Can TNF-Alpha Incomplete Secondary Responders Attain a Safe and Efficacious Response Switching to Cimzia

Rheumatoid Arthritis Clinical Trial

Official title:

Can TNF-Alpha Incomplete Secondary Responders Attain a Safe and Efficacious Response By Switching to Certolizumab Pegol (Cimzia)? A Phase IV, Randomized, Multi-Center, Double-Blind, Twelve-Week Study Followed by a 12-Week Open-Label Phase

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01147341
• Other study ID #: CERT-001
• Status: Completed
• Phase: Phase 4
• First received: June 17, 2010
• Last updated: May 29, 2014
• Start date: July 2010
• Est. completion date: January 2012

Study information

• Verified date: May 2014
• Source: Schiff, Michael, M.D.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Purpose of the study is to determine if Cimzia is safe and effective in subjects who have received previous treatment with a TNF-alpha inhibitor other than Cimzia.

Description:

This is a Phase IV, randomized, multi-center, double-blind, parallel-group 12-week study of Cimzia with concomitant methotrexate (MTX) or other DMARD compared to MTX or other DMARD alone in patients with an inadequate secondary therapeutic response to a TNF-alpha inhibitor as defined above and active rheumatoid arthritis (RA) followed by a 12-week open-label phase with concomitant MTX or other DMARD and Cimzia.

Subjects must washout from the previous TNF inhibitor for at least 4 weeks prior to the baseline visit. Subjects unable to tolerate MTX must have been on a stable dose of another non-biologic DMARD for at least 3 months. Subjects' diagnosis of RA must be based on the 1987 Revised American Rheumatism Association Criteria for the Classification of Rheumatoid Arthritis.

Subjects will be screened for eligibility and, up to 28 days later, at the baseline visit, randomized to one of two treatment groups (2:1): Cimzia or placebo (in addition to concomitant MTX or other DMARD). All subjects will continue MTX/other DMARD at the same dose utilized prior to study entry.

After the Week 12 study visit, all subjects will have the opportunity to continue in the study on open-label Cimzia treatment (using an induction regimen for all subjects, regardless of their treatment in the blinded phase).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Have a diagnosis of RA at least 6 months

• Have received treatment with a TNF-alpha inhibitor

• Be receiving Methotrexate (with folic acid)at a dose of at least 10mg/week or another non-biologic DMARD if Methotrexate intolerant *Have at least 6 tender joint and 6 swollen joints*

• Have an CRP greater than or equal to ULN

• Availability of a chest x-ray that shows no evidence of active TB or infection

Exclusion Criteria:

• Prior exposure to Cimzia

• Prior treatment with B-cell depleting therapy

• No significant response to previous TNF inhibitor

• Congestive heart failure

• Clinically abnormal laboratory tests

• History of cancer

• Active TB

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Cimzia
prefilled 200mg Cimzia syringe SC q 2 weeks
• Placebo
prefilled saline syringe

Locations

Country	Name	City	State
United States	Mountain State Clinical Research	Clarksburg	West Virginia
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Rheumatology Associates of N. Alabama	Huntsville	Alabama
United States	Physician Research Collaboration, LLC	Lincoln	Nebraska
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Rheumatology and Immunotherapy Center	Oak Creek	Wisconsin
United States	Westroads Medical Group	Omaha	Nebraska
United States	Buffalo Rheumatology	Orchard Park	New York
United States	Sun Valley Arthritis Center, Ltd.	Peoria	Arizona
United States	Arizona Arthritis and Rhematolgy Research	Phoenix	Arizona
United States	Sarasota Arthritis Research Center	Sarasota	Florida
United States	Rheumatology Associates of Long Island	Smithtown	New York

Sponsors (2)

Lead Sponsor	Collaborator
Michael Schiff, MD	UCB Pharma

Country where clinical trial is conducted

United States, 

References & Publications (1)

Schiff MH, von Kempis J, Goldblum R, Tesser JR, Mueller RB. Rheumatoid arthritis secondary non-responders to TNF can attain an efficacious and safe response by switching to certolizumab pegol: a phase IV, randomised, multicentre, double-blind, 12-week stu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of Subjects Achieving a CDAI Decrease of Greater Than or Equal to 10 Points in the Cimzia Treatment Group Compared to the Placebo Group at Week 24	The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI = 2.8; Low Disease Activity: CDAI > 2.8 and = 10 ;Moderate Disease Activity: CDAI > 10 and = 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement.	Baseline to Week 24	No
Other	Proportion of Subjects Achieving an American College of Rheumatology 20% (ACR20) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group	ACR20 responders are subjects with at least 20% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale.; HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do.; Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.	Baseline to Week 24	No
Other	Proportion of Subjects Achieving an American College of Rheumatology 50% (ACR50) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group	ACR50 responders are subjects with at least 50% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale.; HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do.; Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.	Baseline to Week 24	No
Other	Proportion of Subjects Achieving an American College of Rheuamtology Low Disease Activity Score and/or Remission Score in the Cimzia Group Compared to the Placebo Group as Calculated by DAS28 (CRP)	The Disease Activity Score-28-C-reactive Protein (DAS28-CRP)is a composite measure for rheumatoid arthritis (RA) is based on 4 variables: tender and swollen joint counts (28 joints),C-Reactive Protein(CRP), and patient global assessment visual analog scale. A lower score indicated less disease activity.; Remission: CDAI = 2.8; Low Disease Activity: CDAI > 2.8 and = 10 ;Moderate Disease Activity: CDAI > 10 and = 22; High Disease Activity: CDAI > 22	Baseline to Week 24	No
Other	Proportion of Subjects Achieving a EULAR Good or Moderate Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group	The EULAR (European League Against Rheumatism) response criteria is a classified response criteria which classifies the patients individual as non-, moderate or good responders dependent on the change and the level of the Disease Activity Score.; The Disease Activity Score(DAS28) is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from baseline), or no response (absolute: >5.1 or <0.6 change from baseline).	Baseline to Week 24	No
Other	Proportion of Subjects Achieving a CDAI Score Decrease Greater Than or Equal to 13.9 Points in the CimZia Treatment Group Compared to the Placebo Group at Week 24	The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity) Remission: CDAI = 2.8; Low Disease Activity: CDAI > 2.8 and = 10 ;Moderate Disease Activity: CDAI > 10 and = 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement.	Baseline to Week 24	No
Primary	Proportion of Subjects Achieving a Clinical Disease Activity Index (CDAI) Decrease of Greater Than or Equal to 10 Points in the Cimzia Treatment Group Compared to the Placebo Group at Week 12	The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI = 2.8; Low Disease Activity: CDAI > 2.8 and = 10 ;Moderate Disease Activity: CDAI > 10 and = 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement.	Baseline to week 12	No
Primary	Proportion of Subjects Achieving an American College of Rheumatology 20% (ACR20) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group	ACR20 responders are 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 (VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale(VAS).; HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do.; Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.	From Baseline to Week 12	No
Secondary	Proportion of Subjects Achieving an American College of Rheumatology 50% (ACR50) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group at Week 12	ACR50 responders are subjects with at least 50% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale.; HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do.; Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.	Baseline to Week 12	No
Secondary	Proportion of Subjects Achieving an American College of Rheuamtology Low Disease Activity Score and/or Remission Score in the Cimzia Group Compared to the Placebo Group as Calculated by DAS28 (CRP)	The Disease Activity Score-28-C-reactive Protein (DAS28-CRP)is a composite measure for rheumatoid arthritis (RA) is based on 4 variables: tender and swollen joint counts (28 joints),C-Reactive Protein(CRP), and patient global assessment visual analog scale. A lower score indicated less disease activity.; Remission: CDAI = 2.8; Low Disease Activity: CDAI > 2.8 and = 10 ;Moderate Disease Activity: CDAI > 10 and = 22; High Disease Activity: CDAI > 22	Baseline to Week 12	No
Secondary	Proportion of Subjects Achieving a EULAR Good or Moderate Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group	The EULAR (European League Against Rheumatism) response criteria is a classified response criteria which classifies the patients individual as non-, moderate or good responders dependent on the change and the level of the Disease Activity Score.; The Disease Activity Score(DAS28) is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from baseline), or no response (absolute: >5.1 or <0.6 change from baseline).	Baseline to week 12	No
Secondary	Proportion of Subjects Achieving a CDAI Score Decrease Greater Than or Equal to 13.9 Points in the CimZia Treatment Group Compared to the Placebo Group at Week 12	The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI = 2.8; Low Disease Activity: CDAI > 2.8 and = 10 ;Moderate Disease Activity: CDAI > 10 and = 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement..	Baseline to week 12	No

External Links

•   EULAR 2012 SAT0144
•   Schiff,m