An Efficacy and Safety Study of Two Dose Levels of Certolizumab Pegol (CZP) in Subjects With Plaque Psoriasis (PSO) (CIMPASI-1)

A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Group, Study Followed by a Dose-Blind Period and Open-Label Follow-Up to Evaluate the Efficacy and Safety of Certolizumab Pegol in Subjects With Moderate to Severe Chronic Plaque Psoriasis

The purpose of this study is to investigate the efficacy and safety of two dose levels of certolizumab pegol in adults with moderate to severe chronic plaque psoriasis when administered every 2 weeks.

Study Overview

• Status: Completed
• Conditions: Psoriasis; Plaque Psoriasis
• Intervention / Treatment: Biological: Certolizumab Pegol; Other: Placebo

Detailed Description

This study consists of the following Periods:

• Initial Treatment Period from Week 0 to Week 16
• Maintenance Treatment Period from Week 16 to Week 48
• Open-label Treatment Period from Week 48 to Week 144
• Safety Follow-Up Period from Week 144 to Week 152

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • Ps0005 597
  • British Columbia
    • Surrey, British Columbia, Canada
      • Ps0005 591
  • Ontario
    • Ajax, Ontario, Canada
      • Ps0005 596
    • Hamilton, Ontario, Canada
      • Ps0005 590
    • Toronto, Ontario, Canada
      • Ps0005 593
  • Quebec
    • Drummondville, Quebec, Canada
      • Ps0005 595
    • Quebec City, Quebec, Canada
      • Ps0005 594
• Czechia
  • Nachod, Czechia
    • Ps0005 553
  • Olomouc, Czechia
    • Ps0005 550
  • Ostrava-Poruba, Czechia
    • Ps0005 551
  • Praha 10, Czechia
    • Ps0005 552
• Germany
  • Berlin, Germany
    • Ps0005 560
  • Dresden, Germany
    • Ps0005 561
  • Hamburg, Germany
    • Ps0005 563
  • Hamburg, Germany
    • Ps0005 568
  • Kiel, Germany
    • Ps0005 566
  • Brandenburg
    • Mahlow, Brandenburg, Germany
      • Ps0005 562
  • Nordrhein-Westfalen
    • Witten, Nordrhein-Westfalen, Germany
      • Ps0005 565
  • Schleswig-Holstein
    • Lubeck, Schleswig-Holstein, Germany
      • Ps0005 569
• Hungary
  • Budapest, Hungary
    • Ps0005 582
  • Pecs, Hungary
    • Ps0005 581
  • Bekes
    • Orosháza, Bekes, Hungary
      • Ps0005 580
• United States
  • California
    • San Diego, California, United States, 92123
      • Ps0005 504
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Ps0005 502
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Ps0005 500
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Ps0005 506
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Ps0005 505
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Ps0005 507
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Ps0005 508
  • Texas
    • Houston, Texas, United States, 77004
      • Ps0005 501

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provided informed consent
• Adult men or women >= 18 years
• Chronic plaque psoriasis for at least 6 months
• Baseline psoriasis activity and severity index >= 12 and body surface area >= 10 % and Physician's Global Assessments score >= 3
• Candidate for systemic psoriasis therapy and/or phototherapy and/or chemophototherapy
• Other protocol-defined inclusion criteria may apply

Exclusion Criteria:

