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

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ClinicalTrials.gov Identifier: NCT01147341
Recruitment Status : Completed
First Posted : June 22, 2010
Results First Posted : March 26, 2014
Last Update Posted : June 9, 2014
Sponsor:
Collaborator:
UCB Pharma
Information provided by (Responsible Party):
Michael Schiff, MD, Schiff, Michael, M.D.

Brief 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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Cimzia Drug: Placebo Phase 4

Detailed 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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Study Start Date : July 2010
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arthritis

Arm Intervention/treatment
Placebo Comparator: placebo
Placebo (0.9% sodium chloride) given as 2 subcutaneous (sc) injections at weeks 0, 2, and 4, followed y 1 sc injection given an weeks 6, 8, and 10. At week 12 subjects entered the open label phase. Subjects received 400 mg of Cimzia (CZP) given as two 200 mg subcutaneous (sc) injections at weeks 12,14 and 16, followed by 1 sc injection at weeks 18, 20, and 22.
Drug: Placebo
prefilled saline syringe
Other Name: 1 ml Sodium Cloride 0.9%

Active Comparator: active treatment with Cimzia
400 mg of Cimzia (CZP) given as two 200 mg subcutaneous (sc) injections at weeks 0, 2, and 4, followed by 1 sc injection at weeks 6, 8, and 10. At week 12 subjects entered the open label phase. Subjects received 400 mg of Cimzia (CZP) given as two 200 mg subcutaneous (sc) injections at weeks 12,14 and 16, followed by 1 sc injection at weeks 18, 20, and 22.
Drug: Cimzia
prefilled 200mg Cimzia syringe SC q 2 weeks
Other Name: 1 ml liquid product containing 200mg of Certolizumab Pegol




Primary Outcome Measures :
  1. 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 [ Time Frame: Baseline to 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.

  2. Proportion of Subjects Achieving an American College of Rheumatology 20% (ACR20) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group [ Time Frame: From Baseline to Week 12 ]

    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.



Secondary Outcome Measures :
  1. 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 [ Time Frame: Baseline to 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.


  2. 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) [ Time Frame: Baseline to Week 12 ]

    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


  3. Proportion of Subjects Achieving a EULAR Good or Moderate Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group [ Time Frame: Baseline to week 12 ]

    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).


  4. 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 [ Time Frame: Baseline to 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..


Other Outcome Measures:
  1. 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 [ Time Frame: Baseline to 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.

  2. Proportion of Subjects Achieving an American College of Rheumatology 20% (ACR20) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group [ Time Frame: Baseline to Week 24 ]

    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.


  3. Proportion of Subjects Achieving an American College of Rheumatology 50% (ACR50) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group [ Time Frame: Baseline to Week 24 ]

    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.


  4. 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) [ Time Frame: Baseline to Week 24 ]

    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


  5. Proportion of Subjects Achieving a EULAR Good or Moderate Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group [ Time Frame: Baseline to Week 24 ]

    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).


  6. 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 [ Time Frame: Baseline to 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.



Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01147341


Locations
Layout table for location information
United States, Alabama
Rheumatology Associates of N. Alabama
Huntsville, Alabama, United States, 35801
United States, Arizona
Sun Valley Arthritis Center, Ltd.
Peoria, Arizona, United States, 85381
Arizona Arthritis and Rhematolgy Research
Phoenix, Arizona, United States, 85037
United States, Florida
Sarasota Arthritis Research Center
Sarasota, Florida, United States, 34239
United States, Nebraska
Physician Research Collaboration, LLC
Lincoln, Nebraska, United States, 68516
Westroads Medical Group
Omaha, Nebraska, United States, 68114
United States, New Jersey
Morristown Memorial Hospital
Morristown, New Jersey, United States, 07960
United States, New York
Buffalo Rheumatology
Orchard Park, New York, United States, 14127
Rheumatology Associates of Long Island
Smithtown, New York, United States, 11787
United States, Pennsylvania
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
United States, West Virginia
Mountain State Clinical Research
Clarksburg, West Virginia, United States, 26301
United States, Wisconsin
Rheumatology and Immunotherapy Center
Oak Creek, Wisconsin, United States, 53154
Sponsors and Collaborators
Michael Schiff, MD
UCB Pharma
Investigators
Layout table for investigator information
Study Director: Michael H Schiff, MD
Additional Information:
Publications of Results:
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Responsible Party: Michael Schiff, MD, MD, Schiff, Michael, M.D.
ClinicalTrials.gov Identifier: NCT01147341    
Other Study ID Numbers: CERT-001
First Posted: June 22, 2010    Key Record Dates
Results First Posted: March 26, 2014
Last Update Posted: June 9, 2014
Last Verified: May 2014
Keywords provided by Michael Schiff, MD, Schiff, Michael, M.D.:
rheumatoid arthritis
anti-TNF therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Certolizumab Pegol
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents