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 )

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Chronic Plaque Psoriasis; Moderate to Severe Plaque Psoriasis	Drug: Bimekizumab; Drug: Adalimumab; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 478 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 26, 2018
• Actual Primary Completion Date: February 7, 2019
• Actual Study Completion Date: February 26, 2020

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Bimekizumab; Subjects will receive bimekizumab at pre-defined timepoints in dose regimen 1 and/or dose regimen 2.; Other Name: UCB4940; Other: Placebo; Subjects will receive Placebo at pre-specified time points to maintain the blinding of the Investigational Medicinal Products (IMP).; Other Name: PBO
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.	Drug: Bimekizumab; Subjects will receive bimekizumab at pre-defined timepoints in dose regimen 1 and/or dose regimen 2.; Other Name: UCB4940; Other: Placebo; Subjects will receive Placebo at pre-specified time points to maintain the blinding of the Investigational Medicinal Products (IMP).; Other Name: PBO
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.	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

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Ps0008 957

Glendale, Arizona, United States, 85308

United States, California

Ps0008 927

Los Angeles, California, United States, 90033

Ps0008 955

San Diego, California, United States, 92123

Ps0008 943

San Luis Obispo, California, United States, 93405

Ps0008 967

Santa Monica, California, United States, 90404

United States, Connecticut

Ps0008 939

Danbury, Connecticut, United States, 06810

United States, District of Columbia

Ps0008 934

Washington, District of Columbia, United States, 20037

United States, Florida

Ps0008 906

Boca Raton, Florida, United States, 33486

Ps0008 936

Tampa, Florida, United States, 33624

United States, Iowa

Ps0008 900

West Des Moines, Iowa, United States, 50265

United States, Kansas

Ps0008 905

Overland Park, Kansas, United States, 66215

United States, Massachusetts

Ps0008 940

Beverly, Massachusetts, United States, 01844

Ps0008 925

Brighton, Massachusetts, United States, 02135

United States, Michigan

Ps0008 917

Troy, Michigan, United States, 48084

United States, New Jersey

Ps0008 908

East Windsor, New Jersey, United States, 08520

United States, North Carolina

Ps0008 961

Rocky Mount, North Carolina, United States, 27804

Ps0008 935

Winston-Salem, North Carolina, United States, 27104-35 20

United States, Oklahoma

Ps0008 932

Oklahoma City, Oklahoma, United States, 73112

United States, Oregon

Ps0008 929

Portland, Oregon, United States, 97223

United States, South Carolina

Ps0008 945

Greer, South Carolina, United States, 29650

United States, Texas

Ps0008 931

Dallas, Texas, United States, 75231

Ps0008 924

Houston, Texas, United States, 77004

Ps0008 951

Houston, Texas, United States, 77004

Australia

Ps0008 008

East Melbourne, Australia

Ps0008 004

Fremantle, Australia

Ps0008 007

Hectorville, Australia

Ps0008 010

Kogarah, Australia

Ps0008 005

Phillip, Australia

Ps0008 009

Woolloongabba, Australia

Canada

Ps0008 659

Calgary, Canada

Ps0008 663

Mississauga, Canada

Ps0008 660

Montréal, Canada

Ps0008 661

Peterborough, Canada

Ps0008 662

Toronto, Canada

Ps0008 664

Toronto, Canada

Ps0008 657

Waterloo, Canada

Ps0008 669

Windsor, Canada

Ps0008 670

Windsor, Canada

Ps0008 674

Winnipeg, Canada

Germany

Ps0008 207

Berlin, Germany

Ps0008 218

Bonn, Germany

Ps0008 203

Dresden, Germany

Ps0008 211

Hamburg, Germany

Ps0008 220

Hamburg, Germany

Ps0008 215

Lubeck, Germany

Ps0008 213

Mahlow, Germany

Ps0008 205

Osnabrück, Germany

Ps0008 217

Schweinfurt, Germany

Hungary

Ps0008 252

Budapest, Hungary

Ps0008 254

Budapest, Hungary

Ps0008 255

Budapest, Hungary

Ps0008 256

Debrecen, Hungary

Ps0008 251

Gyula, Hungary

Ps0008 260

Szeged, Hungary

Korea, Republic of

Ps0008 702

Gwangju, Korea, Republic of

Ps0008 700

Seoul, Korea, Republic of

Poland

Ps0008 355

Białystok, Poland

Ps0008 362

Białystok, Poland

Ps0008 371

Bydgoszcz, Poland

Ps0008 352

Gdańsk, Poland

Ps0008 359

Katowice, Poland

Ps0008 366

Katowice, Poland

Ps0008 363

Kraków, Poland

Ps0008 356

Lublin, Poland

Ps0008 364

Nowa Sól, Poland

Ps0008 353

Szczecin, Poland

Ps0008 354

Warszawa, Poland

Ps0008 365

Wrocław, Poland

Ps0008 367

Wrocław, Poland

Ps0008 373

Wrocław, Poland

Ps0008 360

Łódź, Poland

Ps0008 372

Łódź, Poland

Russian Federation

Ps0008 405

Saint Petersburg, Russian Federation

Ps0008 401

Saratov, Russian Federation

Ps0008 406

Yaroslavl, Russian Federation

Taiwan

Ps0008 754

Taipei, Taiwan

Ps0008 755

Taipei, Taiwan

Sponsors and Collaborators

UCB Biopharma SRL

Investigators

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

  Study Documents (Full-Text)

Documents provided by UCB Pharma ( UCB Biopharma SRL ):

Study Protocol  [PDF] April 6, 2018

Statistical Analysis Plan  [PDF] October 31, 2019

More Information

Additional Information:

Product Information 

FDA Safety Alerts and Recalls 

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: UCB Biopharma SRL
• ClinicalTrials.gov Identifier: NCT03412747
• Other Study ID Numbers: PS0008; 2016-003392-22 ( EudraCT Number )
• First Posted: January 26, 2018
• Results First Posted: March 2, 2022
• Last Update Posted: February 23, 2023
• Last Verified: July 2022

Individual Participant Data (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; Statistical Analysis Plan (SAP); 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

• 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

Keywords provided by UCB Pharma ( UCB Biopharma SRL ):

Bimekizumab; PSO; Psoriasis

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Adalimumab; Tumor Necrosis Factor Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents