Rheumatoid Arthritis (RA) Moderate to Low Disease Activity Study

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: Certolizumab pegol
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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)

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Certolizumab pegol 200 mg (CDP870)<br>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<br>* 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)<br>* Other names: Cimzia;|
| Placebo Comparator: Placebo<br>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<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Disease Activity Index (CDAI) Remission (≤2.8) at Both Week 20 and Week 24 | 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) | Week 20 and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-joint Count Disease Activity Score (DAS28-ESR) Remission (<2.6) at Both Week 20 and Week 24 | 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) | Week 20 and Week 24 | 
| Simplified Disease Activity Index (SDAI) Remission (≤3.3) at Both Week 20 and Week 24 | 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) | Week 20 and Week 24 | 
| 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 | 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. | Week 24 up to Week 52 | 
| 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 | 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. | Week 24 up to Week 52 | 
| Time From Stopping Treatment (Week 24) to Loss of Remission (up to Week 52) Assessed Using DAS28-ESR Scores at 2 Consecutive Visits | 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. | Week 24 up to Week 52 | 
| American College of Rheumatology 20% (ACR20) Response at Week 24 | 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) | Baseline, Week 24 | 
| American College of Rheumatology 50% (ACR50) Response at Week 24 | 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) | Baseline, Week 24 | 
| American College of Rheumatology 70% (ACR70) Response at Week 24 | 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) | Baseline, Week 24 | 
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 | 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. | Baseline, Week 24 | 
| Change From Baseline in Short Form 36-items Health Survey (SF-36) Physical Component Summary (PCS) Scores at Week 24 | 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. | Baseline, Week 24 | 
| Change From Baseline in Short Form 36-items Health Survey (SF-36) Mental Component Summary (MCS) Scores at Week 24 | 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 | Baseline, Week 24 | 
| Change From Baseline in Short Form 36-items Health Survey (SF-36) Physical Functioning Domain at Week 24 | 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 | Baseline, Week 24 | 
| Change From Baseline in Short Form 36-items Health Survey (SF-36) Role Physical Domain at Week 24 | 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 | Baseline, Week 24 | 
| Change From Baseline in Short Form 36-items Health Survey (SF-36) Bodily Pain Domain at Week 24 | 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 | Baseline, Week 24 | 
| Change From Baseline in Short Form 36-items Health Survey (SF-36) General Health Domain at Week 24 | 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 | Baseline, Week 24 | 
| Change From Baseline in Short Form 36-items Health Survey (SF-36) Vitality Domain at Week 24 | 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 | Baseline, Week 24 | 
| Change From Baseline in Short Form 36-items Health Survey (SF-36) Social Functioning Domain at Week 24 | 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 | Baseline, Week 24 | 
| Change From Baseline in Short Form 36-items Health Survey (SF-36) Role Emotional Domain at Week 24 | 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 | Baseline, Week 24 | 
| Change From Baseline in Short Form 36-items Health Survey (SF-36) Mental Health Domain at Week 24 | 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 | Baseline, Week 24 | 
| Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (VAS) at Week 24 | 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. | Baseline, Week 24 | 
| Change From Baseline in Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS) at Week 24 | 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. | Baseline, Week 24 | 
| Change From Baseline in Fatigue Assessment Scale at Week 24 | 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. | Baseline, Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Moderate to Low Disease activity, Certolizumab pegol