Study to Evaluate Safety and Efficacy of Different Doses of Bimekizumab in Patients With Chronic Plaque Psoriasis

Phase 2

Completed

Conditions: Chronic Plaque Psoriasis

Interventions: Drug: Bimekizumab
Other: Placebo

Registration Number: NCT02905006

Lead Sponsor: UCB Biopharma S.P.R.L.

Brief Summary: This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose ranging study to investigate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of Bimekizumab compared with placebo in adult subjects with moderate to severe chronic plaque psoriasis in order to guide the selection of doses and clinical indices in the Phase 3 development program.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 250

Inclusion Criteria

Subject has provided informed consent
Chronic plaque psoriasis for at least 6 months prior to Screening
PASI (Psoriasis Area and Severity Index) >=12 and BSA (body surface area) >=10% and IGA (Investigator's Global Assessment) score 3 or greater on a 5-point scale
Candidates for systemic psoriasis therapy and/or phototherapy and/or chemophototherapy
Female subjects must be postmenopausal, permanently sterilized or, if of childbearing potential, must be willing to use a highly effective method of contraception up till 20 weeks after last administration of study drug
Male subjects with a partner of childbearing potential must be willing to use a condom when sexually active, up till 20 weeks after the last administration of study medication

Exclusion Criteria

Subjects with erythrodermic, guttate, pustular form of psoriasis, or drug-induced psoriasis
Subject has any severe, progressive and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, gastrointestinal or neurological disease
Subject has any significant concurrent medical condition or laboratory abnormalities, as defined in the study protocol
Subject taking prohibited psoriatic medications
Subject receiving any live vaccines within 8 weeks prior to the Baseline and subjects receiving Bacillus Calmette-Guerin (BCG) vaccination within 1 year prior to study drug administration
Subject has previously received treatment with any anti-interleukin-17 (anti-IL-17) therapy or has been exposed to more than 1 biological response modifier (limited to anti-tumor necrosis factor (TNF) or IL-12/23) for psoriatic arthritis or psoriasis prior to the Baseline
Subject has any current sign or symptom that may indicate an active infection (except for common cold)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bimekizumab dosing regimen 4	Placebo	-
Placebo	Placebo	-
Bimekizumab dosing regimen 1	Bimekizumab	-
Bimekizumab dosing regimen 1	Placebo	-
Bimekizumab dosing regimen 2	Bimekizumab	-
Bimekizumab dosing regimen 2	Placebo	-
Bimekizumab dosing regimen 3	Bimekizumab	-
Bimekizumab dosing regimen 3	Placebo	-
Bimekizumab dosing regimen 5	Bimekizumab	-
Bimekizumab dosing regimen 4	Bimekizumab	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving a 90% or Higher Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 12	Week 12	The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. 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.

