Efficacy and Safety Study of Certolizumab Pegol (CZP) Versus Active Comparator and Placebo in Subjects With Plaque Psoriasis (PSO) (CIMPACT)

• ClinicalTrials.gov Identifier: NCT02346240
• Recruitment Status: Completed
• First Posted: January 26, 2015
• Results First Posted: July 18, 2018
• Last Update Posted: April 13, 2020
• Sponsor: UCB Biopharma S.P.R.L.
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma S.P.R.L. )

Tracking Information

• First Submitted Date: January 20, 2015
• First Posted Date: January 26, 2015
• Results First Submitted Date: June 22, 2018
• Results First Posted Date: July 18, 2018
• Last Update Posted Date: April 13, 2020
• Study Start Date: February 11, 2015
• Actual Primary Completion Date: March 22, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 22, 2018)

Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 12 [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: January 20, 2015): Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 12 [ Time Frame: From Baseline to Week 12 ]

Current Secondary Outcome Measures (submitted: June 22, 2018)

• Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 12 [ Time Frame: Week 12 ]
  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.
• Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 12 [ Time Frame: 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.
• Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 16 [ Time Frame: 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.
• Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 16 [ Time Frame: 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.
• Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 16 [ Time Frame: 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.
• Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: January 20, 2015)

• Proportion of subjects who achieve a Physician's Global Assessment (PGA) Clear or Almost Clear response at Week 12 [ Time Frame: From Baseline to Week 12 ]
• Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 16 [ Time Frame: From Baseline to Week 16 ]
• Proportion of subjects who achieve a Physician's Global Assessment (PGA) Clear or Almost Clear response at Week 16 [ Time Frame: From Baseline to Week 16 ]
• Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 48 [ Time Frame: From Baseline to Week 48 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety Study of Certolizumab Pegol (CZP) Versus Active Comparator and Placebo in Subjects With Plaque Psoriasis (PSO)
• Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo- and Active-Controlled Study Followed by a Placebo-Controlled Maintenance Period and Open-Label Follow-Up to Evaluate the Efficacy and Safety of Certolizumab Pegol in Subjects With Moderate to Severe Chronic Plaque Psoriasis
• Brief Summary: The purpose of this study is to investigate the efficacy and safety of two dose levels of certolizumab pegol compared to active comparator and placebo in adults with moderate to severe chronic plaque psoriasis.

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 Extension Treatment Period (96 weeks)
• Safety Follow-Up (10 weeks)

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Psoriasis
• Plaque Psoriasis

Intervention

• 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
  • CDP870
  • CZP
• Biological: Etanercept
  • Active Substance: Etanercept
  • Pharmaceutical Form: Solution for injection in pre-filled syringe
  • Concentration: 50 mg / mL
  • Route of Administration: Subcutaneous use
  Other Names:

  • Enbrel
  • ETN
• Other: Placebo
  • Active Substance: Placebo
  • Pharmaceutical Form: Solution for injection in pre-filled syringe
  • Concentration: 0.9 % saline
  • Route of Administration: Subcutaneous use
  Other Name: PBO

Study Arms

• Experimental: CZP 200 mg

  Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by CZP 200 mg every two weeks (Q2W) from Week 6 to Week 14.

  The treatment received from Week 16 to Week 48 is based on initial treatment and response to treatment at Week 16:

  • Subjects with a PASI75 response at Week 16 will be re-randomized to receive either CZP 200 mg Q2W or CZP 400 mg every 4 weeks (Q4W; with Placebo administered on alternate dosing weeks to maintain the blind) or Placebo Q2W.
  • Subjects who do not achieve a PASI75 response 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.

  Subjects can enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

  Intervention: Biological: Certolizumab Pegol
• Experimental: CZP 400 mg

  Certolizumab Pegol subcutaneous (sc) injection 400 mg every two weeks (Q2W) through Week 14.

  The treatment received from Week 16 to Week 48 is based on initial treatment and response to treatment at Week 16:

  • Subjects with a PASI75 response at Week 16 will be re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W.
  • Subjects who do not achieve a PASI75 response 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.

  Subjects can enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

  Intervention: Biological: Certolizumab Pegol
• Active Comparator: Etanercept

  Etanercept (ETN) subcutaneous (sc) injection 50 mg twice weekly through Week 12.

  The treatment received from Week 16 to Week 48 is based on initial treatment and response to treatment at Week 16:

  • Subjects with a PASI75 response at Week 16 will be re-randomized to either Certolizumab Pegol (loading dose of 400 mg at Weeks 16, 18, and 20 followed by 200 mg Q2W) or Placebo Q2W.
  • Subjects who do not achieve a PASI75 response 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.

  Subjects can enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

  Intervention: Biological: Etanercept
• Placebo Comparator: Placebo

  Placebo subcutaneous (sc) injection every two weeks (Q2W).

  The treatment received from Week 16 to Week 48 is based on initial treatment and response to treatment at Week 16:

  • Subjects with a PASI75 response at Week 16 continue to receive blinded Placebo.
  • Subjects who do not achieve a PASI75 response 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.

  Subjects can enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

  Intervention: Other: Placebo

• Publications *: Lebwohl M, Blauvelt A, Paul C, Sofen H, Węgłowska J, Piguet V, Burge D, Rolleri R, Drew J, Peterson L, Augustin M. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placebo-controlled study (CIMPACT). J Am Acad Dermatol. 2018 Aug;79(2):266-276.e5. doi: 10.1016/j.jaad.2018.04.013. Epub 2018 Apr 14.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 14, 2016): 559
• Original Estimated Enrollment (submitted: January 20, 2015): 540
• Actual Study Completion Date: December 17, 2018
• Actual Primary Completion Date: March 22, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 the UK, Czech Republic, Germany, and France, and within 3 months for all other countries. Male subjects who are planning a partner pregnancy during the study or within 5 months following the last dose in France and within 10 weeks in all other countries
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Czechia, France, Germany, Hungary, Netherlands, Poland, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT02346240
• Other Study ID Numbers: PS0003; 2014-003492-36 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Responsible Party: UCB Pharma ( UCB Biopharma S.P.R.L. )
• Study Sponsor: UCB Biopharma S.P.R.L.
• Collaborators: Not Provided

Investigators

• Study Director: UCB Cares; +1 844 599 2273 (UCB)

• PRS Account: UCB Pharma
• Verification Date: March 2020