A Study to Evaluate the Pharmacokinetics (PK), Pharmacodynamics (PD), and Safety of Bimekizumab in Patients With Chronic Plaque Psoriasis

• ClinicalTrials.gov Identifier: NCT03025542
• Recruitment Status: Completed
• First Posted: January 19, 2017
• Results First Posted: January 6, 2021
• Last Update Posted: October 28, 2022
• Sponsor: UCB Biopharma SRL
• Collaborator: Parexel
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma SRL )

Study Description

Brief Summary:

This is a Phase 2a, multicenter, randomized, subject-blind, investigator-blind, study to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of bimekizumab in adult subjects with moderate to severe chronic plaque psoriasis

Condition or disease	Intervention/treatment	Phase
Chronic Plaque Psoriasis	Drug: Bimekizumab; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: This is an Investigator- and Subject-blind study.
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Subject-Blind, Investigator-Blind Study to Evaluate the Time Course of Pharmacodynamic Response, Safety and Pharmacokinetics of Bimekizumab in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis
• Actual Study Start Date: December 27, 2016
• Actual Primary Completion Date: December 11, 2017
• Actual Study Completion Date: December 11, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment Arm 1; Subjects randomized in this arm will receive a combination of Bimekizumab and Placebo injections.	Drug: Bimekizumab; Based on their randomization subjects will receive a combination of several injections of Bimekizumab.; Other Name: UCB4940; Other: Placebo; Subjects will receive injections of Placebo.
Experimental: Treatment Arm 2; Subjects randomized in this arm will receive Bimekizumab injections.	Drug: Bimekizumab; Based on their randomization subjects will receive a combination of several injections of Bimekizumab.; Other Name: UCB4940

