Certolizumab Pegol in Subjects With Adult Onset Active and Progressive Psoriatic Arthritis

NCT01087788 | Completed Phase 3 Results

• 2 other identifiers: PsA0012009-011720-59
• Study Type: interventional
• Target: 409
• Locations: 15 countries
• Sites: 92

Brief Summary

Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of Certolizumab Pegol (CZP) in subjects with adult onset active and progressive Psoriatic Arthritis (PsA).

Conditions

Arthritis, Psoriatic

Keywords

Certolizumab Pegol; Cimzia

Outcome Measures

Primary Outcomes (2)

• American College of Rheumatology 20 (ACR20) Response at Week 12

  ACR20 responders are those subjects with at least 20 % improvement from Baseline (BL) for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS).

  Week 12

• Change From Baseline in Modified Total Sharp Score (mTSS) in Modification for Psoriatic Arthritis at Week 24

  Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 64 and 52 joints, respectively, with higher scores representing greater damage. mTSS (bone erosions) ranges from 0 (best possible outcome) to 320 (worst possible outcome); mTSS (joint space narrowing) ranges from 0 (best possible outcome) to 208 (worst possible outcome); and total score ranges from 0 (best possible outcome) to 528 (worst possible outcome). For the pre-defined analysis of this outcome measure, 0 was used for Baseline and the maximum observed mTSS value was used for Week 24 for those subjects which had less than 2 radiographs. The re-analysis is restricted to those subjects in the Randomized Set who have at least 2 x-ray values at scheduled visits, which are at least 8 weeks apart.

  From Baseline to Week 24

Secondary Outcomes (4)

• American College of Rheumatology 20 (ACR20) Response at Week 24

  Week 24

• Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24

  From Baseline to Week 24

• Psoriasis Area Severity Index (PASI75) Response at Week 24 in the Subgroup of Subjects With Psoriasis (PSO) Involving at Least 3 % Body Surface Area (BSA) at Baseline

  Week 24

• Change From Baseline in Modified Total Sharp Score (mTSS) at Week 48

  From Baseline to Week 48

Study Arms (7)

CZP 200 mg Q2W

EXPERIMENTAL

Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.

Biological: CZP 200 mg Q2W; Other: Placebo

CZP 400 mg Q4W

EXPERIMENTAL

Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards. Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.

Biological: CZP 400 mg Q4W; Other: Placebo

Placebo

PLACEBO COMPARATOR

Matching Placebo to Certolizumab Pegol (CZP) injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group and were re-randomized to either CZP 200 mg Q2W or CZP 400 mg Q4W arm on Week 16. After 24 weeks, all subjects were re-randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W).

Other: Placebo

Placebo to CZP 200 mg escape on Week 16

OTHER

Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 22 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.

Biological: CZP 200 mg Q2W; Other: Placebo

Placebo to CZP 400 mg escape on Week 16

OTHER

Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 24 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.

Biological: CZP 400 mg Q4W; Other: Placebo

Placebo to CZP 200 mg on Week 24

OTHER

Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 30 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.

Biological: CZP 200 mg Q2W; Other: Placebo

Placebo to CZP 400 mg on Week 24

OTHER

Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 32 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.

Biological: CZP 400 mg Q4W; Other: Placebo

Interventions

CZP 200 mg Q2W BIOLOGICAL

200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).

Also known as: Cimzia, Certolizumab Pegol

CZP 200 mg Q2W; Placebo to CZP 200 mg escape on Week 16; Placebo to CZP 200 mg on Week 24

CZP 400 mg Q4W BIOLOGICAL

400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).

Also known as: Cimzia, Certolizumab Pegol

CZP 400 mg Q4W; Placebo to CZP 400 mg escape on Week 16; Placebo to CZP 400 mg on Week 24

Placebo OTHER

Matching Placebo to CZP injection.

CZP 200 mg Q2W; CZP 400 mg Q4W; Placebo; Placebo to CZP 200 mg escape on Week 16; Placebo to CZP 200 mg on Week 24; Placebo to CZP 400 mg escape on Week 16; Placebo to CZP 400 mg on Week 24

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of adult-onset Psoriatic Arthritis (PsA) of at least 6 months' duration as defined by the Classification Criteria for Psoriatic Arthritis (CASPAR criteria)
• Active Psoriatic Skin Lesions or a documented history of Psoriasis
• Active Arthritis with ≥ 3 tender joints at Screening and Baseline, ≥ 3 swollen joints at Screening and Baseline and fulfilling at least 1 of the following 2 criteria during the Screening Period:
• Erythrocyte Sedimentation Rate (ESR) (Westergren) ≥ 28 mm/hour
• C-reactive protein (CRP) \> Upper Limit Normal (ULN)
• Failure to 1 or more treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

You may not qualify if:

• Diagnosis of any other inflammatory Arthritis or known diagnosis of Fibromyalgia
• Exposure to more than 1 Tumor Necrosis Factor α (TNFα) antagonist or to more than 2 previous biological response modifiers for PsA or Psoriasis
• Any non-biological systemic treatment of Psoriasis; phototherapy; topical agents
• History of chronic or recurrent infections
• High risk of infection
• Live vaccination within the 8 weeks prior to Baseline
• Concurrent malignancy or a history of malignancy
• Class III or IV congestive Heart Failure - New York Heart Association (NYHA)
• Demyelinating disease of the central nervous system
• Clinically significant laboratory abnormalities

Sponsors & Collaborators

• UCB BIOSCIENCES GmbH: lead

Study Sites (92)

961

Birmingham, Alabama, United States

Location

953

Tuscaloosa, Alabama, United States

Location

954

Peoria, Arizona, United States

Location

971

Scottsdale, Arizona, United States

Location

966

Palm Desert, California, United States

Location

952

San Diego, California, United States

Location

957

Aventura, Florida, United States

Location

962

Fort Lauderdale, Florida, United States

Location

959

Orange Park, Florida, United States

Location

958

Vero Beach, Florida, United States

Location

964

Hagerstown, Maryland, United States

Location

960

Kalamazoo, Michigan, United States

Location

969

Eagan, Minnesota, United States

Location

984

Flowood, Mississippi, United States

Location

965

Florissant, Missouri, United States

Location

950

St Louis, Missouri, United States

Location

985

Brooklyn, New York, United States

Location

963

Asheville, North Carolina, United States

Location

976

Cleveland, Ohio, United States

Location

951

Middleburg Heights, Ohio, United States

Location

970

Oklahoma City, Oklahoma, United States

Location

982

Portland, Oregon, United States

Location

972

Duncansville, Pennsylvania, United States

Location

975

Dallas, Texas, United States

Location

978

Houston, Texas, United States

Location

967

San Antonio, Texas, United States

Location

968

Seattle, Washington, United States

Location

700

Buenos Aires, Argentina

Location

704

Buenos Aires, Argentina

Location

707

Buenos Aires, Argentina

Location

705

Córdoba, Argentina

Location

706

Rosario, Argentina

Location

710

San Juan, Argentina

Location

702

San Miguel de Tucumán, Argentina

Location

708

San Miguel de Tucumán, Argentina

Location

152

Ghent, Belgium

Location

151

Liège, Belgium

Location

750

Curitiba, Brazil

Location

757

Goiás, Brazil

Location

761

Goiâna, Brazil

Location

753

Porto Alegre, Brazil

Location

907

Victoria, British Columbia, Canada

Location

900

St. John's, Newfoundland and Labrador, Canada

Location

904

Toronto, Ontario, Canada

Location

910

Windsor, Ontario, Canada

Location

905

Trois-Rivires, Quebec, Canada

Location

504

Brno, Czechia

Location

501

Hlučín, Czechia

Location

500

Pardubice, Czechia

Location

502

Prague, Czechia

Location

505

Terezín, Czechia

Location

503

Zlín, Czechia

Location

206

Montpellier, France

Location

204

Paris, France

Location

202

Tours, France

Location

252

Bad Nauheim, Germany

Location

257

Berlin, Germany

Location

258

Berlin, Germany

Location

262

Frankfurt, Germany

Location

255

Freiburg im Breisgau, Germany

Location

254

Hamburg, Germany

Location

253

Leipzig, Germany

Location

263

München, Germany

Location

256

Ratingen, Germany

Location

303

Budapest, Hungary

Location

304

Budapest, Hungary

Location

302

Debrecen, Hungary

Location

301

Gyula, Hungary

Location

306

Miskolc, Hungary

Location

300

Veszprém, Hungary

Location

100

Dublin, Ireland

Location

352

Ancona, Italy

Location

350

Pisa, Italy

Location

802

Cuernavaca, Mexico

Location

803

Mexico City, Mexico

Location

458

Bialystok, Poland

Location

452

Dąbrówka, Poland

Location

455

Elblag, Poland

Location

459

Gdansk, Poland

Location

457

Krakow, Poland

Location

450

Lublin, Poland

Location

454

Poznan, Poland

Location

453

Torun, Poland

Location

456

Warsaw, Poland

Location

462

Warsaw, Poland

Location

555

Madrid, Spain

Location

550

Mérida, Spain

Location

552

Santiago de Compostela, Spain

Location

553

Seville, Spain

Location

605

Barnsley, United Kingdom

Location

602

London, United Kingdom

Location

601

Salford, United Kingdom

Location

Related Publications (8)

• Mease PJ, Fleischmann R, Deodhar AA, Wollenhaupt J, Khraishi M, Kielar D, Woltering F, Stach C, Hoepken B, Arledge T, van der Heijde D. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014 Jan;73(1):48-55. doi: 10.1136/annrheumdis-2013-203696. Epub 2013 Aug 13.

  PMID: 23942868 RESULT

• van der Heijde D, Fleischmann R, Wollenhaupt J, Deodhar A, Kielar D, Woltering F, Stach C, Hoepken B, Arledge T, Mease PJ. Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis: results of the RAPID-PsA 24-week phase III double-blind randomised placebo-controlled study of certolizumab pegol. Ann Rheum Dis. 2014 Jan;73(1):233-7. doi: 10.1136/annrheumdis-2013-203697. Epub 2013 Aug 13.

  PMID: 23942869 RESULT

• van der Heijde D, Deodhar A, FitzGerald O, Fleischmann R, Gladman D, Gottlieb AB, Hoepken B, Bauer L, Irvin-Sellers O, Khraishi M, Peterson L, Turkiewicz A, Wollenhaupt J, Mease PJ. 4-year results from the RAPID-PsA phase 3 randomised placebo-controlled trial of certolizumab pegol in psoriatic arthritis. RMD Open. 2018 Mar 14;4(1):e000582. doi: 10.1136/rmdopen-2017-000582. eCollection 2018.

  PMID: 29556416 RESULT

• Walsh JA, Gottlieb AB, Hoepken B, Nurminen T, Mease PJ. Efficacy of certolizumab pegol with and without concomitant use of disease-modifying anti-rheumatic drugs over 4 years in psoriatic arthritis patients: results from the RAPID-PsA randomized controlled trial. Clin Rheumatol. 2018 Dec;37(12):3285-3296. doi: 10.1007/s10067-018-4227-7. Epub 2018 Sep 6.

  PMID: 30191421 DERIVED

• van der Heijde D, Deodhar A, Fleischmann R, Mease PJ, Rudwaleit M, Nurminen T, Davies O. Early Disease Activity or Clinical Response as Predictors of Long-Term Outcomes With Certolizumab Pegol in Axial Spondyloarthritis or Psoriatic Arthritis. Arthritis Care Res (Hoboken). 2017 Jul;69(7):1030-1039. doi: 10.1002/acr.23092. Epub 2017 Jun 2.

  PMID: 27696727 DERIVED

• Osterhaus JT, Purcaru O. Discriminant validity, responsiveness and reliability of the arthritis-specific Work Productivity Survey assessing workplace and household productivity in patients with psoriatic arthritis. Arthritis Res Ther. 2014 Jul 4;16(4):R140. doi: 10.1186/ar4602.

  PMID: 24996416 DERIVED

• Kavanaugh A, Gladman D, van der Heijde D, Purcaru O, Mease P. Improvements in productivity at paid work and within the household, and increased participation in daily activities after 24 weeks of certolizumab pegol treatment of patients with psoriatic arthritis: results of a phase 3 double-blind randomised placebo-controlled study. Ann Rheum Dis. 2015 Jan;74(1):44-51. doi: 10.1136/annrheumdis-2014-205198. Epub 2014 Jun 18.

  PMID: 24942382 DERIVED

• Gladman D, Fleischmann R, Coteur G, Woltering F, Mease PJ. Effect of certolizumab pegol on multiple facets of psoriatic arthritis as reported by patients: 24-week patient-reported outcome results of a phase III, multicenter study. Arthritis Care Res (Hoboken). 2014 Jul;66(7):1085-92. doi: 10.1002/acr.22256.

  PMID: 24339179 DERIVED

Related Links

• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Arthritis, Psoriatic

Interventions

Certolizumab Pegol

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: UCB
• Organization: Cares

+1877 822

Study Officials

• UCB Clinical Trial Call Center

  +1 877 822 9493 UCB

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 15, 2010
• First Posted: March 16, 2010
• Study Start: March 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: August 1, 2015
• Last Updated: August 1, 2018
• Results First Posted: February 25, 2014

Record last verified: 2017-01

Locations

AR (8); BE (2); IE (1); DE (9); ES (4); IT (2); US (27); BR (4); HU (6); CA (5); FR (3); GB (3); ME (2); PL (10); CZ (6)