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

Chronic Plaque Psoriasis Clinical Trial

— BE ABLE 1  

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose Ranging Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Bimekizumab in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02905006
• Other study ID #: PS0010
• Secondary ID: 2016-001891-31
• Status: Completed
• Phase: Phase 2
• Start date: August 2016
• Est. completion date: July 2017

Study information

• Verified date: July 2022
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: July 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Plaque Psoriasis
• Psoriasis

Intervention

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

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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
UCB Biopharma S.P.R.L.	Parexel

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Hungary,  Japan,  Poland, 

References & Publications (1)

Gordon KB, Langley RG, Warren RB, Okubo Y, Stein Gold L, Merola JF, Peterson L, Wixted K, Cross N, Deherder D, Thaçi D. Bimekizumab Safety in Patients With Moderate to Severe Plaque Psoriasis: Pooled Results From Phase 2 and Phase 3 Randomized Clinical Tr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 12
Secondary	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.	Week 12
Secondary	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	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.	Week 8
Secondary	Percentage of Participants Achieving a 90% or Higher Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score at 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.	Week 8
Secondary	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.	Week 12
Secondary	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.	Week 12
Secondary	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.	Baseline (Week 0), Week 1, Week 2, Week 4, Week 8, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)
Secondary	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.	From Baseline (Week 0) until Safety Follow-Up Visit (20 weeks after the last dose; Up to Week 28)
Secondary	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.	From Baseline (Week 0) until Safety Follow-Up Visit (20 weeks after the last dose; Up to Week 28)
Secondary	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.	From Baseline (Week 0) until Safety Follow-Up Visit (20 weeks after the last dose; Up to Week 28)
Secondary	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).	Baseline (Week 0)
Secondary	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.	From Week 4 until the Safety Follow-Up visit (20 weeks after the last dose; Up to Week 28)
Secondary	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.	From Screening to End of Safety Follow-up (up to Week 32)
Secondary	Percentage of Participants With at Least One Adverse Event (AE) During the Study by Severity	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.	From Screening to End of Safety Follow-up (up to Week 32)
Secondary	Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Platelets)	Platelets was measured in number of platelets per liter (10^9/L).	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)
Secondary	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).	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)
Secondary	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).	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)
Secondary	Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Erythrocytes Mean Corpuscular Volume)	Erythrocytes mean corpuscular volume was measured in femtolitres (fL).	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)
Secondary	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).	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)
Secondary	Change From Baseline Until Safety Follow-up Visit in Hematology Parameters (Hematocrit)	Hematocrit was measured in volume percentage (%) of red blood cells in blood.	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)
Secondary	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).	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)
Secondary	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).	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)
Secondary	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).	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)
Secondary	Change From Baseline Until Safety Follow-up Visit in Biochemistry Parameters (Creatinine, Bilirubin)	Creatinine and bilirubin were measured in micromols per liter (µmol/L).	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)
Secondary	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).	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)
Secondary	Change From Baseline Until Safety Follow-up Visit in Urinalysis Parameters (pH)	Urine pH was measured on a pH scale.	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)
Secondary	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.	From Baseline (Week 0) until Week 12
Secondary	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.	From Baseline (Week 0) until Week 12
Secondary	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.	From Baseline (Week 0) until Week 12
Secondary	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.	From Baseline (Week 0) until Week 12
Secondary	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.	From Baseline (Week 0) until Week 12
Secondary	Change From Baseline Until Safety Follow-up Visit in Vital Signs (Blood Pressure)	Blood pressure was measured in millimeters of mercury (mmHg).	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)
Secondary	Change From Baseline Until Safety Follow-up Visit in Vital Signs (Pulse Rate)	Pulse rate was measured in beats per minute (beats/min).	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)
Secondary	Change From Baseline Until Safety Follow-up Visit in Vital Signs (Temperature)	Temperature was measured in degrees Celsius (°C).	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)
Secondary	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.	At Screening, Week 12/Early Withdrawal Visit and the Safety Follow-Up Visit (20 weeks after the last dose)
Secondary	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.	Baseline (Week 0), Week 2, Week 4, Week 6, Week 12, and Safety Follow-Up visit (20 weeks after the last dose)