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Psoriasis Area and Severity Index (PASI) at Week 28 [ Time Frame: From Baseline to Week 28 ]
   The PASI is the most commonly used and validated assessment for grading the severity of psoriasis in clinical studies. The PASI quantifies the severity and extent of the disease and weighs these with the percentage of body surface area (BSA) involvement. The percent area of involvement (BSA%) is estimated across 4 body areas; head (10%), upper limbs (20%), trunk (30%), and lower limbs (40%) and then transferred into a grade. The Investigator assesses the average redness, thickness, and scaliness of lesions in each body area (each on a 5 point scale); 0=none, 1=slight, 2=moderate, 3=marked, and 4=very marked. The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity.
2. Plasma Concentration of Bimekizumab at Baseline [ Time Frame: at Baseline ]
   Plasma concentration was expressed as geometric mean concentrations (GMCs) and measured in micrograms per milliliter (μg/mL). Note: Means, Lower confidence interval (LCI), Upper confidence interval (UCI) are only calculated if at least 2/3 of the concentrations were quantified at the respective time point. Values below limit of quantification (BLQ) are replaced by value of lower limit of quantification (LLOQ)/2 (=0.075ug/mL) in calculations of means.
3. Plasma Concentration of Bimekizumab at Week 2 [ Time Frame: at Week 2 ]
   Plasma concentration was expressed as geometric mean concentrations (GMCs) and measured in micrograms per milliliter (μg/mL). Note: Means, Lower confidence interval (LCI), Upper confidence interval (UCI) are only calculated if at least 2/3 of the concentrations were quantified at the respective time point. Values below limit of quantification (BLQ) are replaced by value of lower limit of quantification (LLOQ)/2 (=0.075ug/mL) in calculations of means.
4. Plasma Concentration of Bimekizumab at Week 4 [ Time Frame: at Week 4 ]
   Plasma concentration was expressed as geometric mean concentrations (GMCs) and measured in micrograms per milliliter (μg/mL). Note: Means, Lower confidence interval (LCI), Upper confidence interval (UCI) are only calculated if at least 2/3 of the concentrations were quantified at the respective time point. Values below limit of quantification (BLQ) are replaced by value of lower limit of quantification (LLOQ)/2 (=0.075ug/mL) in calculations of means.
5. Plasma Concentration of Bimekizumab at Week 8 [ Time Frame: at Week 8 ]
   Plasma concentration was expressed as geometric mean concentrations (GMCs) and measured in micrograms per milliliter (μg/mL). Note: Means, Lower confidence interval (LCI), Upper confidence interval (UCI) are only calculated if at least 2/3 of the concentrations were quantified at the respective time point. Values below limit of quantification (BLQ) are replaced by value of lower limit of quantification (LLOQ)/2 (=0.075ug/mL) in calculations of means.
6. Plasma Concentration of Bimekizumab at Week 12 [ Time Frame: at Week 12 ]
   Plasma concentration was expressed as geometric mean concentrations (GMCs) and measured in micrograms per milliliter (μg/mL). Note: Means, Lower confidence interval (LCI), Upper confidence interval (UCI) are only calculated if at least 2/3 of the concentrations were quantified at the respective time point. Values below limit of quantification (BLQ) are replaced by value of lower limit of quantification (LLOQ)/2 (=0.075ug/mL) in calculations of means.
7. Plasma Concentration of Bimekizumab at Week 16 [ Time Frame: at Week 16 ]
   Plasma concentration was expressed as geometric mean concentrations (GMCs) and measured in micrograms per milliliter (µg/mL). Note: Means, Lower confidence interval (LCI), Upper confidence interval (UCI) are only calculated if at least 2/3 of the concentrations were quantified at the respective time point. Values below limit of quantification (BLQ) are replaced by value of lower limit of quantification (LLOQ)/2 (=0.075ug/mL) in calculations of means.
8. Plasma Concentration of Bimekizumab at Week 20 [ Time Frame: at Week 20 ]
   Plasma concentration was expressed as geometric mean concentrations (GMCs) and measured in micrograms per milliliter (μg/mL). Note: Means, Lower confidence interval (LCI), Upper confidence interval (UCI) are only calculated if at least 2/3 of the concentrations were quantified at the respective time point. Values below limit of quantification (BLQ) are replaced by value of lower limit of quantification (LLOQ)/2 (=0.075ug/mL) in calculations of means.
9. Plasma Concentration of Bimekizumab at Week 24 [ Time Frame: at Week 24 ]
   Plasma concentration was expressed as geometric mean concentrations (GMCs) and measured in micrograms per milliliter (μg/mL). Note: Means, Lower confidence interval (LCI), Upper confidence interval (UCI) are only calculated if at least 2/3 of the concentrations were quantified at the respective time point. Values below limit of quantification (BLQ) are replaced by value of lower limit of quantification (LLOQ)/2 (=0.075ug/mL) in calculations of means.
10. Plasma Concentration of Bimekizumab at Week 28 [ Time Frame: at Week 28 ]
    Plasma concentration was expressed as geometric mean concentrations (GMCs) and measured in micrograms per milliliter (μg/mL). Note: Means, Lower confidence interval (LCI), Upper confidence interval (UCI) are only calculated if at least 2/3 of the concentrations were quantified at the respective time point. Values below limit of quantification (BLQ) are replaced by value of lower limit of quantification (LLOQ)/2 (=0.075ug/mL) in calculations of means.
11. Plasma Concentration of Bimekizumab at Week 36 [ Time Frame: at Week 36 ]
    Plasma concentration was expressed as geometric mean concentrations (GMCs) and measured in micrograms per milliliter (μg/mL). Note: Means, Lower confidence interval (LCI), Upper confidence interval (UCI) are only calculated if at least 2/3 of the concentrations were quantified at the respective time point. Values below limit of quantification (BLQ) are replaced by value of lower limit of quantification (LLOQ)/2 (=0.075ug/mL) in calculations of means.
12. Percentage of Participants Reporting Positive Anti-Drug-Antibodies (ADA) Titre Prior to Study Treatment With Bimekizumab at Baseline [ Time Frame: at Baseline ]
    An ADA status of positive was concluded for any participant with an ADA level that was above cut point (ACP) and 'confirmed positive' (CP) at any time point. A participant was classified as having treatment-induced ADA positivity when meeting one of the following criteria: -The Baseline result was either below cut point (BCP) or ACP and 'not confirmed positive' (NCP), and at least 1 post Baseline time point was ACP and CP. -The Baseline result was positive (ACP and CP) and at least one post-Baseline measurement showed a pre-defined fold increase in titre from the Baseline value. Note: The overall status of a participant is 'Positive' if at any post-Baseline visit the result was ACP and confirmed positive.
13. Percentage of Participants Reporting an Overall Positive Anti-Drug-Antibodies (ADA) Titre Following Study Treatment With Bimekizumab [ Time Frame: From Baseline to Safety Follow-Up Visit (Week 36) ]
    An ADA status of positive was concluded for any participant with an ADA level that was above cut point (ACP) and 'confirmed positive' (CP) at any time point. A participant was classified as having treatment-induced ADA positivity when meeting one of the following criteria: -The Baseline result was either below cut point (BCP) or ACP and 'not confirmed positive' (NCP), and at least 1 post Baseline time point was ACP and CP. -The Baseline result was positive (ACP and CP) and at least one post-Baseline measurement showed a pre-defined fold increase in titre from the Baseline value. Note: The overall status of a participant is 'Positive' if at any post-Baseline visit the result was ACP and confirmed positive.
14. Percentage of Participants Who Experienced at Least One Adverse Events (AEs) [ Time Frame: From Screening to Safety Follow-Up Visit (Week 36) ]
    An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Within the Safety Set, this trial reported a total of 164 occurences of adverse events, of which 7 were pre-treatment adverse events and 157 were treatment-emergent adverse events (TEAEs).

