Back to resultsEfficacy Confirmation Study of CDP870 in Early Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Placebo
CZP
methotrexate (MTX)
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Cimzia, Early RA, Certolizumab Pegol
Eligibility Criteria
Inclusion Criteria:
Subjects with RA as defined by the ACR/EULAR criteria (2010) who meet all of the following criteria:
- Subjects who developed RA within one year after onset of RA.
- Subjects who have never received MTX before (MTX naive)
- Subjects whose disease activity is moderate or higher (DAS28(ESR) ≥ 3.2）
- Subjects must satisfy at least two of the three criteria (Anti-CCP antibody positive, Rheumatoid factor positive, Presence of X-ray erosion） for poor prognostic factors. The anti-CCP antibody positive is essential for every patient.
Exclusion Criteria:
- Patients who have a diagnosis of any other type of inflammatory arthritis.
- Patients who have a secondary, non-inflammatory type of arthritis.
- Patients who have used with MTX, reflunomide, or any other biologics prior to the start of study drug administration.
- Patients who have NYHA (New York Heart Association) Class III or IV congestive heart failure
- Patients who currently have, or who have a history of, tuberculosis.
- Patients who have a high risk of infection (with a current infectious disease, a chronic infectious disease, a history of serious infectious disease)
- Patients who currently have, or have a history of, malignant tumor
- Female patients who are breastfeeding or pregnant, who are of childbearing potential
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
PBO + MTX
CZP + MTX
Arm Description
Participants who received placebo subcutaneously every two weeks (Q2W) at Weeks 0, 2, and 4; followed by placebo subcutaneously Q2W from Week 6 to Week 50 and an oral dose of MTX administered from Week 0 onwards
Participants who certolizumab pegol (CZP) subcutaneously at a loading dose of CZP 400 mg every 2 weeks (Q2W) at Weeks 0, 2, and 4; followed by a dose of CZP 200 mg subcutaneously Q2W from Week 6 to Week 50 and an oral dose of MTX administered from Week 0 onwards
Outcomes
Primary Outcome Measures
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52
Radiographs/X-rays of hands and feet (posteroanterior views of both hands and dorsoplantar views of both feet) were independently assessed by two radiographic readers. The degree of joint damage was graded by assessing bone erosion in 44 joints and joint space narrowing (JSN) in 42 joints.
The bone 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).
Secondary Outcome Measures
Change From Baseline in mTSS at Week 24
Radiographs/X-rays of hands and feet (posteroanterior views of both hands and dorsoplantar views of both feet) were independently assessed by two radiographic readers. The degree of joint damage was graded by assessing bone erosion in 44 joints and joint space narrowing (JSN) in 42 joints.
The bone 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).
Clinical Remission Rate: Percentage of Participants Meeting the Disease Activity Score-28 Joint Count (DAS28) Erythrocyte Sedimentation Rate (ESR) (DAS28[ESR]) Remission Criteria at Weeks 24 and 52
The DAS28(ESR) measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC);
28 swollen joint count (SJC);
ESR;
Patient's global assessment of disease activity (PtGADA).
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.
DAS28(ESR) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible ESR. A participant was considered to be in remission if DAS28(ESR) <2.6.
Last Observation Carried Forward" (LOCF) was applied.
Clinical Remission Rate: Percentage of Participants Meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Simplified Disease Activity Index (SDAI)-Based Remission Criteria at Weeks 24 and 52
The ACR/EULAR SDAI remission rate measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC);
28 swollen joint count (SJC);
Patient's global assessment of disease activity (PtGADA);
Physician's Global Assessment of Disease Activity (PhGADA);
C-reactive protein (CRP)
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.
A participant was considered to be in remission if SDAI ≤3.3.
Last Observation Carried Forward (LOCF) was applied.
Percentage of Participants Meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean-based Remission Criteria at Weeks 24 and 52
The ACR/EULAR Boolean-based remission rate measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC);
28 swollen joint count (SJC);
Patient's global assessment of disease activity (PtGADA);
C-reactive protein (CRP)
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.
