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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01374971
• Other study ID #: ATC2011
• Status: Completed
• Phase: Phase 3
• First received: June 14, 2011
• Last updated: February 26, 2014
• Start date: September 2011
• Est. completion date: July 2012

Study information

• Verified date: February 2014
• Source: Arthritis Treatment Center, Maryland
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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.

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.

Locations

Country	Name	City	State
United States	Arthritis Treatment Center	Frederick	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Nathan Wei, MD, FACP, FACR:	University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No