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

Study Overview
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Brief Summary
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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).

Official Title
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Phase 3, Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Subjects With Adult-Onset Active and Progressive Psoriatic Arthritis (PsA)

Conditions
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Arthritis, Psoriatic

Intervention / Treatment
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* Biological: CZP 200 mg Q2W
* Biological: CZP 400 mg Q4W
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CZP 200 mg Q2W<br>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<br>* 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|
| Experimental: CZP 400 mg Q4W<br>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<br>* 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|
| Placebo Comparator: Placebo<br>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<br>* Matching Placebo to CZP injection.<br>|
| Other: Placebo to CZP 200 mg escape on Week 16<br>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<br>* 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|
| Other: Placebo to CZP 400 mg escape on Week 16<br>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<br>* 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|
| Other: Placebo to CZP 200 mg on Week 24<br>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<br>* 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|
| Other: Placebo to CZP 400 mg on Week 24<br>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<br>* 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American College of Rheumatology 20 (ACR20) Response at Week 24 | ACR20 responders are those subjects with at least 20 % improvement from Baseline 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 24 | 
| Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24 | The HAQ-DI is a measure of function in Arthritis. There are 20 items in eight categories that represent a comprehensive set of functional activities on a scale from 0 (without difficulty) to 3 (unable to perform without assistance). The category scores are averaged into an overall HAQ-DI from 0 to 3. Scores of 0 to 1 generally represent mild to moderate difficulty, 1 to 2 represent moderate to severe disability, and 2 to 3 indicate severe to very severe disability. A negative value in HAQ-DI change from Baseline indicates an improvement from Baseline. The higher the negative value, the higher the improvement. | 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 | The PASI75 response assessments are based on at least 75 % improvement in the PASI score from Baseline. The PASI score is a measure of the average redness, thickness, and scaliness of the psoriatic skin lesions (each graded on a 0 to 4 scale), weighted by the area of involvement. | Week 24 | 
| Change From Baseline in Modified Total Sharp Score (mTSS) at Week 48 | 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 analysis of this outcome measure, the change from Baseline to Week 48 was imputed using the median change from Baseline among all subjects for those subjects, which had less than 2 radiographs. The post-hoc analysis presented here is based on the subgroup of subjects which had a Baseline mTSS value greater than 6. | From Baseline to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Certolizumab Pegol, Cimzia