A Study to Evaluate the Efficacy and Safety of Bimekizumab in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis (BE SURE)

• ClinicalTrials.gov Identifier: NCT03412747
• Recruitment Status: Completed
• First Posted: January 26, 2018
• Results First Posted: March 2, 2022
• Last Update Posted: February 23, 2023
• Sponsor: UCB Biopharma SRL
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma SRL )

Tracking Information

• First Submitted Date: January 22, 2018
• First Posted Date: January 26, 2018
• Results First Submitted Date: February 4, 2022
• Results First Posted Date: March 2, 2022
• Last Update Posted Date: February 23, 2023
• Actual Study Start Date: January 26, 2018
• Actual Primary Completion Date: February 7, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 4, 2022)

• Percentage of Participants With a Psoriasis Area and Severity Index 90 (PASI90) Response at Week 16 [ Time Frame: Week 16 ]
  The PASI90 response assessments are based on at least 90% improvement in PASI score from 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 a 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 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.
• Percentage of Participants With an Investigator's Global Assessment (IGA) Response (Clear or Almost Clear With at Least 2-Category Improvement Relative to Baseline) at Week 16 [ Time Frame: Week 16 ]
  The 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 [0] or almost clear [1] with at least a two-category improvement from Baseline at Week 16.

Original Primary Outcome Measures (submitted: January 25, 2018)

• Psoriasis Area and Severity Index 90 (PASI90) response at Week 16 [ Time Frame: Week 16 ]
  A PASI90 responder is defined as a subject that achieves 90% reduction from Baseline in the PASI score.
• Investigator's Global Assessment (IGA) response at Week 16 [ Time Frame: Week 16 ]
  IGA response is defined as Clear or Almost Clear with at least a 2-category improvement relative to Baseline.

Current Secondary Outcome Measures (submitted: February 4, 2022)

• Percentage of Participants With a PASI90 Response at Week 24 [ Time Frame: Week 24 ]
  The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and 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) 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 the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
• Percentage of Participants With an IGA Response (Clear or Almost Clear With at Least 2-category Improvement Relative to Baseline) at Week 24 [ Time Frame: Week 24 ]
  The 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 [0] with at least a two-category improvement from Baseline at Week 24.
• Percentage of Participants With a PASI75 Response at Week 4 [ Time Frame: Week 4 ]
  The PASI75 response assessments are based on at least 75% improvement in PASI score from 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 a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of 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 the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
• Percentage of Participants With a PASI100 Response at Week 16 [ Time Frame: Week 16 ]
  The PASI100 response assessments are based on a 100% improvement in PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and 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) to 4 (very marked). Determining the percentage of skin covered with PSO for each of 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 the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
• Percentage of Participants With a PASI100 Response at Week 24 [ Time Frame: Week 24 ]
  The PASI100 response assessments are based on a 100% improvement in the PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and 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) 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 the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
• Percentage of Participants With a PASI90 Response at Week 56 [ Time Frame: Week 56 ]
  PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. Body divided into 4 areas: head/arms/trunk to groin/and legs to top of buttocks. Assignment of an average score for the redness/thickness/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/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, max score is 72=maximal disease.
• Percentage of Participants With an IGA Response (Clear or Almost Clear With at Least 2-category Improvement Relative to Baseline) at Week 56 [ Time Frame: Week 56 ]
  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 [0]/almost clear [1] with at least a 2-category improvement from Baseline at Wk56.
• Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment From Baseline to Week 24 [ Time Frame: From Baseline to Week 24 ]
  The number of TEAEs adjusted by duration of exposure to study treatment was scaled such that 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.
• Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment From Baseline to Week 24 [ Time Frame: From Baseline to Week 24 ]
  The number of SAEs adjusted by duration of exposure to study treatment was 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.
• Number of Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment From Baseline to Week 24 [ Time Frame: From Baseline to Week 24 ]
  The number of TEAEs leading to discontinuation adjusted by duration of exposure to study treatment was 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.
• Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment From Baseline to Safety Follow-Up Visit (up to Week 72) [ Time Frame: From Baseline to Safety Follow-Up Visit (up to Week 72) ]
  The number of TEAEs adjusted by duration of exposure to study treatment was 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.
• Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment From Baseline to Safety Follow-Up Visit (up to Week 72) [ Time Frame: From Baseline to Safety Follow-Up Visit (up to Week 72) ]
  The number of SAEs adjusted by duration of exposure to study treatment was 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.
• Number of Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment From Baseline to Safety Follow-Up Visit (up to Week 72) [ Time Frame: From Baseline to Safety Follow-Up Visit (up to Week 72) ]
  The number of TEAEs leading to discontinuation adjusted by duration of exposure to study treatment was 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.

Original Secondary Outcome Measures (submitted: January 25, 2018)

• PASI90 response at Week 24 [ Time Frame: Week 24 ]
  A PASI90 responder is defined as a subject that achieves 90% reduction from Baseline in the PASI score.
• IGA response at Week 24 [ Time Frame: Week 24 ]
  IGA response is defined as Clear or Almost Clear with at least 2-category improvement relative to Baseline.
• PASI75 response at Week 4 [ Time Frame: Week 4 ]
  A PASI75 responder is defined as a subject that achieves 75% reduction from Baseline in the PASI score.
• PASI100 response at Week 16 [ Time Frame: Week 16 ]
  A PASI100 responder is defined as a subject that achieves 100% reduction from Baseline in the PASI score.
• PASI100 response at Week 24 [ Time Frame: Week 24 ]
  A PASI100 responder is defined as a subject that achieves 100% reduction from Baseline in the PASI score.
• PASI90 response at Week 56 [ Time Frame: Week 56 ]
  A PASI90 responder is defined as a subject that achieves 90% reduction from Baseline in the PASI score.
• IGA response at Week 56 [ Time Frame: Week 56 ]
  IGA response is defined as Clear or Almost Clear with at least 2-category improvement relative to Baseline.
• Number of Treatment Emergent Adverse Events (TEAEs) adjusted by duration of subject exposure to study treatment [ Time Frame: From Screening to Safety Follow Up (up to Week 76) ]
  The number of TEAEs adjusted by duration of exposure to study treatment is scaled such that it provides an incidence rate per 100 patient-years. If a subject has multiple events, the time of exposure is calculated to the first occurrence of the Adverse Event (AE) being considered. If a subject has no events, the total time at risk is used.
• Number of Serious Adverse Events (SAEs) adjusted by duration of subject exposure to study treatment [ Time Frame: From Screening to Safety Follow Up (up to Week 76) ]
  The number of adjusted SAEs by duration of exposure to study treatment is scaled such that it provides an incidence rate per 100 patient-years. If a subject has multiple events, the time of exposure is calculated to the first occurrence of the AE being considered. If a subject has no events, the total time at risk is used.
• Number of Treatment Emergent Adverse Events (TEAEs) leading to withdrawal adjusted by duration of subject exposure to study treatment [ Time Frame: From Screening to Safety Follow Up (up to Week 76) ]
  The number of TEAEs leading to discontinuation adjusted by duration of exposure to study treatment is scaled such that it provides an incidence rate per 100 patient-years. If a subject has multiple events, the time of exposure is calculated to the first occurrence of the AE being considered. If a subject has no events, the total time at risk is used.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy and Safety of Bimekizumab in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis
• Official Title: A Phase 3, Multicenter, Randomized, Double-Blind Study With an Active-Controlled Initial Treatment Period Followed by a Dose-Blind Maintenance Treatment Period to Evaluate the Efficacy and Safety of Bimekizumab in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis
• Brief Summary: This is a study to compare the efficacy of bimekizumab versus adalimumab in the treatment of subjects with moderate to severe chronic plaque psoriasis (PSO).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Chronic Plaque Psoriasis
• Moderate to Severe Plaque Psoriasis

Intervention

• Drug: Bimekizumab
  Subjects will receive bimekizumab at pre-defined timepoints in dose regimen 1 and/or dose regimen 2.
  Other Name: UCB4940
• Drug: Adalimumab
  Adalimumab will be administered according to the labeling recommendations.
  Other Name: Humira®
• Other: Placebo
  Subjects will receive Placebo at pre-specified time points to maintain the blinding of the Investigational Medicinal Products (IMP).
  Other Name: PBO

Study Arms

• Experimental: Bimekizumab Arm 1
  Subjects will receive bimekizumab dose regimen 1 for 56 weeks. Subjects will receive placebo at pre-specified time-points to maintain the blinding.
  Interventions:

  • Drug: Bimekizumab
  • Other: Placebo
• Experimental: Bimekizumab Arm 2
  Subjects will receive bimekizumab dose regimen 1 for 16 weeks and will proceed with bimekizumab dose regimen 2 until week 56. Subjects will receive placebo at pre-specified time-points to maintain the blinding.
  Interventions:

  • Drug: Bimekizumab
  • Other: Placebo
• Active Comparator: Adalimumab Arm
  Subjects will receive adalimumab for 24 weeks and will then receive bimekizumab dose regimen 1 until week 56. Subjects will receive placebo at pre-specified time-points to maintain the blinding.
  Interventions:

  • Drug: Bimekizumab
  • Drug: Adalimumab
  • Other: Placebo

Publications *

• Gordon KB, Langley RG, Warren RB, Okubo Y, Stein Gold L, Merola JF, Peterson L, Wixted K, Cross N, Deherder D, Thaci D. Bimekizumab Safety in Patients With Moderate to Severe Plaque Psoriasis: Pooled Results From Phase 2 and Phase 3 Randomized Clinical Trials. JAMA Dermatol. 2022 Jul 1;158(7):735-744. doi: 10.1001/jamadermatol.2022.1185.
• Thaci D, Vender R, de Rie MA, Conrad C, Pariser DM, Strober B, Vanvoorden V, Wang M, Madden C, de Cuyper D, Kimball AB. Safety and efficacy of bimekizumab through 2 years in patients with moderate-to-severe plaque psoriasis: longer-term results from the BE SURE randomized controlled trial and the open-label extension from the BE BRIGHT trial. Br J Dermatol. 2023 Jan 23;188(1):22-31. doi: 10.1093/bjd/ljac021.
• Warren RB, Blauvelt A, Bagel J, Papp KA, Yamauchi P, Armstrong A, Langley RG, Vanvoorden V, De Cuyper D, Cioffi C, Peterson L, Cross N, Reich K. Bimekizumab versus Adalimumab in Plaque Psoriasis. N Engl J Med. 2021 Jul 8;385(2):130-141. doi: 10.1056/NEJMoa2102388. Epub 2021 Apr 23.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 9, 2020): 478
• Original Estimated Enrollment (submitted: January 25, 2018): 450
• Actual Study Completion Date: February 26, 2020
• Actual Primary Completion Date: February 7, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Must be at least 18 years of age
• Chronic plaque 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 a known hypersensitivity to any excipients of bimekizumab or adalimumab
• Subject has an active infection (except common cold), a serious infection, or a history of opportunistic or recurrent 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
• Subject has had previous exposure to adalimumab
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Germany, Hungary, Korea, Republic of, Poland, Russian Federation, Taiwan, United States

Administrative Information

• NCT Number: NCT03412747
• Other Study ID Numbers: PS0008; 2016-003392-22 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• URL: http://www.Vivli.org

• Current Responsible Party: UCB Pharma ( UCB Biopharma SRL )
• Original Responsible Party: UCB Biopharma S.P.R.L.
• Current Study Sponsor: UCB Biopharma SRL
• Original Study Sponsor: UCB Biopharma S.P.R.L.
• Collaborators: Not Provided

Investigators

• Study Director: UCB Cares; +1 844 599 2273 (UCB)

• PRS Account: UCB Pharma
• Verification Date: July 2022