A participant was considered to be in remission if all the criteria for each variable was met:TJC (in 28 joints) ≤1; SJC (in 28 joints) ≤1; CRP ≤1 mg/dl; PtGADA ≤1.
Last Observation Carried Forward (LOCF) was applied
Full Information
NCT ID
NCT01451203
First Posted
September 25, 2011
Last Updated
June 28, 2017
Sponsor
Astellas Pharma Inc
Collaborators
UCB Japan Co. Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT01451203
Brief Title
Efficacy Confirmation Study of CDP870 in Early Rheumatoid Arthritis
Official Title
A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of CDP870 in Patients With Early-stage Rheumatoid Arthritis Who Are Naïve to Methotrexate and Have Poor Prognostic Factors
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
October 11, 2011 (Actual)
Primary Completion Date
August 28, 2013 (Actual)
Study Completion Date
October 20, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Inc
Collaborators
UCB Japan Co. Ltd.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objective of this study is to assess the efficacy of certolizumab pegol (CZP) with methotrexate (MTX) compared with MTX-alone in patients with early-stage rheumatoid arthritis (RA) who are naive to MTX and have with poor prognostic factors, using inhibition of radiographically confirmed joint damage progression over a one-year period as a primary endpoint. Following a year of treatment with CZP plus MTX treatment, CZP will be discontinued, and the subjects will be monitored for one more year (the follow-up period) to investigate the sustainability of efficacy of CZP during the MTX monotherapy for exploratory purposes.
Detailed Description
This study was initiated by Otsuka Pharmaceutical Co., Ltd and transferred to Astellas on 12/04/2012.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Cimzia, Early RA, Certolizumab Pegol
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
319 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PBO + MTX
Arm Type
Placebo Comparator
Arm Description
Participants who received placebo subcutaneously every two weeks (Q2W) at Weeks 0, 2, and 4; followed by placebo subcutaneously Q2W from Week 6 to Week 50 and an oral dose of MTX administered from Week 0 onwards
Arm Title
CZP + MTX
Arm Type
Experimental
Arm Description
Participants who certolizumab pegol (CZP) subcutaneously at a loading dose of CZP 400 mg every 2 weeks (Q2W) at Weeks 0, 2, and 4; followed by a dose of CZP 200 mg subcutaneously Q2W from Week 6 to Week 50 and an oral dose of MTX administered from Week 0 onwards
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subcutaneous (SC)
Intervention Type
Drug
Intervention Name(s)
CZP
Other Intervention Name(s)
CDP870, certolizumab pegol, Cimzia®
Intervention Description
SC
Intervention Type
Drug
Intervention Name(s)
methotrexate (MTX)
Intervention Description
oral
Primary Outcome Measure Information:
Title
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52
Description
Radiographs/X-rays of hands and feet (posteroanterior views of both hands and dorsoplantar views of both feet) were independently assessed by two radiographic readers. The degree of joint damage was graded by assessing bone erosion in 44 joints and joint space narrowing (JSN) in 42 joints.
The bone 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).
Time Frame
Baseline and Week 52
Secondary Outcome Measure Information:
Title
Change From Baseline in mTSS at Week 24
Description
Radiographs/X-rays of hands and feet (posteroanterior views of both hands and dorsoplantar views of both feet) were independently assessed by two radiographic readers. The degree of joint damage was graded by assessing bone erosion in 44 joints and joint space narrowing (JSN) in 42 joints.
The bone 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).
Time Frame
Baseline and Week 24
Title
Clinical Remission Rate: Percentage of Participants Meeting the Disease Activity Score-28 Joint Count (DAS28) Erythrocyte Sedimentation Rate (ESR) (DAS28[ESR]) Remission Criteria at Weeks 24 and 52
Description
The DAS28(ESR) measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC);
28 swollen joint count (SJC);
ESR;
Patient's global assessment of disease activity (PtGADA).
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.
DAS28(ESR) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible ESR. A participant was considered to be in remission if DAS28(ESR) <2.6.
Last Observation Carried Forward" (LOCF) was applied.