Secondary Outcome Measures

Name	Time	Method
Population PK (Apparent Volume of Distribution (V/F)) of Bimekizumab	From Baseline (Week 0) until Safety Follow-Up Visit (20 weeks after the last dose; Up to Week 28)	The data were presented as population estimates of V/F. Given the sparse nature of PK sampling, V/F cannot be estimated for each treatment group. It was prespecified in the data analysis plan to combine doses to perform Population PK and PK/PD analysis based on a prior determination that the PK parameters are not dose-dependent.
Percentage of Participants With an Overall Positive Anti-bimekizumab Antibody (AbAb) Status Following Study Treatment	From Week 4 until the Safety Follow-Up visit (20 weeks after the last dose; Up to Week 28)	Overall antibody positive was defined as having a value of \> 28.5% at any time in the Treatment Period. The Treatment Period did not include Baseline/pretreatment samples.
Percentage of Participants Achieving a 75% or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 12	Week 12	The PASI75 response assessments are based on at least 75% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. 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 Achieving a 100% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 12	Week 12	PASI correlates to the physician's assessment of psoriasis symptoms including redness of lesions, thickness of lesions, scaliness of lesions and extent of disease. Each parameter is graded from 0-4, 0 refers to no disease and 4 to severe involvement. The body is divided into 4 areas for scoring (head, arms, trunk to groin, legs to top of buttocks), and the final score ranges from 0-72. The PASI 100 response rate at Week 12 is measured as the percentage of participants who achieved 100% improvement from baseline PASI at Week 12.
Percentage of Participants With Investigator's Global Assessment (IGA) (Clear or Almost Clear With at Least 2 Category Improvement From Baseline) Response at Week 12	Week 12	The Investigator's Global Assessment (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.
Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Hematocrit)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Hematocrit was measured in volume percentage (%) of red blood cells in blood.
Percentage of Participants With Investigator's Global Assessment (IGA) (Clear or Almost Clear With at Least 2 Category Improvement From Baseline) Response at Week 8	Week 8	The Investigator's Global Assessment (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.
Percentage of Participants Achieving a 90% or Higher Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 8	Week 8	The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. 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.
Plasma Concentrations of Bimekizumab During the Study	Baseline (Week 0), Week 1, Week 2, Week 4, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Bimekizumab plasma concentration was expressed in micrograms per milliliter (μg/mL). Values Below Limit of Quantification (BLQ) were replaced by the value of lower limit of quantification (LLOQ) divided by 2 = 0.075 μg/mL in the calculations of geometric mean and confidence intervals (CIs). Geometric mean was only calculated if at least two-thirds of the concentrations were quantified at the respective time point.
Concentration of Bimekizumab Leading to 50% of Maximum Effect (EC50)	From Baseline (Week 0) until Safety Follow-Up Visit (20 weeks after the last dose; Up to Week 28)	The data were presented as population estimates of EC50. EC50 was estimated based on all available data and cannot be derived for each treatment arm. It was prespecified in the data analysis plan to combine doses to perform Population PK and PK/PD analysis based on a prior determination that the PK parameters are not dose-dependent.
Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Erythrocytes)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Erythrocytes was measured in number of red blood cells per liter (10\^12/L).
Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Basophils, eosinophils, leukocytes, lymphocytes, monocytes and neutrophils were measured in number of white blood cells per liter (10\^9/L).
Change From Baseline Until Safety Follow-up Visit in Biochemistry Parameters (Creatinine, Bilirubin)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Creatinine and bilirubin were measured in micromols per liter (μmol/L).
Change From Baseline Until Safety Follow-up Visit in Biochemistry Parameters (C Reactive Protein)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	C Reactive Protein was measured in milligrams per liters (mg/L).
Percentage of Participants Who Shifted From Baseline Until Week 12 in Urinalysis Parameters (Leukocyte Esterase)	From Baseline (Week 0) until Week 12	Percentages were based on the number of participants with non-missing urinalysis results at Baseline and at Week 12.
Percentage of Participants Who Shifted From Baseline Until Week 12 in Urinalysis Parameters (Urine Glucose)	From Baseline (Week 0) until Week 12	Percentages were based on the number of participants with non-missing urinalysis results at Baseline and at Week 12.
Percentage of Participants Who Shifted From Baseline Until Week 12 in Urinalysis Parameters (Albumin)	From Baseline (Week 0) until Week 12	Percentages were based on the number of participants with non-missing urinalysis results at Baseline and at Week 12.
Change From Baseline Until Safety Follow-up Visit in Vital Signs (Blood Pressure)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Blood pressure was measured in millimeters of mercury (mmHg).
Percentage of Participants With Clinically Significant Physical Examination Abnormalities	At Screening, Week 12/Early Withdrawal Visit and the Safety Follow-Up Visit (20 weeks after the last dose)	The physical examination included general appearance; ear, nose, and throat; eyes, hair, and skin; respiratory; CV; GI; musculoskeletal; hepatic; neurological (including limb reflexes); and mental status. Any clinically significant abnormal findings during the study were captured as adverse events.
Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Platelets)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Platelets was measured in number of platelets per liter (10\^9/L).
Percentage of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings	Baseline (Week 0), Week 2, Week 4, Week 6, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Percentages were based on the number of participants with a non-missing measurement for that variable at the visit.
Population PK (Apparent Total Clearance (CL/F)) of Bimekizumab	From Baseline (Week 0) until Safety Follow-Up Visit (20 weeks after the last dose; Up to Week 28)	The data were presented as population estimates of CL/F. Given the sparse nature of PK sampling, CL/F cannot be estimated for each treatment group. It was prespecified in the data analysis plan to combine doses to perform Population PK and PK/PD analysis based on a prior determination that the PK parameters are not dose-dependent.
Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Erythrocytes Mean Corpuscular Volume)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Erythrocytes mean corpuscular volume was measured in femtolitres (fL).
Change From Baseline Until Safety Follow-up Visit in Biochemistry Parameters (Calcium, Chloride, Potassium, Magnesium, Sodium, Urea Nitrogen, Cholesterol, Glucose)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Calcium, chloride, potassium, magnesium, sodium, urea nitrogen, cholesterol and glucose were measured in millimoles per liter (mmol/L).
Change From Baseline Until Safety Follow-up Visit in Urinalysis Parameters (pH)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Urine pH was measured on a pH scale.
Percentage of Participants With a Positive Anti-bimekizumab Antibody (AbAb) Status Prior to Study Treatment	Baseline (Week 0)	Antibody positive status prior study treatment was defined as having an antibody level greater than (\>) 28.5% at Baseline (Week 0).
Percentage of Participants With at Least One Adverse Event (AE) During the Study	From Screening to End of Safety Follow-up (up to Week 32)	An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP.
Percentage of Participants With at Least One Adverse Event (AE) During the Study by Severity	From Screening to End of Safety Follow-up (up to Week 32)	An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP.
Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration, Hemoglobin)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Erythrocytes mean corpuscular hemoglobin (HGB) concentration and hemoglobin were measured in grams per liter (g/L).
Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Erythrocytes Mean Corpuscular Hemoglobin (HGB))	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Erythrocytes mean corpuscular hemoglobin (HGB) was measured in picograms (pg).
Change From Baseline Until Safety Follow-up Visit in Biochemistry Parameters (Lactate Dehydrogenase, Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Lactate dehydrogenase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transferase were measured in units per liter (U/L).
Percentage of Participants Who Shifted From Baseline Until Week 12 in Urinalysis Parameters (Nitrite)	From Baseline (Week 0) until Week 12	Percentages were based on the number of participants with non-missing urinalysis results at Baseline and at Week 12.
Percentage of Participants Who Shifted From Baseline Until Week 12 in Urinalysis Parameters (Occult Blood)	From Baseline (Week 0) until Week 12	Percentages were based on the number of participants with non-missing urinalysis results at Baseline and at Week 12.
Change From Baseline Until Safety Follow-up Visit in Vital Signs (Pulse Rate)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Pulse rate was measured in beats per minute (beats/min).
Change From Baseline Until Safety Follow-up Visit in Vital Signs (Temperature)	Baseline (Week 0), Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)	Temperature was measured in degrees Celsius (°C).

Trial Locations

Locations (40): Ps0010 736
🇺🇸
Cleveland, Ohio, United States
Ps0010 733
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Dallas, Texas, United States
Ps0010 709
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Houston, Texas, United States
Ps0010 738
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Wilmington, North Carolina, United States
Ps0010 708
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Los Angeles, California, United States
Ps0010 704
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West Des Moines, Iowa, United States
Ps0010 718
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Rochester, New York, United States
Ps0010 400
🇭🇺
Oroshaza, Hungary
Ps0010 300
🇨🇿
Ostrava Poruba, Czechia
Ps0010 301
🇨🇿
Praha, Czechia
Ps0010 503
🇯🇵
Tokio, Japan
Ps0010 603
🇵🇱
Podlaski, Poland
Ps0010 404
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Kecskemet, Hungary
Ps0010 610
🇵🇱
Gdynia, Poland
Ps0010 601
🇵🇱
Wroclaw, Poland
Ps0010 711
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Fremont, California, United States
Ps0010 706
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Washington, District of Columbia, United States
Ps0010 712
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Portland, Oregon, United States
Ps0010 702
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Houston, Texas, United States
Ps0010 203
🇨🇦
Surrey, British Columbia, Canada
Ps0010 204
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Hamilton, Ontario, Canada
Ps0010 214
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Quebec City, Canada
Ps0010 206
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Peterborough, Ontario, Canada
Ps0010 201
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North Bay, Ontario, Canada
Ps0010 205
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Waterloo, Ontario, Canada
Ps0010 209
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Edmonton, Canada
Ps0010 303
🇨🇿
Pardubice, Czechia
Ps0010 304
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Praha, Czechia
Ps0010 405
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Szekszard, Hungary
Ps0010 502
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Nagoya, Japan
Ps0010 501
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Shinaga Wa-ku, Japan
Ps0010 504
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Tokyo, Japan
Ps0010 600
🇵🇱
Bialystok, Poland
Ps0010 605
🇵🇱
Gdansk, Poland
Ps0010 608
🇵🇱
Krakow, Poland
Ps0010 604
🇵🇱
Kielce, Poland
Ps0010 606
🇵🇱
Lublin, Poland
Ps0010 607
🇵🇱
Warszawa, Poland
Ps0010 609
🇵🇱
Wroclaw, Poland
Ps0010 611
🇵🇱
Bialystok, Poland