Certolizumab Pegol in Subjects With Adult Onset Active and Progressive Psoriatic Arthritis
- Conditions
- Arthritis, Psoriatic
- Interventions
- Biological: CZP 400 mg Q4WBiological: CZP 200 mg Q2WOther: Placebo
- Registration Number
- NCT01087788
- Lead Sponsor
- UCB BIOSCIENCES GmbH
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 409
-
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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CZP 200 mg Q2W Placebo 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. CZP 400 mg Q4W CZP 400 mg Q4W 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. Placebo to CZP 200 mg escape on Week 16 CZP 200 mg Q2W 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. Placebo to CZP 200 mg on Week 24 CZP 200 mg Q2W 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. CZP 200 mg Q2W CZP 200 mg Q2W 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. CZP 400 mg Q4W Placebo 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. Placebo Placebo 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). Placebo to CZP 400 mg on Week 24 CZP 400 mg Q4W 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. Placebo to CZP 400 mg escape on Week 16 CZP 400 mg Q4W 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. Placebo to CZP 200 mg on Week 24 Placebo 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. Placebo to CZP 400 mg on Week 24 Placebo 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. Placebo to CZP 200 mg escape on Week 16 Placebo 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. Placebo to CZP 400 mg escape on Week 16 Placebo 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Modified Total Sharp Score (mTSS) in Modification for Psoriatic Arthritis at Week 24 From Baseline to 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.
American College of Rheumatology 20 (ACR20) Response at Week 12 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).
- Secondary Outcome Measures
Name Time Method Change From Baseline in Modified Total Sharp Score (mTSS) at Week 48 From Baseline to 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.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 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.
American College of Rheumatology 20 (ACR20) Response at Week 24 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).
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24 From Baseline to 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.
Trial Locations
- Locations (92)
456
🇵🇱Warszawa, Poland
501
🇨🇿Hlucin, Czechia
761
🇧🇷Goiâna, Brazil
550
🇪🇸Mérida, Spain
951
🇺🇸Middleburg Heights, Ohio, United States
750
🇧🇷Curitiba, Brazil
905
🇨🇦Trois-Rivires, Quebec, Canada
303
🇭🇺Budapest, Hungary
454
🇵🇱Poznan, Poland
968
🇺🇸Seattle, Washington, United States
100
🇮🇪Dublin 4, Ireland
706
🇦🇷Rosario, Argentina
757
🇧🇷Goias, Brazil
300
🇭🇺Veszprém, Hungary
256
🇩🇪Ratingen, Germany
704
🇦🇷Buenos Aires, Argentina
710
🇦🇷San Juan, Argentina
350
🇮🇹Pisa, Italy
254
🇩🇪Hamburg, Germany
452
🇵🇱Dabrowka, Poland
910
🇨🇦Windsor, Ontario, Canada
450
🇵🇱Lublin, Poland
302
🇭🇺Debrecen, Hungary
504
🇨🇿Brno, Czechia
304
🇭🇺Budapest, Hungary
301
🇭🇺Gyula, Hungary
202
🇫🇷Tours, France
707
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
705
🇦🇷Cordoba, Argentina
505
🇨🇿Terezin, Czechia
152
🇧🇪Gent, Belgium
262
🇩🇪Frankfurt, Germany
204
🇫🇷Paris, France
257
🇩🇪Berlin, Germany
258
🇩🇪Berlin, Germany
702
🇦🇷San Miguel De Tucuman, Argentina
252
🇩🇪Bad Nauheim, Germany
151
🇧🇪Liege, Belgium
972
🇺🇸Duncansville, Pennsylvania, United States
555
🇪🇸Madrid, Spain
900
🇨🇦St. John's, Newfoundland and Labrador, Canada
206
🇫🇷Montpellier, France
500
🇨🇿Pardubice, Czechia
253
🇩🇪Leipzig, Germany
700
🇦🇷Buenos Aires, Argentina
753
🇧🇷Porto Alegre, Brazil
552
🇪🇸Santiago de Compostela, Spain
708
🇦🇷San Miguel de Tucuman, Argentina
502
🇨🇿Praha 2, Czechia
503
🇨🇿Zlin, Czechia
553
🇪🇸Sevilla, Spain
802
🇲🇽Cuernavaca, Mexico
458
🇵🇱Bialystok, Poland
352
🇮🇹Ancona, Italy
255
🇩🇪Freiburg, Germany
455
🇵🇱Elblag, Poland
459
🇵🇱Gdansk, Poland
457
🇵🇱Krakow, Poland
602
🇬🇧London, United Kingdom
601
🇬🇧Salford, United Kingdom
957
🇺🇸Aventura, Florida, United States
975
🇺🇸Dallas, Texas, United States
907
🇨🇦Victoria, British Columbia, Canada
904
🇨🇦Toronto, Ontario, Canada
462
🇵🇱Warszawa, Poland
953
🇺🇸Tuscaloosa, Alabama, United States
954
🇺🇸Peoria, Arizona, United States
971
🇺🇸Scottsdale, Arizona, United States
966
🇺🇸Palm Desert, California, United States
962
🇺🇸Fort Lauderdale, Florida, United States
959
🇺🇸Orange Park, Florida, United States
958
🇺🇸Vero Beach, Florida, United States
964
🇺🇸Hagerstown, Maryland, United States
960
🇺🇸Kalamazoo, Michigan, United States
969
🇺🇸Eagan, Minnesota, United States
965
🇺🇸Florissant, Missouri, United States
984
🇺🇸Flowood, Mississippi, United States
950
🇺🇸Saint Louis, Missouri, United States
985
🇺🇸Brooklyn, New York, United States
963
🇺🇸Asheville, North Carolina, United States
976
🇺🇸Cleveland, Ohio, United States
803
🇲🇽Mexico D.F., Mexico
978
🇺🇸Houston, Texas, United States
961
🇺🇸Birmingham, Alabama, United States
952
🇺🇸San Diego, California, United States
970
🇺🇸Oklahoma City, Oklahoma, United States
982
🇺🇸Portland, Oregon, United States
967
🇺🇸San Antonio, Texas, United States
263
🇩🇪München, Germany
306
🇭🇺Miskolc, Hungary
605
🇬🇧Barnsley, United Kingdom
453
🇵🇱Torun, Poland