Magnetic Resonance Image Verified Early Response to Certolizumab Pegol in Subjects With Active Rheumatoid Arthritis (RA)

NCT01235598 | Completed Phase 3 Results

• 2 other identifiers: RA00282009-013758-33
• Study Type: interventional
• Target: 41
• Locations: 4 countries
• Sites: 10

Brief Summary

Phase IIIb study to determine early response to Certolizumab Pegol (CZP) with Magnetic Resonance Imaging (MRI) score Outcome Measures in Rheumatoid Arthritis (RA) Clinical Trials (OMERACT) RA MRI Scoring System (RAMRIS) in subjects with RA.

Conditions

Rheumatoid Arthritis

Keywords

Cimzia®; CDP870; CZP; Certolizumab Pegol; Rheumatoid Arthritis; MRI

Outcome Measures

Primary Outcomes (5)

• Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 16 Compared to Baseline for Certolizumab Pegol Arm

  Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.

  From Baseline to Week 16

• Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 8 Compared to Baseline for Certolizumab Pegol Arm

  Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.

  From Baseline to Week 8

• Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 4 Compared to Baseline for Certolizumab Pegol Arm

  Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.

  From Baseline to Week 4

• Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 2 Compared to Baseline for Certolizumab Pegol Arm

  Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.

  From Baseline to Week 2

• Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 1 Compared to Baseline for Certolizumab Pegol Arm

  Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.

  From Baseline to Week 1

Secondary Outcomes (22)

• Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Initiation Rate of Enhancement (IRE)

  From Baseline to Week 16

• Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Maximal Enhancement (ME)

  From Baseline to Week 16

• Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Number of Voxels (Nvox) With Plateau and Washout Pattern

  From Baseline to Week 16

• Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16

  From Baseline to Week 16

• Percentage of Subjects Meeting the American College of Rheumatology 20 % Criteria (ACR20) at Week 16

  From Baseline to Week 16

Study Arms (2)

Placebo followed by Certolizumab Pegol (CZP)

OTHER

Placebo, saline solution for sc injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40

Other: Placebo; Biological: Certolizumab Pegol (CZP) 200 mg; Biological: Certolizumab Pegol (CZP) 400 mg

Certolizumab Pegol (CZP)

EXPERIMENTAL

Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40

Biological: Certolizumab Pegol (CZP) 200 mg; Biological: Certolizumab Pegol (CZP) 400 mg

Interventions

Placebo OTHER

Placebo provided for the first subcutaneous injection in single-use vials at Week 0 (2 vials required), then Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4 and 6, followed by Certolizumab Pegol (CZP) 200 mg every 2 weeks from Week 8 to Week 40

Also known as: PBO

Placebo followed by Certolizumab Pegol (CZP)

Certolizumab Pegol (CZP) 200 mg BIOLOGICAL

Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40

Also known as: Cimzia®, CZP, CDP870

Certolizumab Pegol (CZP); Placebo followed by Certolizumab Pegol (CZP)

Certolizumab Pegol (CZP) 400 mg BIOLOGICAL

Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40

Also known as: Cimzia®, CZP, CDP870

Certolizumab Pegol (CZP); Placebo followed by Certolizumab Pegol (CZP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with a diagnosis of adult-onset Rheumatoid Arthritis (RA) of at least 3 months duration but no longer than 15 years
• Subjects with an active adult Rheumatoid Arthritis disease
• Subjects who have been on Disease-Modifying Anti-Rheumatic Drug (DMARD) therapy for at least 12 weeks

You may not qualify if:

• Subject must not have a secondary, non-inflammatory type of musculoskeletal condition (eg, osteoarthritis or fibromyalgia) that in the investigator's opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the subject's primary diagnosis of Rheumatoid Arthritis (RA)
• Subject must not have a diagnosis of any other inflammatory arthritis (eg, psoriatic arthritis or ankylosing spondylitis)
• Subject must not have a history of an infected joint prosthesis at any time with prosthesis still in situ
• Subject must not have received more than 1 biological agent
• Subject must not have a history of lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease at any time
• Subject with known Tuberculosis (TB) disease, high risk of acquiring TB infection or latent TB infection
• Subject must not have a known hypersensitivity to any components of the investigational medicinal product
• Subject must not have contraindications for Magnetic Resonance Image (MRI) and contrast agent

Sponsors & Collaborators

• UCB Pharma: lead

Study Sites (10)

003

Frederiksberg, Denmark

Location

002

Hellerup, Denmark

Location

001

Hvidovre, Denmark

Location

016

Slagelse, Denmark

Location

012

Nijmegen, Netherlands

Location

010

Utrecht, Netherlands

Location

018

Warsaw, Poland

Location

019

Warsaw, Poland

Location

008

Gothenburg, Sweden

Location

004

Malmo, Sweden

Location

Related Publications (1)

• Ostergaard M, Jacobsson LT, Schaufelberger C, Hansen MS, Bijlsma JW, Dudek A, Rell-Bakalarska M, Staelens F, Haake R, Sundman-Engberg B, Bliddal H. MRI assessment of early response to certolizumab pegol in rheumatoid arthritis: a randomised, double-blind, placebo-controlled phase IIIb study applying MRI at weeks 0, 1, 2, 4, 8 and 16. Ann Rheum Dis. 2015 Jun;74(6):1156-63. doi: 10.1136/annrheumdis-2014-206359. Epub 2014 Dec 15.

  PMID: 25512675 DERIVED

Related Links

• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Certolizumab Pegol

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: UCB Clinical Trials Call Center
• Organization: UCB

+1 877 822 9493

Study Officials

• UCB Clinical Trial Call Center

  +1 877 822 9493 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2010
• First Posted: November 5, 2010
• Study Start: December 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: May 1, 2013
• Last Updated: March 12, 2014
• Results First Posted: February 5, 2014

Record last verified: 2014-02

Locations

NL (2); PL (2); DK (4); SE (2)