Long-term Treatment Study of Certolizumab Pegol (CDP870) as Add-on Medication to Methotrexate in Japanese Rheumatoid Arthritis (RA) Patients

Study Overview
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Brief Summary
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The objectives of this study are to evaluate the safety and efficacy of certolizumab pegol as add-on medication to methotrexate over the long term in Japanese RA patients transferred from Study 275-08-001 (NCT00791999), and to evaluate the effects of different dosing regimens on the safety and efficacy of certolizumab pegol in American College of Rheumatology 20% (ACR20) responders who completed Study 275-08-001.

Detailed Description
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This study was initiated by Otsuka Pharmaceutical Co., Ltd and transferred to Astellas on 12/04/2012.

Official Title
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A Multicenter, Open-label, Long-term Safety Study of CDP870 to Evaluate the Safety and Efficacy of CDP870 Administered in Combination With Methotrexate (MTX) Over the Long Term in Patients With Active Rheumatoid Arthritis Transferred From the Efficacy Confirmatory Study (Study 275-08-001)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Certolizumab pegol
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who participated in Study 275-08-001 and meet all of the criteria described below. Patients who did not reach ACR20, and prematurely discontinued Study 275-08-001 at Week 16 or completed Study 275-08-001 by Week 24. Patients who are able to receive treatment with MTX, by Week 52. Exclusion Criteria: Patients who experienced an important protocol deviation as mentioned below during Study 275-08-001. Patients who received live or attenuated vaccines during Study 275-08-001(Except for influenza or pneumococcal vaccines). Patients who were found to have tuberculosis on a chest X-ray during Study 275-08-001. Patients who required treatment for the same infection at two or more different times during Study 275-08-001 Women who are pregnant, are lactating, of childbearing potential and wish to conceive during the study and post-study 3 months. Patients whom the investigator has decided to be inappropriate for participation in the study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Certolizumab pegol 200 mg<br>Participants received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks in combination with methotrexate for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Drug: Certolizumab pegol<br>* Subcutaneous (SC) injection<br>* Other names: Cimzia;Drug: Methotrexate<br>* Methotrexate dose between 6 to 8 mg/week.<br>|
| Experimental: Certolizumab pegol 400 mg<br>Participants received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks in combination with methotrexate for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Drug: Certolizumab pegol<br>* Subcutaneous (SC) injection<br>* Other names: Cimzia;Drug: Methotrexate<br>* Methotrexate dose between 6 to 8 mg/week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | An adverse event (AE) is any untoward medical occurrence in a participant administered study drug which did not necessarily have a causal relationship with the treatment. In this study, events that occurred between the time of informed consent and the start of study medication were included in the adverse events for Study 275-08-001. Any event existing prior to the initiation of study treatment that was aggravated after initiation of study treatment was handled as a new event. The investigator assessed the severity of each AE as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities. A serious adverse event is an AE that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. | From the first dosing of this study up to 12 weeks (84 days) after the last dosing. The dosing was allowed until launch of certolizumab pegol for RA in Japan. The maximum duration on study drug was 204 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | A participant was an ACR20 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-001) were met: ≥ 20% improvement in 68 tender joint count; ≥ 20% improvement in 66 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein (CRP). | Baseline (of Study 275-08-001), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) | 
| Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | A participant was an ACR50 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-001) were met: ≥ 50% improvement in 68 tender joint count; ≥ 50% improvement in 66 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein (CRP). | Baseline (of Study 275-08-001), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) | 
| Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | A participant was an ACR70 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-001) were met: ≥ 70% improvement in 68 tender joint count; ≥ 70% improvement in 66 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein (CRP). | Baseline (of Study 275-08-001), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) | 
| Change From Baseline in Disease Activity Score (DAS) 28 | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: 28 tender joint count; 28 swollen joint count; Erythrocyte sedimentation rate (ESR); Patient's global assessment of disease activity. To obtain the tender joint count and swollen joint count, 28 joints of the shoulder, elbow, wrist, metacarpophalangeal joints, thumb interphalangeal joints, proximal interphalangeal joints, and knee joints were examined. The data before study drug administration of 275-08-001 Study was utilized for Baseline. DAS28(ESR) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible ESR. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score of 3.2 or less indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. | Baseline (of Study 275-08-001), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) | 
| Change From Baseline in Modified Total Sharp Score (mTSS) | X-ray images of extremities (posteroanterior views of both hands and dorsoplantar views of both feet) were independently assessed by at least two radiographic readers. The degree of joint destruction was graded by assessing bone erosion in 44 joints and joint space narrowing (JSN) in 42 joints. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (complete collapse of bone). The score for erosion ranges from 0 to 160 in the hands and from 0 to 120 in the feet (the maximum erosion score for a joint in the foot is 10). The JSN score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. JSN, including subluxation, was scored from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The mTSS ranges from 0 (normal) to 448 (worst). | Baseline (of Study 275-08-001), Week 0 (of this study) and Week 100 | 

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