Efficacy Confirmation Study of CDP870 in Early Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01451203
• Other study ID #: CDP870-275-11-001
• Secondary ID: JapicCTI-111636
• Status: Completed
• Phase: Phase 3
• First received: September 25, 2011
• Last updated: December 22, 2015
• Start date: October 2011
• Est. completion date: October 2014

Study information

• Verified date: December 2015
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 319
• Est. completion date: October 2014
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 64 Years

Eligibility

Inclusion Criteria:

• Subjects with RA as defined by the ACR/EULAR criteria (2010) who meet all of the following criteria:

1. Subjects who developed RA within one year after onset of RA.

2. Subjects who have never received MTX before (MTX naive)

3. Subjects whose disease activity is moderate or higher (DAS28(ESR) = 3.2)

4. 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Placebo
Subcutaneous (SC)
• CZP
SC
• methotrexate (MTX)
oral

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Inc	UCB Japan Co. Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Baseline and Week 52	No
Secondary	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).	Baseline and Week 24	No
Secondary	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.	Week 24 and Week 52	No
Secondary	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.	Week 24 and Week 52	No
Secondary	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	Week 24 and Week 52	No

External Links

•   Link to results on Astellas Clinical Study Results Web site