Prediction of Response to Certolizumab Pegol Treatment by Functional MRI of the Brain

NCT01864265 | Completed Phase 3 DMC

• 1 other identifier: PreCePRA
• Study Type: interventional
• Target: 156
• Locations: 3 countries
• Sites: 6

Brief Summary

By using functional MRI the investigators have recently shown that TNFi elicit rapid changes in brain function linked to the perception of RA \[5\]. Functional MRI represents a method allowing detecting tiny changes in neuronal activity by measuring alterations of blood flow in the context of neuronal activation. TNFi rapidly reversed the widespread activation of brain centers involved in pain such as the thalamus and the somatosensoric cortex, as well as those involved in the control, of mood and emotions such as the limbic system. Moreover, as small phase I study with 10 patients with RA showed that high brain activity detected in the functional MRI predicts clinical response to Certolizumab Pegol after 1 month, suggesting the central nervous system activity may be used as a tool to predict response to TNFi \[8\]. The rationale of this study is to test whether response to TNFi can be predicted by using functional MRI.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; functional MRI; Prediction of Response; Certolizumab Pegol

Outcome Measures

Primary Outcomes (1)

• Reaching low disease activity

  Proportion of patients who reach low disease activity according to the DAS28 (DAS28 \< 3.2) during the first 12 weeks of study participation according their screening CNS activity measured by functional MRI.

  6 months

Secondary Outcomes (9)

• Remission

  6 months

• Quality of Life

  6 months

• SF36

  6 months

• MRI

  6 months

• Normal fMRI

  6 months

Study Arms (2)

Certolizumab Pegol

ACTIVE COMPARATOR

Drug: Certolizumab Pegol; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Drug: Certolizumab Pegol; Drug: Placebo

Interventions

Certolizumab Pegol DRUG

Certolizumab Pegol (Cimzia®) is an engineered, humanized antibody-Fab'-fragment with specificity for human TNF-α, that is conjugated to polyethylene glycol (PEG). Certolizumab Pegol (Cimzia®) is a humanized antibody-Fab'-fragment that is produced in Escherichia coli and subsequently PEGylated to prolong its circulating half-time to be similar to that of an intact mAB. Certolizumab Pegol has a high affinity for TNF α with a Kd90pM and is an effective TNF α inhibitor. Certolizumab pegol does not neutralize TNFß (lymphotoxin), a related cytokine, and does not activate complement or kill cells via antibody-dependent cellular toxicity.

Also known as: Cimzia

Certolizumab Pegol; Placebo

Placebo DRUG

Placebo will be administered according to the label of the biological

Certolizumab Pegol; Placebo

Eligibility Criteria

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

You may qualify if:

• Understands and voluntarily signs an informed consent form
• Male or female, aged ≥ 18 years at time of consent
• Must be able to adhere to the study visit schedule and other protocol requirements
• Must satisfy the 2010 ACR/EULAR classification criteria for rheumatoid arthritis plus a disease duration of at least 6 months.
• Must have active RA with a DAS28 ≥3.2
• Must be RF and/or ACPA positive
• ≥ 3 swollen and/or tender joints of the hands
• At screening- visit patients should have been treated without alterations of therapy for at least three months with DMARDS (i.e. Methotrexate) with or without concomitant use of steroids).
• Glucocorticoids treatment up to 10mg prednisolone per day will be allowed at study entry.

You may not qualify if:

• Individuals not able to understand and follow study protocol and not able to voluntarily sign informed consent
• Individuals not willing to follow study protocol and sign informed consent
• Individuals with claustrophobia, tattoos containing metal, magnetic endoprostheses, surgery on bone in between a time interval \< 3 months.
• Patients treated before with any biological or small molecule or medication under investigation for the treatment of RA.
• Patients with serious or chronic infections within the previous 3 months
• Opportunistic infections within the 6 months before screening
• Cancer within the 5 years before screening (with the exception of treated and cured squamous or basal cell carcinoma of the skin)
• History of severe congestive heart failure
• Current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal (a.e.diverticulitis), endocrine, pulmonary, cardiac, neurologic or cerebral disease
• Transplanted organ (with the exception of corneal transplantation done more than 3 months before screening)
• Evidence of active tuberculosis

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (6)

Charité - Universitätsmedizin Berlin; Campus Charité Mitte Klinik für Rheumatologie und klinische Immunologie Studienambulanz

Berlin, 10117, Germany

Location

University of Erlangen-Nuremberg, Department of Internal Medicine 3, Rheumatology & Immunology

Erlangen, 91054, Germany

Location

Medizinische Universitätsklinik Freiburg Abteilung Rheumatologie und Klinische Immunologie

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Leipzig AÖR Department Innere Medizin Sektion Rheumatologie

Leipzig, 04103, Germany

Location

Hospitais da Universidade (SRHUC) Reumatologia

Coimbra, 3000-075, Portugal

Location

Belgrade University School of Medicine Director of the Institute Institute of Rheumatology

Belgrade, 11000, Serbia

Location

Related Publications (1)

• Hess A, Tascilar K, Schenker HM, Konerth L, Schonau V, Sergeeva M, Kreitz S, Prade J, Strobelt S, Selvakumar M, Kleyer A, Englbrecht M, Hueber AJ, Zaiss MM, Feist E, Burmester GR, Voll RE, Finzel S, Baerwald C, Rosch J, Behrens F, Koehm M, da Silva JAP, Damjanov N, Dorfler A, Schett G, Rech J. Disease-associated brain activation predicts clinical response to TNF inhibition in rheumatoid arthritis (PreCePra): a randomised, multicentre, double-blind, placebo-controlled phase 3 study. Lancet Rheumatol. 2025 Aug;7(8):e565-e575. doi: 10.1016/S2665-9913(25)00032-3. Epub 2025 Jun 23.

  PMID: 40570879 DERIVED

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

Study Officials

• Juergen Rech, MD

  University of Erlangen-Nuremberg, Department of Internal Medicine 3, Rheumatology & Immunology

  PRINCIPAL INVESTIGATOR

• Georg Schett, MD, Prof.

  University of Erlangen-Nuremberg, Department of Internal Medicine 3, Rheumatology & Immunology

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 21, 2013
• First Posted: May 29, 2013
• Study Start: July 1, 2013
• Primary Completion: June 30, 2019
• Study Completion: January 10, 2020
• Last Updated: March 10, 2020

Record last verified: 2020-03

Locations

DE (4); SE (1); PT (1)