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

UCB Biopharma S.P.R.L.250 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

250

Conditions

Chronic Plaque Psoriasis

Interventions

BimekizumabDRUG

Subjects will be randomized to receive a combination of injections of Bimekizumab.

PlaceboOTHER

Subjects randomized to the placebo group, will receive a combination of several injections of Placebo to maintain the blinding.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (41)

Outcomes

Primary Outcomes

Percentage of Participants Achieving a 90% or Higher Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score at 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.

Time frame: Week 12

Secondary Outcomes

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

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.

Time frame: 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 8

Data from ClinicalTrials.gov

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Ps0010 711

Fremont, California, United States

Ps0010 708

Los Angeles, California, United States

Ps0010 706

Washington D.C., District of Columbia, United States

Ps0010 704

West Des Moines, Iowa, United States

Ps0010 718

Rochester, New York, United States

Ps0010 738

Wilmington, North Carolina, United States

Ps0010 736

Cleveland, Ohio, United States

Ps0010 712

Portland, Oregon, United States

Ps0010 733

Dallas, Texas, United States

Ps0010 702

Houston, Texas, United States

...and 31 more locations

Percentage of Participants Achieving a 90% or Higher Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 8

Time frame: Week 8

Percentage of Participants Achieving a 75% or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at 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.

Time frame: Week 12

Percentage of Participants Achieving a 100% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score at 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.

Time frame: Week 12

Plasma Concentrations of Bimekizumab During the Study

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.

Time frame: Baseline (Week 0), Week 1, Week 2, Week 4, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)

Population PK (Apparent Total Clearance (CL/F)) of Bimekizumab

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.

Time frame: From Baseline (Week 0) until Safety Follow-Up Visit (20 weeks after the last dose; Up to Week 28)

Population PK (Apparent Volume of Distribution (V/F)) of Bimekizumab

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.

Time frame: From Baseline (Week 0) until Safety Follow-Up Visit (20 weeks after the last dose; Up to Week 28)

Concentration of Bimekizumab Leading to 50% of Maximum Effect (EC50)

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.

Time frame: From Baseline (Week 0) until Safety Follow-Up Visit (20 weeks after the last dose; Up to Week 28)

Percentage of Participants With a Positive Anti-bimekizumab Antibody (AbAb) Status Prior to Study Treatment

Antibody positive status prior study treatment was defined as having an antibody level greater than (\>) 28.5% at Baseline (Week 0).

Time frame: Baseline (Week 0)

Percentage of Participants With an Overall Positive Anti-bimekizumab Antibody (AbAb) Status Following Study Treatment

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.

Time frame: From Week 4 until the Safety Follow-Up visit (20 weeks after the last dose; Up to Week 28)

Percentage of Participants With at Least One Adverse Event (AE) During the Study

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.

Time frame: From Screening to End of Safety Follow-up (up to Week 32)

Percentage of Participants With at Least One Adverse Event (AE) During the Study by Severity

Time frame: From Screening to End of Safety Follow-up (up to Week 32)

Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Platelets)

Platelets was measured in number of platelets per liter (10\^9/L).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration, Hemoglobin)

Erythrocytes mean corpuscular hemoglobin (HGB) concentration and hemoglobin were measured in grams per liter (g/L).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Erythrocytes Mean Corpuscular Hemoglobin (HGB))

Erythrocytes mean corpuscular hemoglobin (HGB) was measured in picograms (pg).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Erythrocytes Mean Corpuscular Volume)

Erythrocytes mean corpuscular volume was measured in femtolitres (fL).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Erythrocytes)

Erythrocytes was measured in number of red blood cells per liter (10\^12/L).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Hematocrit)

Hematocrit was measured in volume percentage (%) of red blood cells in blood.

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils)

Basophils, eosinophils, leukocytes, lymphocytes, monocytes and neutrophils were measured in number of white blood cells per liter (10\^9/L).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Biochemistry Parameters (Calcium, Chloride, Potassium, Magnesium, Sodium, Urea Nitrogen, Cholesterol, Glucose)

Calcium, chloride, potassium, magnesium, sodium, urea nitrogen, cholesterol and glucose were measured in millimoles per liter (mmol/L).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Biochemistry Parameters (Lactate Dehydrogenase, Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase)

Lactate dehydrogenase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transferase were measured in units per liter (U/L).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Biochemistry Parameters (Creatinine, Bilirubin)

Creatinine and bilirubin were measured in micromols per liter (μmol/L).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Biochemistry Parameters (C Reactive Protein)

C Reactive Protein was measured in milligrams per liters (mg/L).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Urinalysis Parameters (pH)

Urine pH was measured on a pH scale.

Time frame: 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)

Percentage of Participants Who Shifted From Baseline Until Week 12 in Urinalysis Parameters (Leukocyte Esterase)

Percentages were based on the number of participants with non-missing urinalysis results at Baseline and at Week 12.

Time frame: From Baseline (Week 0) until Week 12

Percentage of Participants Who Shifted From Baseline Until Week 12 in Urinalysis Parameters (Nitrite)

Percentages were based on the number of participants with non-missing urinalysis results at Baseline and at Week 12.

Time frame: From Baseline (Week 0) until Week 12

Percentage of Participants Who Shifted From Baseline Until Week 12 in Urinalysis Parameters (Occult Blood)

Percentages were based on the number of participants with non-missing urinalysis results at Baseline and at Week 12.

Time frame: From Baseline (Week 0) until Week 12

Percentage of Participants Who Shifted From Baseline Until Week 12 in Urinalysis Parameters (Urine Glucose)

Percentages were based on the number of participants with non-missing urinalysis results at Baseline and at Week 12.

Time frame: From Baseline (Week 0) until Week 12

Percentage of Participants Who Shifted From Baseline Until Week 12 in Urinalysis Parameters (Albumin)

Percentages were based on the number of participants with non-missing urinalysis results at Baseline and at Week 12.

Time frame: From Baseline (Week 0) until Week 12

Change From Baseline Until Safety Follow-up Visit in Vital Signs (Blood Pressure)

Blood pressure was measured in millimeters of mercury (mmHg).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Vital Signs (Pulse Rate)

Pulse rate was measured in beats per minute (beats/min).

Time frame: 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)

Change From Baseline Until Safety Follow-up Visit in Vital Signs (Temperature)

Temperature was measured in degrees Celsius (°C).

Time frame: 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)

Percentage of Participants With Clinically Significant Physical Examination Abnormalities

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.

Time frame: At Screening, Week 12/Early Withdrawal Visit and the Safety Follow-Up Visit (20 weeks after the last dose)

Percentage of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings

Percentages were based on the number of participants with a non-missing measurement for that variable at the visit.

Time frame: Baseline (Week 0), Week 2, Week 4, Week 6, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)