• Erythrodermic, guttate, generalized pustular form of psoriasis
• History of current, chronic, or recurrent infections of viral, bacterial, or fungal origin as described in the protocol
• Congestive heart failure
• History of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease
• Concurrent malignancy or a history of malignancy as described in the protocol
• History of, or suspected, demyelinating disease of the central nervous system (e.g., multiple sclerosis or optic neuritis)
• Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study or within 5 months following last dose of study drug (in Czech Republic and Germany) and within 3 months for all other countries. Male subjects who are planning a partner pregnancy during the study or within 10 weeks following the last dose of study drug
• Any other condition which, in the Investigator's judgment, would make the subject unsuitable for participation in the study
• 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
Experimental: CZP 200 mg; CZP 400 mg at Weeks 0, 2, 4, followed by CZP 200 mg every two weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment: PASI50 responders at Week 16 continue to receive CZP 200 mg Q2W.; PASI50 non-responders at Week 16 will be removed from blinded study medication and escape to unblinded CZP 400 mg Q2W. Subjects who receive unblinded CZP 400 mg Q2W for 16 weeks and do not achieve a PASI50 response will be withdrawn from the study.; PASI50 non-responders at Week 32 or a later time point will be withdrawn from the study. Subjects who complete the Maintenance Period (with PASI50 response at Week 48) enter the Open-label Extension Period on CZP 200 mg Q2W. Week 48 completers in the escape arm continue to receive CZP 400 mg Q2W or may switch to CZP 200 mg Q2W. Depending on PASI50 or PASI75 responses at Week 60 or a later time point, subjects may switch to CZP 400 mg Q2W or withdraw from the study.	Biological: Certolizumab Pegol; Active Substance: 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; CZP 400 mg every two weeks (Q2W) through Week 14. Treatment received from Week 16 - 48 is based on initial treatment and response to treatment: PASI50 responders at Week 16 continue to receive CZP 400 mg Q2W.; PASI50 non-responders at Week 16 will be removed from blinded study medication and escape to CZP 400 mg Q2W. Subjects who receive unblinded CZP 400 mg Q2W for 16 weeks and do not achieve a PASI50 response will be withdrawn from the study.; PASI50 non-responders at Week 32 or a later time point will be withdrawn from the study. Subjects who complete the Maintenance Period (with PASI50 response at Week 48) enter the Open-label Extension (OLE) Period on CZP 200 mg Q2W. Week 48 completers in the escape arm continue to receive CZP 400 mg Q2W or may switch to CZP 200 mg Q2W. Subjects who achieve a PASI75 response during the OLE Phase may switch to CZP 200 mg Q2W.	Biological: Certolizumab Pegol; Active Substance: 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
Placebo Comparator: Placebo; Placebo subcutaneous (sc) injection every two weeks (Q2W). Treatment received from Week 16 - 48 is based on initial treatment and response to treatment: PASI50 responders at Week 16, who do not achieve a PASI75 response at Week 16 receive CZP 400 mg at Weeks 16, 18 and 20 (loading doses) followed by CZP 200 mg Q2W starting at Week 22.; PASI75 responders at Week 16 continue to receive Placebo.; PASI50 non-responders at Week 16 will be removed from blinded study medication and escape to CZP 400 mg Q2W. Subjects who receive unblinded CZP 400 mg Q2W for 16 weeks and do not achieve a PASI50 response will be withdrawn from the study.; PASI50 non-responders at Week 32 or a later time point will be withdrawn from the study. Subjects who complete the Maintenance Period (with PASI50 response at Week 48) enter the Open-label Extension Period on CZP 200 mg Q2W. Week 48 completers in the escape arm continue to receive CZP 400 mg Q2W or may switch to CZP 200 mg Q2W.	Other: Placebo; Active Substance: Placebo; Pharmaceutical Form: Solution for injection in pre-filled syringe; Concentration: 0.9 % saline; Route of Administration: Subcutaneous use; Other Names: PBO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at 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.	At Week 16
Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear (With at Least 2-category Improvement) Response at Week 16	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.	At Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at 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.	At Week 16
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16	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 asks 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 of 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).	At Week 16
Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear (With at Least 2-category Improvement) Response at Week 48	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.	At Week 48
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48	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.	At Week 48

Collaborators and Investigators

• Sponsor: UCB Biopharma S.P.R.L.

Publications and helpful links

General Publications

• Gottlieb AB, Blauvelt A, Thaci D, Leonardi CL, Poulin Y, Drew J, Peterson L, Arendt C, Burge D, Reich K. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2). J Am Acad Dermatol. 2018 Aug;79(2):302-314.e6. doi: 10.1016/j.jaad.2018.04.012. Epub 2018 Apr 13.
• Gordon KB, Warren RB, Gottlieb AB, Blauvelt A, Thaci D, Leonardi C, Poulin Y, Boehnlein M, Brock F, Ecoffet C, Reich K. Long-term efficacy of certolizumab pegol for the treatment of plaque psoriasis: 3-year results from two randomized phase III trials (CIMPASI-1 and CIMPASI-2). Br J Dermatol. 2021 Apr;184(4):652-662. doi: 10.1111/bjd.19393. Epub 2020 Sep 9.
• Blauvelt A, Paul C, van de Kerkhof P, Warren RB, Gottlieb AB, Langley RG, Brock F, Arendt C, Boehnlein M, Lebwohl M, Reich K. Long-term safety of certolizumab pegol in plaque psoriasis: pooled analysis over 3 years from three phase III, randomized, placebo-controlled studies. Br J Dermatol. 2021 Apr;184(4):640-651. doi: 10.1111/bjd.19314. Epub 2020 Sep 6.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2014
• Primary Completion (Actual): March 8, 2016
• Study Completion (Actual): October 24, 2018

Study Registration Dates

• First Submitted: December 22, 2014
• First Submitted That Met QC Criteria: December 22, 2014
• First Posted (Estimate): December 29, 2014

Study Record Updates

• Last Update Posted (Actual): November 7, 2019
• Last Update Submitted That Met QC Criteria: October 23, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Psoriasis; Cimzia; Certolizumab Pegol
• 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: PS0005; 2014-003513-28 (EudraCT Number)

Drug and device information, study documents

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