A Study to Evaluate the Efficacy and Safety of Bimekizumab Compared to an Active Comparator in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis
- Conditions
- Chronic Plaque PsoriasisModerate to Severe Chronic Plaque Psoriasis
- Interventions
- Registration Number
- NCT03536884
- Lead Sponsor
- UCB Biopharma SRL
- Brief Summary
This is a study to compare the efficacy of bimekizumab versus secukinumab in subjects with moderate to severe chronic plaque psoriasis (PSO).
- Detailed Description
The study consists of a 48-week double-blind Treatment Period, an optional 96-week open-label extension (OLE) Period and an optional 48-week OLE2 Period for eligible subjects in the USA and Canada.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 743
Double-blind Treatment Period
- Male or female at least 18 years of age
- Subject must have had chronic plaque psoriasis (PSO) for at least 6 months prior to the Screening visit
- Subject must have 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 must be a candidate for systemic PSO therapy and/or phototherapy
- Subject must be considered, in the opinion of the Investigator, to be a suitable candidate for treatment with secukinumab per regional labeling and has no contraindications to receive secukinumab as per the local label
- Female subject of childbearing potential must be willing to use highly effective method of contraception
Open-label extension (OLE) Period
- Completed the double-blind Treatment Period without meeting any withdrawal criteria
- All Week 48 visit assessments completed
- Compliant with ongoing clinical study requirements
- Signed a separate OLE Period Informed Consent Form (ICF)
- Female subject of childbearing potential must be willing to use highly effective method of contraception
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
Double-blind Treatment Period
- Subject has an active infection (except common cold), a serious infection, or a history of opportunistic, recurrent or chronic infections
- Subject has concurrent acute or chronic viral hepatitis B or C or human immunodeficiency virus (HIV) infection
- Subject has known tuberculosis (TB) infection, is at high risk of acquiring TB infection, or has current or history of nontuberculous mycobacterium (NTMB) infection
- Subject has any other condition, including medical or psychiatric, which, in the Investigator's judgment, would make the subject unsuitable for inclusion in the study
- Presence of active suicidal ideation or severe 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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bimekizumab dosage regimen 1 Placebo Subjects randomized to this arm will receive bimekizumab dosage regimen 1 (BKZ 1). At Week 16 subjects will be re-randomized and continue to receive BKZ 1 or to switch to bimekizumab regimen 2 (BKZ 2). Placebo will be administered at pre-specified time-points to maintain the blinding over the double-blind Treatment Period. Subjects allowed to enroll in the open-label extension (OLE) Period will receive BKZ 1 or BKZ 2. Subjects will switch from BKZ 1 to BKZ 2 at Week 64 or at the next scheduled Visit. Eligible subjects who completed OLE, have entered Safety Follow Up (SFU) or completed SFU would start OLE2 on BKZ 1 before switching to BKZ 2 after 16 weeks or start OLE2 on BKZ 2. Bimekizumab dosage regimen 2 Bimekizumab Subjects randomized to this arm will receive bimekizumab dosage regimen 2 (BKZ 2) starting at Week 16 after initial treatment on bimekizumab regimen 1 (BKZ 1) for 16 weeks. Placebo will be administered at pre-specified time-points to maintain the blinding over the double-blind Treatment Period. Subjects allowed to enroll in the open-label extension (OLE) Period will receive BKZ 1 or BKZ 2. Subjects will switch from BKZ 1 to BKZ 2 at Week 64 or at the