Rheumatoid Arthritis Treatment and Biopsy Study Assessing Certolizumab Pegol (Cimzia)

Open-Label Pre and Post Treatment Arthroscopic Synovial Biopsy Study for the Assessment of Certolizumab Pegol Immunomodulatory Synovial Effects on Select Biomarkers and Gene Expression

The purpose of this study is to conduct an Investigator-Sponsored Study to determine the potential immunomodulatory effects of Certolizumab Pegol (CZP) treatment at the site of disease activity (synovial lining) in subjects with rheumatoid arthritis (RA), using pre treatment and post treatment arthroscopic synovial biopsies and ex vivo on gene expression.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Certolizumab Pegol (CZP); Procedure: Arthroscopic synovial tissue biopsy

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Frederick, Maryland, United States, 21702
      • Arthritis Treatment Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed and dated informed consent document
• Subjects must be at least 18 years of age or older
• Subject must be willing and able to comply with scheduled visits, arthroscopy, laboratory tests, and other procedures
• Diagnosis of RA based on American College of Rheumatology (ACR) 1987 Revised Criteria
• Active disease at screening visit
• Methotrexate taken continuously for at least 12 weeks at a stable dosage
• Sexually active women of child-bearing potential and men whose partners are women of child-bearing potential are required to use adequate contraceptive methods during participation on this trial
• Treatment with non-steroidal anti-inflammatory drugs (NSAIDS)and oral corticosteroids (less than or equal to 10 mg/day prednisone or equivalent)is accepted

Exclusion Criteria:

• Diagnosis of any other inflammatory arthritis
• History of infected joint prosthesis that is still in situ
• History of allergy to local anesthetic agents
• Pregnant or lactating women
• Current or recent history of uncontrolled clinically significant conditions(e.g..,kidney disease, liver disease, class III or IV congestive heart failure, according to the New York Heart Association)
• History or suspected demyelinating disease of the central nervous system, e.g. multiple sclerosis or optic neuritis
• Current participation in clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Certolizumab Pegol (CZP); Certolizumab Pegol (CZP) liquid formulation 200 mg sc -(initial loading dose of 400 mg sc at 0 (Baseline), 2, and 4 weeks), then 200 mg sc every 2 weeks at 6, 8, and 10 weeks with arthroscopic synovial tissue biopsy pre- and post-treatment.

Drug: Certolizumab Pegol (CZP); CZP is an anti-TNF, humanized antibody Fab' fragment/polyethylene glycol(PEG)conjugate. CZP liquid formulation 200 mg sc -(initial loading dose of 400 mg sc at 0 (Baseline), 2, and 4 weeks), then 200 mg sc every 2 weeks at 6, 8, and 10 weeks.; Other Names: Brand Name: Cimzia; UCB product: Certolizumab Pegol (CDP870); Pre-filled syringe: NDC50474-710-79; Procedure: Arthroscopic synovial tissue biopsy; Subjects will undergo arthroscopy Pre and Post Treatment. The arthroscopy will be performed on a clinically inflamed joint. A single arthroscopy procedure using a small bore arthroscope will be conducted to obtain synovial tissue in each joint in all subjects. Local anesthesia will be used only. Two small incisions will be made to accommodate the arthroscope and other instruments. Synovial biopsies will be obtained using a motorized shaver.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Synovial TNFa, CXCL13, IL-8, IL-6, IL-1b, IL-10, IP-10, BCL3, CD3E, DUSP4, FOXP3, CD79A, CD138, MMP-3, and MMP-1 After 12 Weeks of Treatment With Certolizumab Pegol (CZP) in Patients With Rheumatoid Arthritis	Synovial tissue biopsy samples were taken at baseline and at 12 weeks after starting treatment with CZP. These samples were analyzed to determine the concentrations of select biomarkers and to determine the percent change in concentration from baseline to week 12.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Screening in Disease Activity Score (DAS) 28 ESR After 14 Weeks of Treatment	The DAS 28 ESR is a score calculated from the results of a 28-count joint assessment (total number of tender joint possible is 28, and total number of swollen joints possible is 28), the Erythrocyte Sedimentation Rate (ESR), and the Patient Global Assessment (measured using a 100 mm visual analogue scale, with the lowest possible score of 0 mm meaning the subject is not affected at all by arthritis and the highest possible score of 100 mm meaning the subject is severely affected by arthritis). A lower DAS 28 ESR indicates less active disease, and a higher DAS 28 ESR indicates more active disease. The DAS 28 ESR was calculated for each subject at the screening visit and at the Week 14 final visit. The percent change was then calculated for each patient, and a mean percent change for all subjects was determined.	Screening and Week 14

Collaborators and Investigators

• Sponsor: Nathan Wei, MD, FACP, FACR:
• Collaborators: University of California, San Diego
• Investigators: Principal Investigator: Nathan Wei, MD,FACP,FACR, Nathan Wei, MD, PA d/b/a Arthritis Treatment Center, 301-694-5800

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: June 14, 2011
• First Submitted That Met QC Criteria: June 16, 2011
• First Posted (Estimate): June 17, 2011

Study Record Updates

• Last Update Posted (Estimate): April 8, 2014
• Last Update Submitted That Met QC Criteria: February 26, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Biologic; Cimzia; Certolizumab Pegol; Arthroscopic Synovial biopsy; Office Based Procedure; Tumor Necrosis Factor (TNF); Anti-TNF
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Certolizumab Pegol
• Other Study ID Numbers: ATC2011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No