Time Frame
Week 24 and Week 52
Title
Clinical Remission Rate: Percentage of Participants Meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Simplified Disease Activity Index (SDAI)-Based Remission Criteria at Weeks 24 and 52
Description
The ACR/EULAR SDAI remission rate measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC);
28 swollen joint count (SJC);
Patient's global assessment of disease activity (PtGADA);
Physician's Global Assessment of Disease Activity (PhGADA);
C-reactive protein (CRP)
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.
A participant was considered to be in remission if SDAI ≤3.3.
Last Observation Carried Forward (LOCF) was applied.
Time Frame
Week 24 and Week 52
Title
Percentage of Participants Meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean-based Remission Criteria at Weeks 24 and 52
Description
The ACR/EULAR Boolean-based remission rate measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC);
28 swollen joint count (SJC);
Patient's global assessment of disease activity (PtGADA);
C-reactive protein (CRP)
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.
A participant was considered to be in remission if all the criteria for each variable was met:TJC (in 28 joints) ≤1; SJC (in 28 joints) ≤1; CRP ≤1 mg/dl; PtGADA ≤1.
Last Observation Carried Forward (LOCF) was applied
Time Frame
Week 24 and Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects with RA as defined by the ACR/EULAR criteria (2010) who meet all of the following criteria:
Subjects who developed RA within one year after onset of RA.
Subjects who have never received MTX before (MTX naive)
Subjects whose disease activity is moderate or higher (DAS28(ESR) ≥ 3.2）
Subjects must satisfy at least two of the three criteria (Anti-CCP antibody positive, Rheumatoid factor positive, Presence of X-ray erosion） for poor prognostic factors. The anti-CCP antibody positive is essential for every patient.
Exclusion Criteria:
Patients who have a diagnosis of any other type of inflammatory arthritis.
Patients who have a secondary, non-inflammatory type of arthritis.
Patients who have used with MTX, reflunomide, or any other biologics prior to the start of study drug administration.
Patients who have NYHA (New York Heart Association) Class III or IV congestive heart failure
Patients who currently have, or who have a history of, tuberculosis.
Patients who have a high risk of infection (with a current infectious disease, a chronic infectious disease, a history of serious infectious disease)
Patients who currently have, or have a history of, malignant tumor
Female patients who are breastfeeding or pregnant, who are of childbearing potential
Facility Information:
City
Chubu Region
Country
Japan
City
Chugoku Region
Country
Japan
City
Hokkaido Region
Country
Japan
City
Kanto Region
Country
Japan
City
Kinki Region
Country
Japan
City
Kyushu Region
Country
Japan
City
Shikoku Region
Country
Japan
City
Tohoku Region
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Details of the IPD sharing plan for this study can be found at www.clinicalstudydatarequest.com.
Citations:
PubMed Identifier
28153828
Citation
Atsumi T, Tanaka Y, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Eguchi K, Watanabe A, Origasa H, Yasuda S, Yamanishi Y, Kita Y, Matsubara T, Iwamoto M, Shoji T, Togo O, Okada T, van der Heijde D, Miyasaka N, Koike T. Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation: 2-year results of the C-OPERA study, a phase III randomised trial. Ann Rheum Dis. 2017 Aug;76(8):1348-1356. doi: 10.1136/annrheumdis-2016-210246. Epub 2017 Feb 2.
Results Reference
derived
PubMed Identifier
26139005
Citation
Atsumi T, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka Y, Eguchi K, Watanabe A, Origasa H, Yasuda S, Yamanishi Y, Kita Y, Matsubara T, Iwamoto M, Shoji T, Okada T, van der Heijde D, Miyasaka N, Koike T. The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression. Ann Rheum Dis. 2016 Jan;75(1):75-83. doi: 10.1136/annrheumdis-2015-207511. Epub 2015 Jul 2.
Results Reference
derived
Links:
URL
https://www.astellasclinicalstudyresults.com/hcp/study.aspx?ID=CDP870-275-11-001/1226-CL-B001
Description
Link to results on Astellas Clinical Study Results Web site
Learn more about this trial
Efficacy Confirmation Study of CDP870 in Early Rheumatoid Arthritis
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