next scheduled Visit. Eligible subjects who completed OLE, have entered SFU or completed SFU would start OLE2 on BKZ 1 before switching to BKZ 2 after 16 weeks or start OLE2 on BKZ 2. Bimekizumab dosage regimen 2 Placebo Subjects randomized to this arm will receive bimekizumab dosage regimen 2 (BKZ 2) starting at Week 16 after initial treatment on bimekizumab regimen 1 (BKZ 1) for 16 weeks. Placebo will be administered at pre-specified time-points to maintain the blinding over the double-blind Treatment Period. Subjects allowed to enroll in the open-label extension (OLE) Period will receive BKZ 1 or BKZ 2. Subjects will switch from BKZ 1 to BKZ 2 at Week 64 or at the next scheduled Visit. Eligible subjects who completed OLE, have entered SFU or completed SFU would start OLE2 on BKZ 1 before switching to BKZ 2 after 16 weeks or start OLE2 on BKZ 2. Secukinumab Secukinumab Subjects will receive secukinumab. Subjects allowed to enroll in the open-label extension (OLE) Period will be re-randomized to receive bimekizumab dosage regimen 1 (BKZ 1) or bimekizumab dosage regimen 2 (BKZ 2). Eligible subjects who completed OLE, have entered SFU or completed SFU would start OLE2 on BKZ 1 before switching to BKZ 2 after 16 weeks or start OLE2 on BKZ 2. Secukinumab Bimekizumab Subjects will receive secukinumab. Subjects allowed to enroll in the open-label extension (OLE) Period will be re-randomized to receive bimekizumab dosage regimen 1 (BKZ 1) or bimekizumab dosage regimen 2 (BKZ 2). Eligible subjects who completed OLE, have entered SFU or completed SFU would start OLE2 on BKZ 1 before switching to BKZ 2 after 16 weeks or start OLE2 on BKZ 2. Bimekizumab dosage regimen 1 Bimekizumab Subjects randomized to this arm will receive bimekizumab dosage regimen 1 (BKZ 1). At Week 16 subjects will be re-randomized and continue to receive BKZ 1 or to switch to bimekizumab regimen 2 (BKZ 2). Placebo will be administered at pre-specified time-points to maintain the blinding over the double-blind Treatment Period. Subjects allowed to enroll in the open-label extension (OLE) Period will receive BKZ 1 or BKZ 2. Subjects will switch from BKZ 1 to BKZ 2 at Week 64 or at the next scheduled Visit. Eligible subjects who completed OLE, have entered Safety Follow Up (SFU) or completed SFU would start OLE2 on BKZ 1 before switching to BKZ 2 after 16 weeks or start OLE2 on BKZ 2.
- Primary Outcome Measures
Name Time Method Percentage of Participants With a Psoriasis Area and Severity Index 100 (PASI100) Response at Week 16 Week 16 The PASI100 response assessments are based on 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With a PASI75 Response at Week 4 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 score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of body areas and converting to 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 16 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 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.
Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to IMP From Baseline up to Week 225 From Baseline up to Week 225 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.
Percentage of Participants With a PASI100 Response at Week 48 Week 48 The PASI100 response assessments are based on 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 InvestigatorĀ“s Global Assessment (IGA) Response (0/1) at Week 16 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.
Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Investigational Medicinal Product (IMP) From Baseline up to Week 225 From Baseline up to Week 225 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 TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to IMP From Baseline up to Week 225 From Baseline up to Week 225 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.
Trial Locations
- Locations (77)
Ps0015 222
š©šŖTuebingen, Germany
Ps0015 355
šµš±Bialystok, Poland
Ps0015 763
š¹š·Gaziantep, Turkey
PS0015 7
š¦šŗHectorville, Australia
Ps0015 236
š©šŖNeu-ulm, Germany
Ps0015 671
šØš¦Hamilton, Canada
Ps0015 265
š³š±Amsterdam, Netherlands
Ps0015 263
š³š±Breda, Netherlands
Ps0015 979
šŗšøDallas, Texas, United States
Ps0015 238
š©šŖMainz, Germany
Ps0015 920
šŗšøPortland, Oregon, United States
Ps0015 237
š©šŖBerlin, Germany
Ps0015 369
šµš±Bialystok, Poland
Ps0015 929
šŗšøPortland, Oregon, United States
Ps0015 11
š¦šŗParkville, Australia
Ps0015 661
šØš¦Peterborough, Canada
Ps0015 215
š©šŖLĆ¼beck, Germany
Ps0015 223
š©šŖAugsburg, Germany
Ps0015 211
š©šŖHamburg, Germany
Ps0015 153
š«š·Toulouse, France
Ps0015 219
š©šŖMĆ¼nster, Germany
PS0015 3
š¦šŗCarlton, Australia
Ps0015 978
šŗšøPflugerville, Texas, United States
Ps0015 234
š©šŖMĆ¼nchen, Germany
Ps0015 213
š©šŖMahlow, Germany
Ps0015 678
šØš¦Richmond Hill, Canada
Ps0015 361
šµš±Bialystok, Poland
Ps0015 352
šµš±Gdansk, Poland
PS0015 6
š¦šŗKogarah, Australia
PS0015 9
š¦šŗWoolloongabba, Australia
Ps0015 657
šØš¦Waterloo, Canada
Ps0015 663
šØš¦Mississauga, Canada
Ps0015 677
šØš¦Toronto, Canada
Ps0015 204
š©šŖWitten, Germany
Ps0015 379
šµš±Krakow, Poland
Ps0015 975
šŗšøSanta Ana, California, United States
Ps0015 939
šŗšøDanbury, Connecticut, United States
Ps0015 977
šŗšøPembroke Pines, Florida, United States
Ps0015 970
šŗšøWest Palm Beach, Florida, United States
Ps0015 954
šŗšøSkokie, Illinois, United States
Ps0015 924
šŗšøHouston, Texas, United States
Ps0015 976
šŗšøTampa, Florida, United States
Ps0015 969
šŗšøHigh Point, North Carolina, United States
Ps0015 921
šŗšøOrmond Beach, Florida, United States
Ps0015 903
šŗšøOcala, Florida, United States
Ps0015 936
šŗšøTampa, Florida, United States
Ps0015 972
šŗšøWest Dundee, Illinois, United States
Ps0015 966
šŗšøSandy Springs, Georgia, United States
Ps0015 900
šŗšøWest Des Moines, Iowa, United States
Ps0015 953
šŗšøSaint Louis, Missouri, United States
Ps0015 915
šŗšøClayton, Missouri, United States
Ps0015 944
šŗšøNew Orleans, Louisiana, United States
Ps0015 971
šŗšøWilmington, North Carolina, United States
Ps0015 901
šŗšøPortsmouth, New Hampshire, United States
Ps0015 965
šŗšøKew Gardens, New York, United States
Ps0015 980
šŗšøBexley, Ohio, United States
Ps0015 50
š§šŖBruxelles, Belgium
Ps0015 673
šØš¦Halifax, Canada
Ps0015 52
š§šŖLiege, Belgium
Ps0015 376
šµš±Krakow, Poland
Ps0015 366
šµš±Katowice, Poland
Ps0015 372
šµš±Lodz, Poland
Ps0015 368
šµš±Wroclaw, Poland
Ps0015 375
šµš±Wroclaw, Poland
Ps0015 451
šŖšøMadrid, Spain
Ps0015 455
šŖšøAlicante, Spain
Ps0015 450
šŖšøBarcelona, Spain
Ps0015 456
šŖšøMadrid, Spain
Ps0015 454
šŖšøMadrid, Spain
Ps0015 457
šŖšøSant Joan DespĆ, Spain
Ps0015 762
š¹š·Istanbul, Turkey
Ps0015 760
š¹š·Kayseri, Turkey
Ps0015 555
š¬š§Salford, United Kingdom
Ps0015 559
š¬š§Newcastle Upon Tyne, United Kingdom
Ps0015 54
š§šŖBrussels, Belgium
Ps0015 378
šµš±Katowice, Poland
Ps0015 377
šµš±Ostrowiec Swietokrzyski, Poland