A Study to Test the Efficacy and Safety of Certolizumab Pegol in Japanese Subjects With Moderate to Severe Chronic Psoriasis

Phase 2/3, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study To Evaluate the Efficacy and Safety of Certolizumab Pegol in Japanese Subjects With Moderate to Severe Chronic Psoriasis

The purpose of this study is to demonstrate the efficacy and safety of Certolizumab Pegol (CZP) in the treatment of moderate to severe chronic plaque Psoriasis (PSO) in Japanese subjects.

Study Overview

• Status: Completed
• Conditions: Moderate to Severe Psoriasis; Generalized Pustular Psoriasis and Erythrodermic Psoriasis
• Intervention / Treatment: Other: Placebo; Drug: Certolizumab Pegol

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Japan
  • Asahikawa, Japan
    • Ps0017 024
  • Bunkyo-Ku, Japan
    • Ps0017 012
  • Chiyoda-Ku, Japan
    • Ps0017 010
  • Chūōku, Japan
    • Ps0017 007
  • Fukuoka, Japan
    • Ps0017 004
  • Fukushima, Japan
    • Ps0017 039
  • Gifu, Japan
    • Ps0017 028
  • Hamamatsu, Japan
    • Ps0017 040
  • Itabashi-Ku, Japan
    • Ps0017 013
  • Kobe, Japan
    • Ps0017 022
  • Kumamoto, Japan
    • Ps0017 032
  • Kurume, Japan
    • Ps0017 031
  • Kyoto, Japan
    • Ps0017 021
  • Matsumoto, Japan
    • Ps0017 041
  • Minatoku, Japan
    • Ps0017 009
  • Miyazaki, Japan
    • Ps0017 033
  • Nagoya, Japan
    • Ps0017 016
  • Nankoku, Japan
    • Ps0017 029
  • Obihiro, Japan
    • Ps0017 005
  • Osaka, Japan
    • Ps0017 017
  • Osaka, Japan
    • Ps0017 042
  • Osaka-Sayama, Japan
    • Ps0017 037
  • Sapporo, Japan
    • Ps0017 001
  • Sendai, Japan
    • Ps0017 027
  • Shimotsuke, Japan
    • Ps0017 015
  • Shinagawa-Ku, Japan
    • Ps0017 008
  • Shinjuku, Japan
    • Ps0017 002
  • Shinjuku, Japan
    • Ps0017 003
  • Shinjuku, Japan
    • Ps0017 011
  • Shinjuku, Japan
    • Ps0017 014
  • Sumida, Japan
    • Ps0017 034
  • Takaoka, Japan
    • Ps0017 038
  • Tsu, Japan
    • Ps0017 025

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is male or female, >= 20 years of age.
• Institutional Review Board-approved written informed consent form is signed and dated by the subject.
• Other protocol-defined inclusion criteria may apply.

For subjects with moderate to severe chronic plaque psoriasis (PSO)

• Chronic plaque psoriasis for at least 6 months.
• Baseline Psoriasis Activity and Severity Index (PASI) >=12 and Body Surface Area (BSA) affected by PSO >=10% and Physician's Global Assessment (PGA) score of 3 or higher.
• Candidates for systemic PSO therapy and/or phototherapy and/or chemophototherapy.

For subjects with generalized pustular PSO or erythrodermic PSO

• Diagnosis of generalized pustular PSO or erythrodermic PSO at Screening.
• History of plaque-type PSO if subjects have a diagnosis of erythrodermic PSO.
• Baseline BSA affected by PSO >=80% if subjects have a diagnosis of erythrodermic PSO.

Exclusion Criteria:

• Female subject who is breastfeeding, pregnant, or plans to become pregnant during the study or within 5 months following last dose of study drug. Male subject who is planning a partner pregnancy during the study or within 5 months following the last dose of study drug.
• Subject has guttate psoriasis or drug-induced psoriasis. For subjects with moderate to severe plaque psoriasis, erythrodermic or pustular forms of psoriasis also are excluded.
• History of current, chronic, or recurrent infections of viral, bacterial, or fungal origin as described in the protocol. Also, subjects with a high risk of infection in the Investigator's opinion.
• History of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease.
• History of other malignancy or concurrent malignancy as described in the protocol.
• Class III or IV congestive heart failure
• History of, or suspected, demyelinating disease of the central nervous system (e.g., multiple sclerosis or optic neuritis).
• Subject has any other condition which, in the Investigator's judgment, would make the subject unsuitable for inclusion in the study.
• Concurrent medication restrictions as described in the protocol.
• Subject with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or with untreated latent tuberculosis infection (LTBI) or current or history of nontuberculous mycobacterial (NTMB) infection.
• Subject has any protocol defined clinically significant laboratory abnormalities at the screening
• Other protocol-defined exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo subcutaneous (sc) injection every two weeks (Q2W)	Other: Placebo; Pharmaceutical Form: Solution for injection in pre-filled syringe; Concentration: 0.9 % saline; Route of Administration: Subcutaneous use Q2W; Other Names: PBO
Experimental: CZP 200 mg; Certolizumab Pegol subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by Certolizumab Pegol subcutaneous (sc) injection 200 mg every two weeks (Q2W) with PBO administered to maintain the blind, starting at Week 6	Other: Placebo; Pharmaceutical Form: Solution for injection in pre-filled syringe; Concentration: 0.9 % saline; Route of Administration: Subcutaneous use Q2W; Other Names: PBO; Drug: Certolizumab Pegol; Pharmaceutical Form: Solution for injection in pre-filled syringe; Concentration: 200 mg/mL; Route of Administration: Subcutaneous use; Other Names: Cimzia; CZP; CDP870
Experimental: CZP 400 mg; Certolizumab Pegol subcutaneous (sc) injection 400 mg every two weeks (Q2W).	Drug: Certolizumab Pegol; Pharmaceutical Form: Solution for injection in pre-filled syringe; Concentration: 200 mg/mL; Route of Administration: Subcutaneous use; Other Names: Cimzia; CZP; CDP870

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Achieving a 75 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16	The PASI75 response assessments were 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 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2-category Improvement) at Week 16	This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The Investigator assessed the overall severity of Psoriasis (PSO) using the following 5-point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe.	Week 16
Percentage of Subjects Achieving a 90 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16	The PASI90 response assessments were 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 16
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16	This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The DLQI is a subject-reported questionnaire designed for use in adult participants with PSO. The DLQI is a skin disease-specific questionnaire aimed at the evaluation of how symptoms and treatment affect patients' health related quality of life (HRQoL). This instrument asked participants about symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. It has been shown to be valid and reproducible in PSO patients. The DLQI score ranges from 0 to 30 with higher scores indicating lower HRQoL. A higher than or equal to (>=) 4-point change in the DLQI score (DLQI response) has been reported to be meaningful for the patient (within-patient minimal important difference Basra et al, 2015) a DLQI absolute score of lower than or equal to (=<) 1 indicates DLQI remission (i.e., no or small impact of the disease on HRQoL).	Baseline and Week 16
Change From Baseline in Itch Numeric Rating Scale at Week 16	This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The Itch Numeric Rating Scale (NRS) has been developed as a simple, single item instrument to assess the patient-reported severity of itch at its most intense during the past 24h period. Participants indicate itch severity by circling the integer that best describes the worst level of itching due to PSO in the past 24h period on an 11-point scale anchored at 0, representing "no itching" and 10, representing "worst itch imaginable" (Kimball et al, 2016).	Baseline and Week 16
Plasma Concentration of Certolizumab Pegol (CZP)	Plasma concentration was expressed in micrograms per milliliter (μg/mL). Values below Lower Limit of Quantification (LLOQ) were set to half the LLOQ to present summaries. The geometric mean and geometric coefficient of variation were only displayed if at least 2/3 of the data were above the LLOQ.	Blood samples were collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60
Percentage of Participants With Positive Anti-Certolizumab Pegol-antibody Levels in Plasma	A pre-anti-drug (CZP) antibody (ADA) positive subject was defined as having a confirmed positive sample at Baseline. A pre-ADA negative subject was defined as having a Screening below the cut point (BCP) sample, or a screening above the cut point (ACP) sample, but not confirmed positive at Baseline. A treatment-emergent ADA positive subject was defined as either 1) pre-ADA negative subjects having at least 1 ADA confirmed positive sample or 2) pre-ADA positive subjects with at least 1 sample with greater then or equal to (>=) 1.67-fold increase from Baseline on CZP treatment.	Blood samples will be collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60

Collaborators and Investigators

• Sponsor: UCB Biopharma S.P.R.L.

Publications and helpful links

General Publications

• Imafuku S, Tada Y, Umezawa Y, Sakurai S, Hoshii N, Nakagawa H. Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: Effect of Demographics and Baseline Disease Characteristics on Efficacy. Dermatol Ther (Heidelb). 2022 Jan;12(1):121-135. doi: 10.1007/s13555-021-00645-2. Epub 2021 Nov 26.
• Okubo Y, Umezawa Y, Sakurai S, Hoshii N, Nakagawa H. Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis: 52-Week Results. Dermatol Ther (Heidelb). 2022 Jun;12(6):1397-1415. doi: 10.1007/s13555-022-00741-x. Epub 2022 May 27.
• Umezawa Y, Asahina A, Imafuku S, Tada Y, Sano S, Morita A, Sakurai S, Hoshii N, Tilt N, Nakagawa H. Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: 52-Week Results. Dermatol Ther (Heidelb). 2021 Jun;11(3):943-960. doi: 10.1007/s13555-021-00520-0. Epub 2021 Apr 22.
• Umezawa Y, Sakurai S, Hoshii N, Nakagawa H; PS0017 Study Group. Certolizumab Pegol for the Treatment of Moderate to Severe Plaque Psoriasis: 16-Week Results from a Phase 2/3 Japanese Study. Dermatol Ther (Heidelb). 2021 Apr;11(2):513-528. doi: 10.1007/s13555-021-00494-z. Epub 2021 Feb 19.

Helpful Links

• FDA Safety Alerts and Recalls
• Product Information

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2017
• Primary Completion (Actual): November 19, 2018
• Study Completion (Actual): January 16, 2019

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 13, 2017

Study Record Updates

• Last Update Posted (Actual): January 4, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Psoriasis; Cimzia; Chronic plaque psoriasis; PSO; Certolizumb Pegol; Generalized pustular psoriasis and erythrodermic psoriasis
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Certolizumab Pegol
• Other Study ID Numbers: PS0017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No