Secondary Outcome Measures :

1. Percentage of Participants Achieving a 75% or Higher Improvement From Baseline in PASI (Psoriasis Area and Severity Index) Score at Week 16 [ Time Frame: From Baseline to Week 16 ]
   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.
2. Percentage of Participants Achieving a 90% or Higher Improvement From Baseline in PASI (Psoriasis Area and Severity Index) Score at Week 16 [ Time Frame: From Baseline to Week 16 ]
   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.
3. Percentage of Participants Achieving a 100% Improvement From Baseline in PASI (Psoriasis Area and Severity Index) Score at Week 16 [ Time Frame: From Baseline to Week 16 ]
   The PASI100 response assessments are based on at least 100% 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.
4. Percentage of Participants With IGA (Investigator´s Global Assessment) Response at Week 16 [ Time Frame: at Week 16 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female at least 18 years of age and less than or equal to 70
• Chronic plaque psoriasis for at least 6 months prior to Screening
• Psoriasis Area and Severity Index (PASI) >=12 and body surface area (BSA) >=10% and Investigator's Global Assessment (IGA) score >=3 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, and have a negative pregnancy test at Visit 1 (Screening) and immediately prior to first dose
• 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 (anticipated 5 half-lives)

Exclusion Criteria:

• Subjects previously participating in a bimekizumab study
• Subjects with erythrodermic, guttate, pustular form of psoriasis, or drug-induced psoriasis
• History of chronic or recurrent infections, or a serious or life-threatening infection within the 6 months prior to the Baseline Visit (including herpes zoster)
• High risk of infection in the Investigator's opinion
• Current sign or symptom that may indicate an active infection
• Concurrent acute or chronic viral hepatitis B or C or human immunodeficiency virus (HIV) infection
• Live (includes attenuated) vaccination within the 8 weeks prior to Baseline
• Subjects with concurrent malignancy or history of malignancy during the past 5 years (except for specific malignant condition as defined in the protocol)
• Primary immunosuppressive conditions
• TB infection, high risk of acquiring TB infection, latent TB infection (LTBI), or current or history of NTMB infection
• Laboratory abnormalities, as defined in the study protocol
• Any condition which, in the Investigator's judgement, would make the subject unsuitable for inclusion in the study
• Exposure to more than 1 biological response modifier (limited to anti-TNF or IL-12/-23) or any biologic response modifier during the three months prior to the Baseline Visit
• Subjects have received previous treatment with any anti-IL-17 therapy for the treatment of psoriasis or psoriatic arthritis
• Subjects with a diagnosis of inflammatory conditions other than psoriasis or psoriatic arthritis, including but not limited to rheumatoid arthritis, sarcoidosis, or systemic lupus erythematosus. Subjects with a diagnosis of Crohn's disease or ulcerative colitis are allowed as long as they have no active symptomatic disease at Screening or Baseline
• Subjects taking psoriatic arthritis medications other than nonsteroidal anti-inflammatory drugs (NSAIDs) or analgesics

Contacts and Locations

Locations

United States, Ohio

Ps0016 704

Bexley, Ohio, United States

Australia

Ps0016 102

Kogarah, Australia

Ps0016 101

Melbourne, Australia

Ps0016 104

Woolloongabba, Australia

Canada

Ps0016 201

Ajax, Canada

Ps0016 203

London, Canada

Ps0016 202

Windsor, Canada

Moldova, Republic of

Ps0016 501

Chisinau, Moldova, Republic of

Sponsors and Collaborators

UCB Biopharma SRL

Parexel

Investigators

• Study Director: UCB Cares; 001 844 599 2273(UCB)

  Study Documents (Full-Text)

Documents provided by UCB Pharma ( UCB Biopharma SRL ):

Study Protocol  [PDF] September 23, 2016

Statistical Analysis Plan  [PDF] November 30, 2017

More Information

Additional Information:

Product Information 

FDA Safety Alerts and Recalls 

Publications of Results:

Oliver R, Krueger JG, Glatt S, Vajjah P, Mistry C, Page M, Edwards H, Garcet S, Li X, Dizier B, Maroof A, Watling M, El Baghdady A, Baeten D, Ionescu L, Shaw S. Bimekizumab for the treatment of moderate-to-severe plaque psoriasis: efficacy, safety, pharmacokinetics, pharmacodynamics and transcriptomics from a phase IIa, randomized, double-blind multicentre study. Br J Dermatol. 2022 Apr;186(4):652-663. doi: 10.1111/bjd.20827. Epub 2021 Dec 27.

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.

• Responsible Party: UCB Biopharma SRL
• ClinicalTrials.gov Identifier: NCT03025542
• Other Study ID Numbers: PS0016; 2016-002368-15 ( EudraCT Number )
• First Posted: January 19, 2017
• Results First Posted: January 6, 2021
• Last Update Posted: October 28, 2022
• Last Verified: September 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by UCB Pharma ( UCB Biopharma SRL ):

Psoriasis; Chronic Plaque Psoriasis; Bimekizumab

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases