A Study of the Safety and Effectiveness of Lyophilized Certolizumab Pegol in the Treatment of Signs and Symptoms of Rheumatoid Arthritis and in Prevention of Joint Damage in Patients With Active Rheumatoid Arthritis

Study Overview
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Brief Summary
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An open ended study in which patients who completed the double-blind study CDP870-027 [NCT00152386] are given Certolizumab Pegol (CZP) and assessed for signs and symptoms of Rheumatoid Arthritis (RA).

Official Title
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A Phase III Multi-centre, Open-label, follow-on Study to CDP870-027, to Assess the Efficacy and Safety of Lyophilized CDP870 an Engineered Human Anti-TNF PEG Conjugate, as Additional Medication to Methotrexate, in the Treatment of Signs and Symptoms and Preventing Structural Damage in Patients With Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: Certolizumab Pegol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have either failed to achieve American College of Rheumatology 20 % Response Criteria (ACR20) at Weeks 12 and 14 in C87027 [NCT00152386], or must have completed the entire Week 52 assessment of C87027 [NCT00152386] trial. Exclusion Criteria: A diagnosis of any other inflammatory Arthritis (e.g. Psoriatic Arthritis or Ankylosing Spondylitis) A secondary, non-inflammatory type of Arthritis (e.g. Osteoarthritis or Fibromyalgia) that in the Investigator's opinion is symptomatic enough to interfere with evaluation of the effect of CDP870 on the patient's primary diagnosis of Rheumatoid Arthritis Any concomitant biological therapy Any experimental therapy, within or outside a clinical trial

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Certolizumab Pegol<br>All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. | Biological: Certolizumab Pegol<br>* Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.<br>* Other names: Cimzia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With at Least One Adverse Event (AE) From First Certolizumab Pegol (CZP) Dose up to Approximately 7 Years | An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. First dose of Certolizumab Pegol (CZP) was at Baseline of the preceding double-blind study [NCT00152386] for subjects randomized to CZP, or at Entry Visit (Week 0) of this study for subjects randomized to Placebo. | From first dose of CZP to the end of the open-label study (approximately 7 years) | 
| Percentage of Subjects With at Least One Serious Adverse Event (SAE) From First Certolizumab Pegol (CZP) Dose up to Approximately 7 Years | A SAE is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalisation or prolongation of existing hospitalisation Results in persistent or significant disability/incapacity, or Is a congenital anomaly or birth defect Is as infection that requires treatment parenteral antibiotics Other important medical events which based on medical or scientific judgement may jeopardise the patients, or may require medical or surgical intervention to prevent any of the above First dose of CZP was at Baseline of the preceding double-blind study [NCT00152386] for subjects randomized to CZP, or at Entry Visit (Week 0) of this study for subjects randomized to Placebo. | From first dose of CZP to the end of the open-label study (approximately 7 years) | 
| Percentage of Subjects Who Withdrew Due to an Adverse Event (AE) During the Study | An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. The results of this Primary Outcome Measure are summarized from the Adverse Event pages of the Case Report Forms. | From Entry Visit (Week 0) to the end of the study (approximately 6.5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 48 | The assessments are based on a 20 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 48 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 96 | The assessments are based on a 20 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 96 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 144 | The assessments are based on a 20 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 144 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 192 | The assessments are based on a 20 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 192 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 240 | The assessments are based on a 20 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 240 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Completion/Withdrawal | The assessments are based on a 20 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years) | 
| Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 48 | The assessments are based on a 50 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 48 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 96 | The assessments are based on a 50 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 96 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 144 | The assessments are based on a 50 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 144 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 192 | The assessments are based on a 50 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 192 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 240 | The assessments are based on a 50 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 240 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Completion/Withdrawal | The assessments are based on a 50 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years) | 
| Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 48 | The assessments are based on a 70 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 48 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 96 | The assessments are based on a 70 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 96 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 144 | The assessments are based on a 70 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 144 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 192 | The assessments are based on a 70 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 192 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 240 | The assessments are based on a 70 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Week 240 of the open-label study | 
| Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Completion/Withdrawal | The assessments are based on a 70 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study. | From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years) | 
| Change From Baseline of the Preceding Double-Blind Study to Week 96 in Modified Total Sharp Score (mTSS) | The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively, as assessed by x-rays of the hands and feet. The score ranges from 0 to 448 with higher scores representing greater damage. A negative value in mTSS change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement. | From Baseline of the preceding double-blind study to Week 96 of the open-label study | 
| Change From Baseline of the Preceding Double-Blind Study to Completion/Withdrawal Visit in Health Assessment Questionnaire - Disability Index (HAQ-DI) Total Score | The HAQ-DI assesses the degree of difficulty experienced in eight domains (Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Gripping, Other Activities) of daily living activities using 20 questions. The HAQ-DI is calculated by summing the domain scores and dividing them by the number of domains. It ranges from 0 (no difficulty) to 3 (unable to do). Negative values indicate an improvement from Baseline to the Post-Baseline Visit with larger negative values showing a better improvement. | From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years) | 
| Change From Baseline to Completion/Withdrawal Visit in Duration of Morning Stiffness | Morning stiffness is defined as the time in hours elapsed between the time of usual awakening (even if not in the morning) and the time the subject is as limber as he/she will be during a day involving typical activities. A negative value in duration of morning stiffness change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement. | From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years) | 
| Change From Baseline to Completion/Withdrawal Visit in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28[ESR]) | 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 (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. A negative value in DAS28[ESR] change from Baseline indicates an improvement from Baseline. | From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years) | 
| Percentage of Subjects With Good European League Against Rheumatism (EULAR) Response at Completion/Withdrawal Visit | Good EULAR response is defined as Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28[ESR]) improvement from Baseline of the preceding double-blind study > 1.2 and DAS28[ESR] value < 3.2. | From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years) | 
| Change From Baseline to Completion/Withdrawal Visit in Short-Form Health Survey (SF-36) Item Questionnaire Physical Component Summary (PCS) Score | The SF-36 is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept PCS score are scored to yield values between 0 (worst) and 100 (best). | From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years) | 
| Change From Baseline to Completion/Withdrawal Visit in Short-Form Health Survey (SF-36) Item Questionnaire Mental Component Summary (MCS) Score | The SF-36 is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept MCS score are scored to yield values between 0 (worst) and 100 (best). | From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, CDP870, Certolizumab Pegol, Cimzia