject's entry into PS0014, although the decision on whether to enroll the subject remains with the Investigator * Subject has a positive or indeterminate interferon gamma release assay (IGRA) in a feeder study, unless appropriately evaluated and treated * Subject may not participate in another study of a medicinal product or device under investigation other than the substudy * Subject has a history of chronic alcohol or drug abuse within 6 months prior to Baseline as assessed by medical history, site interview, and/or results of the specified urine drug screen OLE2 Period (USA and Canada) * Subject has developed any medical or psychiatric condition, which, in the Investigator's judgment, would make the subject unsuitable for inclusion in OLE2 Period * Subject had a positive or indeterminate interferon-gamma release assay (IGRA) in the OLE study to Week 144, unless appropriately evaluated and treated * Presence of active suicidal ideation or severe depression * Subject has developed any active malignancy or history of malignancy prior to the OLE2 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 |
|---|---|---|
| Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Investigational Medicinal Product (IMP) | From Baseline up to 165 weeks for each study participant not entering the OLE2 Period and up to 212 weeks for participants entering OLE2 Period | The number of TEAEs adjusted by duration of exposure to study treatment were 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 first occurrence of the AE being considered. If a participant had no events, the total time at risk was used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to IMP | From Baseline up to 165 weeks for each study participant not entering the OLE2 Period and up to 212 weeks for participants entering OLE2 Period | The number of SAEs adjusted by duration of exposure to study treatment were 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 is used. |
| Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to IMP | From Baseline up to 165 weeks for each study participant not entering the OLE2 Period and up to 212 weeks for participants entering OLE2 Period | The number of TEAEs leading to withdrawal adjusted by duration of exposure to study treatment were scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used. |
| Psoriasis Area Severity Index 90 (PASI90) Response at Week 144 (Non-responder Imputation) | Week 144 compared to Baseline of Feeder study for Cohort A and Baseline of PS0014 for Cohort B | The PASI90 response assessments were based on improvement (reduction) of at least 90% in the PASI score compared to Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for redness, thickness, and scaling for each of the 4 body areas with score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI=average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. |
| Psoriasis Area Severity Index 90 (PASI90) Response at Week 144 (Observed Case) | Week 144 compared to Baseline of PS0014 for Cohort B | PASI90 response assessments were based on improvement (reduction) of at least 90% in the PASI score compared to Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for redness, thickness, and scaling for each of the 4 body areas with score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI=average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by involved psoriasis area score of respective section, and weighted by percentage of person's affected skin for respective section. Minimum score is 0= no disease, maximum score is 72= maximal disease. |
| Investigator´s Global Assessment (IGA) 0/1 Response at Week 144 (Non-responder Imputation) | Week 144 compared to Baseline of Feeder study for Cohort A and Baseline of PS0014 for Cohort B | The Investigator assessed the overall severity of psoriasis using the following 5-point scale: 0 = Clear (no signs of psoriasis; post-inflammatory hyperpigmentation may be present); 1= Almost clear (no thickening; normal to pink coloration; no to minimal focal scaling); 2= Mild (just detectable to mild thickening; pink to light red coloration; predominately fine scaling); 3= Moderate (clearly distinguishable to moderate thickening; dull to bright red coloration; moderate scaling); 4= Severe (Severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions). IGA response -IGA score of clear \[0\] or almost clear \[1\] with at least two category improvement from Baseline at visit timepoint. |
| Investigator´s Global Assessment (IGA) 0/1 Response at Week 144 (Observed Case) | Week 144 for Cohort B EP and GPP groups | The Investigator assessed the overall severity of psoriasis using the following 5-point scale: 0 = Clear (no signs of psoriasis; post-inflammatory hyperpigmentation may be present); 1= Almost clear (no thickening; normal to pink coloration; no to minimal focal scaling); 2= Mild (just detectable to mild thickening; pink to light red coloration; predominately fine scaling); 3= Moderate (clearly distinguishable to moderate thickening; dull to bright red coloration; moderate scaling); 4= Severe (Severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions). IGA response -IGA score of 0 or 1 at Week 144. |
Countries
Australia, Belgium, Canada, Germany, Hungary, Italy, Japan, Poland, Russia, South Korea, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORUCB Cares
001 844 599 2273
Participant flow
Recruitment details
The study started to enroll participants in September 2018 and concluded in November 2023. Participant flow refers to the Cohort A Safety Set, Cohort A OLE2 Period Set and Cohort B Safety Set. Participants who enrolled in PS0014 after completion of Phase 3 feeder studies were included in Cohort A. An additional Cohort B was added in Japan.
Pre-assignment details
Cohort A has Treatment Period (TP) (144 wks) followed by SFU Visit (20 wks after final dose). Cohort B has Screening Period (2 to 5 wks) and TP (144 wks) followed by SFU Visit (20 wks after final dose). After Protocol Amendment 3.3 (US) and 3.4 (Canada), 48-week OLE2 Period followed by SFU2 Visit (20 wks after final dose) was added in Cohort A.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: BKZ 320 mg Q8W Based on the PASI90 response and the treatment/dose the participant was receiving in the feeder studies (PS0008 \[NCT03412747\], PS0009 \[NCT03370133\], and PS0013 \[NCT03410992\]), participants were randomized to receive BKZ 320 milligrams (mg) subcutaneously (sc) every 8 weeks (Q8W) in this study during the 144-week (wk) Treatment Period. The BKZ 320 mg Q8W group consisted of all participants who received only Q8W during PS0014 study and did not switch dosing regimen at any time point. | 384 |
| Cohort A: BKZ 320 mg Q4W/Q8W Based on the PASI90 response and the treatment/dose the participant was receiving in the feeder study, participants were randomized to receive BKZ 320 mg sc every 4 weeks (Q4W) in this study during the 144-week Treatment Period. The participants switched to BKZ 320 mg Q8W as per protocol. The BKZ 320mg Q4W/Q8W group consisted of all participants who switched from Q4W to Q8W dosing at any of the scheduled switching time points during the study. | 833 |
| Cohort A: BKZ 320 mg Q4W Based on the PASI90 response and the treatment/dose the participant was receiving in the feeder study, participants were randomized to receive BKZ 320 mg sc Q4W in this study during the 144-week Treatment Period. The BKZ 320 mg Q4W group consisted of participants who discontinued prior to the planned change of dosing interval from BKZ 320 mg Q4W to BKZ 320 mg Q8W. | 70 |
| Cohort B: PSO BKZ Total Participants with chronic plaque psoriasis (PSO) in Cohort B received BKZ 320 mg sc Q4W until Week 16 and 320 mg Q8W thereafter through Week 40. At Week 48, Cohort B participants with chronic plaque PSO continued BKZ 320 mg Q8W up to Week 144. If the participant's dosing interval had changed to BKZ 320 mg Q4W under Protocol Amendment 1.2, the participant's dosing interval changed to BKZ 320 mg Q8W at the next scheduled clinic visit after implementation of Protocol Amendment 3.2. | 45 |
| Cohort B: EP BKZ Total Participants with erythrodermic psoriasis (EP) in Cohort B received BKZ 320 mg sc Q4W until Week 16. Based on IGA response, participants received either BKZ 320 mg sc Q4W or BKZ 320 mg sc Q8W up to Week 144. | 11 |
| Cohort B: GPP BKZ Total Participants with generalized pustular psoriasis (GPP) in Cohort B received BKZ 320 mg sc Q4W until Week 16. Based on IGA response, participants received either BKZ 320 mg sc Q4W or BKZ 320 mg sc Q8W up to Week 144. | 10 |
| Total | 1,353 |
Baseline characteristics
| Characteristic | Cohort A: BKZ 320 mg Q4W/Q8W | Cohort A: BKZ 320 mg Q4W | Cohort B: PSO BKZ Total | Cohort B: EP BKZ Total | Cohort B: GPP BKZ Total | Cohort A: BKZ 320 mg Q8W | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 13.2 | 45.4 years STANDARD_DEVIATION 13.4 | 48.8 years STANDARD_DEVIATION 11.5 | 55.3 years STANDARD_DEVIATION 11.9 | 46.0 years STANDARD_DEVIATION 12.5 | 45.3 years STANDARD_DEVIATION 13.7 | 45.6 years STANDARD_DEVIATION 13.3 |
| Age, Customized 18 - <65 years | 757 Participants | 68 Participants | 42 Participants | 10 Participants | 10 Participants | 349 Participants | 1236 Participants |
| Age, Customized 65 - <85 years | 76 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 35 Participants | 117 Participants |
| Age, Customized >= 85 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 107 Participants | 8 Participants | 45 Participants | 11 Participants | 10 Participants | 31 Participants | 212 Participants |
| Race/Ethnicity, Customized Black | 14 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 17 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 40 Participants | 11 Participants | 0 Participants | 0 Participants | 0 Participants | 20 Participants | 71 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 793 Participants | 59 Participants | 45 Participants | 11 Participants | 10 Participants | 364 Participants | 1282 Participants |
| Race/Ethnicity, Customized Other/mixed | 14 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 21 Participants |
| Race/Ethnicity, Customized White | 695 Participants | 58 Participants | 0 Participants | 0 Participants | 0 Participants | 344 Participants | 1097 Participants |
| Sex: Female, Male Female | 221 Participants | 24 Participants | 9 Participants | 0 Participants | 4 Participants | 118 Participants | 376 Participants |
| Sex: Female, Male Male | 612 Participants | 46 Participants | 36 Participants | 11 Participants | 6 Participants | 266 Participants | 977 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 1,217 | 6 / 903 | 0 / 226 | 0 / 51 | 0 / 41 | 0 / 45 | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 771 / 1,217 | 566 / 903 | 97 / 226 | 16 / 51 | 21 / 41 | 43 / 45 | 11 / 11 | 9 / 10 |
| serious Total, serious adverse events | 124 / 1,217 | 65 / 903 | 11 / 226 | 5 / 51 | 4 / 41 | 7 / 45 | 5 / 11 | 2 / 10 |
Outcome results
Primary
Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Investigational Medicinal Product (IMP)
The number of TEAEs adjusted by duration of exposure to study treatment were 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 first occurrence of the AE being considered. If a participant had no events, the total time at risk was used.
Time frame: From Baseline up to 165 weeks for each study participant not entering the OLE2 Period and up to 212 weeks for participants entering OLE2 Period
Population: CA-SS -All Cohort A participants who received at least 1 dose of the IMP in this study. Cohort A OLE2 Period Set (CA-OL2S)-All participants who received at least 1 dose of BKZ in the OLE2 Period. Cohort B PSO SS-All participants with a diagnosis of PSO disease at Baseline. Cohort B EP-SS-All participants with a diagnosis of EP disease at Baseline. Cohort B GPP-SS-All participants with a diagnosis of GPP disease at Baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: BKZ 320 mg Q8W | Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Investigational Medicinal Product (IMP) | 97.83 no. of new events per 100 subject-years |
| Cohort A: BKZ 320 mg Q4W | Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Investigational Medicinal Product (IMP) | 179.68 no. of new events per 100 subject-years |
| Cohort A: Group A BKZ 320 mg Q8W | Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Investigational Medicinal Product (IMP) | 79.02 no. of new events per 100 subject-years |
| Cohort A: Group B BKZ 320 mg Q8W | Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Investigational Medicinal Product (IMP) | 77.11 no. of new events per 100 subject-years |
| Cohort A: Group B BKZ 320 mg Q4W/Q8W | Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Investigational Medicinal Product (IMP) | 73.78 no. of new events per 100 subject-years |
| Cohort B: PSO BKZ Total | Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Investigational Medicinal Product (IMP) | 244.08 no. of new events per 100 subject-years |
| Cohort B: EP BKZ Total | Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Investigational Medicinal Product (IMP) | 328.25 no. of new events per 100 subject-years |
| Cohort B: GPP BKZ Total | Number of Treatment Emergent Adverse Events (TEAEs) Adjusted by Duration of Subject Exposure to Investigational Medicinal Product (IMP) | 188.71 no. of new events per 100 subject-years |
Secondary
Investigator´s Global Assessment (IGA) 0/1 Response at Week 144 (Non-responder Imputation)
The Investigator assessed the overall severity of psoriasis using the following 5-point scale: 0 = Clear (no signs of psoriasis; post-inflammatory hyperpigmentation may be present); 1= Almost clear (no thickening; normal to pink coloration; no to minimal focal scaling); 2= Mild (just detectable to mild thickening; pink to light red coloration; predominately fine scaling); 3= Moderate (clearly distinguishable to moderate thickening; dull to bright red coloration; moderate scaling); 4= Severe (Severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions). IGA response -IGA score of clear \[0\] or almost clear \[1\] with at least two category improvement from Baseline at visit timepoint.
Time frame: Week 144 compared to Baseline of Feeder study for Cohort A and Baseline of PS0014 for Cohort B
Population: Cohort A FAS included all Cohort A enrolled study participants who received at least 1 dose of IMP and had a valid efficacy measurement for PASI at Baseline of the feeder study and at Baseline of this study. Cohort B Psoriasis FAS included study participants with chronic plaque PSO at Baseline. Study participants who had missing data at the Week 144 were treated as though they did not respond to the treatment using NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: BKZ 320 mg Q8W | Investigator´s Global Assessment (IGA) 0/1 Response at Week 144 (Non-responder Imputation) | 76.8 percentage of participants |
| Cohort A: BKZ 320 mg Q4W | Investigator´s Global Assessment (IGA) 0/1 Response at Week 144 (Non-responder Imputation) | 79.0 percentage of participants |
| Cohort A: Group A BKZ 320 mg Q8W | Investigator´s Global Assessment (IGA) 0/1 Response at Week 144 (Non-responder Imputation) | 0 percentage of participants |
| Cohort A: Group B BKZ 320 mg Q8W | Investigator´s Global Assessment (IGA) 0/1 Response at Week 144 (Non-responder Imputation) | 60.0 percentage of participants |
Secondary
Investigator´s Global Assessment (IGA) 0/1 Response at Week 144 (Observed Case)
The Investigator assessed the overall severity of psoriasis using the following 5-point scale: 0 = Clear (no signs of psoriasis; post-inflammatory hyperpigmentation may be present); 1= Almost clear (no thickening; normal to pink coloration; no to minimal focal scaling); 2= Mild (just detectable to mild thickening; pink to light red coloration; predominately fine scaling); 3= Moderate (clearly distinguishable to moderate thickening; dull to bright red coloration; moderate scaling); 4= Severe (Severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions). IGA response -IGA score of 0 or 1 at Week 144.
Time frame: Week 144 for Cohort B EP and GPP groups
Population: Cohort B GPP FAS included study participants with GPP at Baseline. Cohort B EP FAS included study participants with EP at Baseline. Only study participants with available data who had not discontinued study treatment at Week 144 were considered for the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: BKZ 320 mg Q8W | Investigator´s Global Assessment (IGA) 0/1 Response at Week 144 (Observed Case) | 80.0 percentage of participants |
| Cohort A: BKZ 320 mg Q4W | Investigator´s Global Assessment (IGA) 0/1 Response at Week 144 (Observed Case) | 85.7 percentage of participants |
Secondary
Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to IMP
The number of SAEs adjusted by duration of exposure to study treatment were 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 is used.
Time frame: From Baseline up to 165 weeks for each study participant not entering the OLE2 Period and up to 212 weeks for participants entering OLE2 Period
Population: CA-SS -All Cohort A participants who received at least 1 dose of the IMP in this study. CA-OL2S-All participants who received at least 1 dose of BKZ in the OLE2 Period. Cohort B PSO SS-All participants with a diagnosis of PSO disease at Baseline. Cohort B EP-SS-All participants with a diagnosis of EP disease at Baseline. Cohort B GPP-SS-All participants with a diagnosis of GPP disease at Baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: BKZ 320 mg Q8W | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to IMP | 5.24 no. of new events per 100 subject-years |
| Cohort A: BKZ 320 mg Q4W | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to IMP | 6.72 no. of new events per 100 subject-years |
| Cohort A: Group A BKZ 320 mg Q8W | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to IMP | 4.44 no. of new events per 100 subject-years |
| Cohort A: Group B BKZ 320 mg Q8W | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to IMP | 9.05 no. of new events per 100 subject-years |
| Cohort A: Group B BKZ 320 mg Q4W/Q8W | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to IMP | 8.93 no. of new events per 100 subject-years |
| Cohort B: PSO BKZ Total | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to IMP | 5.86 no. of new events per 100 subject-years |
| Cohort B: EP BKZ Total | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to IMP | 19.51 no. of new events per 100 subject-years |
| Cohort B: GPP BKZ Total | Number of Serious Adverse Events (SAEs) Adjusted by Duration of Subject Exposure to IMP | 7.56 no. of new events per 100 subject-years |
Secondary
Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to IMP
The number of TEAEs leading to withdrawal adjusted by duration of exposure to study treatment were scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used.
Time frame: From Baseline up to 165 weeks for each study participant not entering the OLE2 Period and up to 212 weeks for participants entering OLE2 Period
Population: CA-SS -All Cohort A participants who received at least 1 dose of the IMP in this study. CA-OL2S-All participants who received at least 1 dose of BKZ in the OLE2 Period. Cohort B PSO SS-All participants with a diagnosis of PSO disease at Baseline. Cohort B EP-SS-All participants with a diagnosis of EP disease at Baseline. Cohort B GPP-SS-All participants with a diagnosis of GPP disease at Baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: BKZ 320 mg Q8W | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to IMP | 2.11 no. of new events per 100 subject-years |
| Cohort A: BKZ 320 mg Q4W | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to IMP | 2.59 no. of new events per 100 subject-years |
| Cohort A: Group A BKZ 320 mg Q8W | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to IMP | 0.79 no. of new events per 100 subject-years |
| Cohort A: Group B BKZ 320 mg Q8W | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to IMP | 1.77 no. of new events per 100 subject-years |
| Cohort A: Group B BKZ 320 mg Q4W/Q8W | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to IMP | 4.37 no. of new events per 100 subject-years |
| Cohort B: PSO BKZ Total | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to IMP | 2.42 no. of new events per 100 subject-years |
| Cohort B: EP BKZ Total | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to IMP | 3.27 no. of new events per 100 subject-years |
| Cohort B: GPP BKZ Total | Number of TEAEs Leading to Withdrawal Adjusted by Duration of Subject Exposure to IMP | 7.68 no. of new events per 100 subject-years |
Secondary
Psoriasis Area Severity Index 90 (PASI90) Response at Week 144 (Non-responder Imputation)
The PASI90 response assessments were based on improvement (reduction) of at least 90% in the PASI score compared to Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for redness, thickness, and scaling for each of the 4 body areas with score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI=average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
Time frame: Week 144 compared to Baseline of Feeder study for Cohort A and Baseline of PS0014 for Cohort B
Population: Cohort A FAS included all Cohort A enrolled study participants who received at least 1 dose of IMP and had a valid efficacy measurement for PASI at Baseline of the feeder study and at Baseline of this study. Cohort B Psoriasis FAS included study participants with chronic plaque PSO at Baseline. Study participants who had missing data at the Week 144 were treated as though they did not respond to the treatment using Non-responder imputation (NRI) method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: BKZ 320 mg Q8W | Psoriasis Area Severity Index 90 (PASI90) Response at Week 144 (Non-responder Imputation) | 77.6 percentage of participants |
| Cohort A: BKZ 320 mg Q4W | Psoriasis Area Severity Index 90 (PASI90) Response at Week 144 (Non-responder Imputation) | 80.2 percentage of participants |
| Cohort A: Group A BKZ 320 mg Q8W | Psoriasis Area Severity Index 90 (PASI90) Response at Week 144 (Non-responder Imputation) | 0 percentage of participants |
| Cohort A: Group B BKZ 320 mg Q8W | Psoriasis Area Severity Index 90 (PASI90) Response at Week 144 (Non-responder Imputation) | 73.3 percentage of participants |
Secondary
Psoriasis Area Severity Index 90 (PASI90) Response at Week 144 (Observed Case)
PASI90 response assessments were based on improvement (reduction) of at least 90% in the PASI score compared to Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for redness, thickness, and scaling for each of the 4 body areas with score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI=average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by involved psoriasis area score of respective section, and weighted by percentage of person's affected skin for respective section. Minimum score is 0= no disease, maximum score is 72= maximal disease.
Time frame: Week 144 compared to Baseline of PS0014 for Cohort B
Population: Cohort B GPP FAS included study participants with GPP at Baseline. Cohort B EP FAS included study participants with EP at Baseline. Only study participants with available data who had not discontinued study treatment at Week 144 were considered for the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: BKZ 320 mg Q8W | Psoriasis Area Severity Index 90 (PASI90) Response at Week 144 (Observed Case) | 90.0 percentage of participants |
| Cohort A: BKZ 320 mg Q4W | Psoriasis Area Severity Index 90 (PASI90) Response at Week 144 (Observed Case) | 85.7 percentage of participants |