Rheumatoid Arthritis (RA) Moderate to Low Disease Activity Study (CERTAIN)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB, Inc.
ClinicalTrials.gov Identifier:
NCT00674362
First received: May 5, 2008
Last updated: December 9, 2011
Last verified: December 2011
  Purpose

To assess the clinical efficacy and safety of certolizumab pegol as add-on therapy with stable-dose disease-modifying antirheumatic drugs (DMARDs) for achieving clinical remission in patients with moderate to low disease activity rheumatoid arthritis


Condition Intervention Phase
Rheumatoid Arthritis
Biological: Certolizumab pegol
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IIIB, Multi-center, Double-blind, Placebo-controlled, Parallel Group, 52-week Study to Evaluate the Safety and Efficacy of Certolizumab Pegol, Administered With DMARDs, in Patients With Low to Moderate Disease Activity Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by UCB, Inc.:

Primary Outcome Measures:
  • Clinical Disease Activity Index (CDAI) Remission (≤2.8) at Both Week 20 and Week 24 [ Time Frame: Week 20 and Week 24 ] [ Designated as safety issue: No ]
    CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI)


Secondary Outcome Measures:
  • 28-joint Count Disease Activity Score (DAS28-ESR) Remission (<2.6) at Both Week 20 and Week 24 [ Time Frame: Week 20 and Week 24 ] [ Designated as safety issue: No ]
    DAS28-ESR is calculated using the tender joint count (TJC), swollen joint count (SJC) erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Patient Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI)

  • Simplified Disease Activity Index (SDAI) Remission (≤3.3) at Both Week 20 and Week 24 [ Time Frame: Week 20 and Week 24 ] [ Designated as safety issue: No ]
    SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI)

  • Time From Stopping Treatment (Week 24) to Loss of Remission (up to Week 52) Assessed Using Clinical Disease Activity Index (CDAI) Scores at 2 Consecutive Visits [ Time Frame: Week 24 up to Week 52 ] [ Designated as safety issue: No ]
    CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Patients losing remission (CDAI >2.8) for two consecutive visits will be considered as having the event on the day of the visit where remission was first lost. Subjects discontinued/non-remitted by Week 24 are considered as having the event on day 1.

  • Time From Stopping Treatment (Week 24) to Loss of Remission (up to Week 52) Assessed Using Simplified Disease Activity Index (SDAI) Scores at 2 Consecutive Visits [ Time Frame: Week 24 up to Week 52 ] [ Designated as safety issue: No ]
    SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (mg/dL), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in cm) and Physician's Global Assessment of Disease Activity (PhGADA-VAS in cm). 28 joints are examined. A lower score indicates less disease activity. Patients losing remission (SDAI >3.3) for two consecutive visits will be considered as having the event on the day of the visit where remission was first lost. Subjects discontinued/non-remitted by Week 24 are considered as having the event on day 1.

  • Time From Stopping Treatment (Week 24) to Loss of Remission (up to Week 52) Assessed Using DAS28-ESR Scores at 2 Consecutive Visits [ Time Frame: Week 24 up to Week 52 ] [ Designated as safety issue: No ]
    DAS28-ESR is calculated using tender joint count (TJC), swollen joint count (SJC), erythrocyte sedimentation rate (ESR mm/hour) and Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS mm). 0.56x√(TJC) + 0.28x√(SJC) + 0.70xlognat(ESR) + 0.014xPtGADA-VAS. 28 joints are examined. Lower score indicates less disease activity. Patients losing remission (DAS28-ESR≥2.6) for two consecutive visits will be considered as having the event on the first of the two visits. Subjects discontinued/non-remitted by Week 24 are considered as having the event on day 1.

  • American College of Rheumatology 20% (ACR20) Response at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)

  • American College of Rheumatology 50% (ACR50) Response at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    ACR50 responders are subjects with at least 50% 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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)

  • American College of Rheumatology 70% (ACR70) Response at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    ACR70 responders are subjects with at least 70% 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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)

  • Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Change from Baseline is computed as the value at Week 24 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

  • Change From Baseline in Short Form 36-items Health Survey (SF-36) Physical Component Summary (PCS) Scores at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    PCS norm-based scores are calculated based upon the following 8 domain scores, Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, and range from 1 to 81, where 50 represents the normative value. A larger positive value in change from Baseline indicates an improvement.

  • Change From Baseline in Short Form 36-items Health Survey (SF-36) Mental Component Summary (MCS) Scores at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    MCS norm-based scores are calculated based upon the following 8 domain scores, Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, and range from -9 to 82, where 50 represents the normative value. A larger positive value in change from Baseline indicates an improvement

  • Change From Baseline in Short Form 36-items Health Survey (SF-36) Physical Functioning Domain at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement

  • Change From Baseline in Short Form 36-items Health Survey (SF-36) Role Physical Domain at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement

  • Change From Baseline in Short Form 36-items Health Survey (SF-36) Bodily Pain Domain at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement

  • Change From Baseline in Short Form 36-items Health Survey (SF-36) General Health Domain at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement

  • Change From Baseline in Short Form 36-items Health Survey (SF-36) Vitality Domain at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement

  • Change From Baseline in Short Form 36-items Health Survey (SF-36) Social Functioning Domain at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement

  • Change From Baseline in Short Form 36-items Health Survey (SF-36) Role Emotional Domain at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement

  • Change From Baseline in Short Form 36-items Health Survey (SF-36) Mental Health Domain at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement

  • Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (VAS) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Change from Baseline in Patient's Assessment of Arthritis Pain-VAS (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) is computed as the value at Week 24 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

  • Change From Baseline in Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Change from Baseline in Patient's Global Assessment of Disease Activity-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 24 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

  • Change From Baseline in Fatigue Assessment Scale at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Change from Baseline in Fatigue Assessment scale (0 to 10, 0 is "No Fatigue" and 10 is "Fatigue as bad as you can imagine") is computed as the value at Week 24 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.


Enrollment: 194
Study Start Date: June 2008
Study Completion Date: December 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Certolizumab pegol 200 mg (CDP870)
Two 200 mg subcutaneous injections at Week 0, Week 2, and Week 4 followed by 200 mg injections every 2 weeks until the last drug administration (Week 22)
Biological: Certolizumab pegol
Two 200 mg subcutaneous injections at Week 0, Week 2, and Week 4 followed by 200 mg injections every 2 weeks until the last drug administration (Week 22)
Other Names:
  • CDP870
  • Cimzia
Placebo Comparator: Placebo
Two 0.9% saline subcutaneous injections at Week 0, Week 2, and Week 4 followed by 0.9% saline injections every 2 weeks until the last drug administration (Week 22)
Biological: Placebo
Two 0.9% saline subcutaneous injections at Week 0, Week 2, and Week 4 followed by 0.9% saline injections every 2 weeks until the last drug administration (Week 22)

Detailed Description:

Treatment period starts with a 24-week, double blind, placebo-controlled, randomized period followed by an open label phase until week 52.

In the double blind phase eligible patients will be randomized via an Interactive Voice Response System (IVRS) in a 1:1 ratio to receive either certolizumab pegol (400 mg at Weeks 0, 2 and 4, followed by 200 mg every two weeks) or placebo up to and including Week 22. All patients will continue to receive their Disease Modifying AntiRheumatic Drugs (DMARDs) therapy established before study entry until Week 52. At Week 24, patients will not receive any injection but will be evaluated:

  • Non-remitters at Week 24 (patients who did not achieve remission at both Week 20 and Week 24) will be discontinued from the study and may be given the opportunity to enter in an open-label follow-up trial, C87080 [NCT00843778], with certolizumab pegol.
  • Remitters (i.e. patients who achieved remission as measured by Clinical Disease Activity Index (CDAI) at both Week 20 and Week 24) will stop their randomized treatment (certolizumab pegol or placebo) and be followed up until Week 52. Remitters who flare up (CDAI ≥11 confirmed at two consecutive visits four weeks apart) between Week 24 and Week 52 will be re-treated with the same dosing regimen of certolizumab pegol (3 administrations of 400mg, given every 2 weeks, followed by 200 mg given every other week) up to and including Week 50.

Remitters who flare up between Week 24 and Week 52 and complete 52-week study period will be allowed to enter open label follow up trial at Week 52.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with established diagnosis of low to moderate adult rheumatoid arthritis, currently on Disease Modifying AntiRheumatic Drugs (DMARDs) therapy for at least six months and not longer than 10 years

Exclusion Criteria:

  • All the concomitant diseases or pathological conditions that could interfere and impact the assessment of the study treatment, or with the safety of the patient
  • Previous clinical trials and previous biological therapy that could interfere with the results in the present clinical trial
  • Patients must not have received any previous biological therapy for rheumatoid arthritis (RA)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00674362

Locations
Austria
Graz, Austria
Wien, Austria
France
Nantes, France
Paris, France
Rennes, France
Rouen, France
Tours, France
Germany
Bad Nauheim, Germany
Berlin, Germany
Erlangen, Germany
Essen, Germany
Frankfurt, Germany
Hamburg, Germany
Heidelberg, Germany
Herne, Germany
Ratingen, Germany
Vogelsang-Gom, Germany
Wurzburg, Germany
Italy
Ferrara, Italy
Padova, Italy
Pavia, Italy
Roma, Italy
Poland
Bialystok, Poland
Bydgoszcz, Poland
Elblag, Poland
Lublin, Poland
Poznan, Poland
Sopot, Poland
Szczecin, Poland
Torun, Poland
Wroclaw, Poland
Sponsors and Collaborators
UCB, Inc.
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

Additional Information:
No publications provided

Responsible Party: UCB, Inc.
ClinicalTrials.gov Identifier: NCT00674362     History of Changes
Other Study ID Numbers: C87076, 2007-000828-40
Study First Received: May 5, 2008
Results First Received: December 9, 2011
Last Updated: December 9, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Austria: Agency for Health and Food Safety
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by UCB, Inc.:
Rheumatoid Arthritis
Moderate to Low Disease activity
Certolizumab pegol

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Immunoglobulin Fab Fragments
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014