Efficacy Confirmation Study of CDP870 in Early Rheumatoid Arthritis

This study has been completed.
Sponsor:
Collaborator:
UCB Japan Co. Ltd.
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01451203
First received: September 25, 2011
Last updated: December 22, 2015
Last verified: December 2015
  Purpose
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.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: Placebo
Drug: CZP
Drug: methotrexate (MTX)
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Week 24 and Week 52 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Week 24 and Week 52 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Week 24 and Week 52 ] [ Designated as safety issue: No ]

    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



Enrollment: 319
Study Start Date: October 2011
Study Completion Date: October 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: PBO + MTX
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
Drug: Placebo
Subcutaneous (SC)
Drug: methotrexate (MTX)
oral
Experimental: CZP + MTX
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
Drug: CZP
SC
Other Name: CDP870, certolizumab pegol, Cimzia®
Drug: methotrexate (MTX)
oral

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

Ages Eligible for Study:   20 Years to 64 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01451203

Locations
Japan
Chubu Region, Japan
Chugoku Region, Japan
Hokkaido Region, Japan
Kanto Region, Japan
Kinki Region, Japan
Kyushu Region, Japan
Shikoku Region, Japan
Tohoku Region, Japan
Sponsors and Collaborators
Astellas Pharma Inc
UCB Japan Co. Ltd.
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01451203     History of Changes
Other Study ID Numbers: CDP870-275-11-001  JapicCTI-111636 
Study First Received: September 25, 2011
Results First Received: October 18, 2015
Last Updated: December 22, 2015
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Astellas Pharma Inc:
Early RA
Certolizumab Pegol
Cimzia

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Certolizumab Pegol
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 25, 2016