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Rheumatoid ArthritisPhase 3PreCePRANCT01864265

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

A Phase 3 study testing Certolizumab Pegol in people with Rheumatoid Arthritis, run by University of Erlangen-Nürnberg Medical School at 6 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Certolizumab Pegol
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
156 participants
Where
6 sitesin 3 countries
Study dates
Jul 2013to 10 Jan 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 21Show fewer
  • ≥ 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.
  • . Exclusion Criteria:
  • 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

Who cannot join

None listed.

Trial locations and contacts

6 sites in 3 countries.

6 sites in 3 countries

Germany4 sites

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

    Berlin, 10117

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

    Erlangen, 91054

  • Medizinische Universitätsklinik Freiburg Abteilung Rheumatologie und Klinische Immunologie

    Freiburg im Breisgau, 79106

  • Universitätsklinikum Leipzig AÖR Department Innere Medizin Sektion Rheumatologie

    Leipzig, 04103

Other trials in Germany

Portugal1 site

  • Hospitais da Universidade (SRHUC) Reumatologia

    Coimbra, 3000-075

Other trials in Portugal

Serbia1 site

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

    Belgrade, 11000

Other trials in Serbia

About this study

Official title: Prediction of Response to Certolizumab Pegol Treatment by Functional MRI of the Brain. A Multi-center, Randomized Double-blind Controlled Study Prediction of Response to Certolizumab-Pegol in RA (PreCePRA)

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.

Read the detailed description

Randomized double-blinded controlled multi-centre, study over 12 weeks, followed by a 12 weeks single blinded multicenter trial in 156 patients with RA with inadequate response to DMARD therapy. The study is composed of 3 arms with a 1:1:1 randomization at baseline: High functional MRI/400mg Certolizumab Pegol on week 0,2 and 4 followed by Certolizumab Pegol 200mg every two weeks for a total of 24 weeks; low functional MRI/400mg Certolizumab Pegol on week 0,2 and 4 followed by Certolizumab Pegol 200mg every two weeks for a total of 24 weeks with the possibility of early escape at week 12.

Patients who did not respond sufficiently according to EULAR response criteria (DAS28 reduction ≥ 1.2) to Certolizumab-Pegol (Treatment Arm A and Arm B) after 12 weeks will be off-Study and treated according to local guidelines.

Patients in the Placebo group with an EULAR response ≥ 1.2 reaching remission (DAS28 ≤ 2.6) will also be off study and treated according to the local guidelines or will be followed while they are in clinical remission. Patients with an EULAR response (DAS28 reduction ≥ 1.2) but not fulfilling the clinical remission criteria (DAS28 ≤ 2.6) will receive Certolizumab Pegol in week 12,14 and 16 with Certolizumab Pegol 400mg s.c. followed by s.c.injection of 200mg Certolizumab Pegol every two weeks till week 24.

In the situation that in one group sufficient patients will be randomized, fMRI done at screening, needs to be analyzed first to ensure that no further patient will be randomized with the randomization to the closed group. A blinded person, not involved either in the analysation of the fMRI nor in the treatment of the patients or the clinical assessments, will be responsible for the randomization list. If the next number on the randomization list represent the number of the closed group, the patient is not eligible for the study and will be treated according to local guidelines.

Being tested
Certolizumab Pegol, Placebo
Keywords
Rheumatoid arthritis, functional MRI, Prediction of Response, Certolizumab Pegol
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Certolizumab PegolDrug

    Also called Cimzia

    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.

  • PlaceboDrug

    Placebo will be administered according to the label of the biological

Study groups in NCT01864265
Study groupRoleWhat they receive
Certolizumab PegolActive comparatorNot described
Receives: Drug: Certolizumab Pegol; Drug: Placebo
PlaceboPlacebo comparatorNot described
Receives: Drug: Certolizumab Pegol; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months

Secondary outcomes (9)

  1. Remission

    Proportion of subjects in each treatment group reaching remission (defined as DAS28 < 2.6) after 1, 12 and 24 weeks

    Measured: 6 months

  2. Quality of Life

    HAQ of zero after 12 and 24 weeks to baseline

    Measured: 6 months

  3. SF36

    Mean and median SF-36 after 1, 12 and 24 weeks

    Measured: 6 months

  4. MRI

    Proportion of subjects in each treatment group with normal functional MRI after screening, week 12 and 24 weeks

    Measured: 6 months

  5. Normal fMRI

    Proportion of subjects in each treatment group with normal functional MRI after screening, 12 and 24 weeks

    Measured: 6 months

  6. Ultrasound score

    Mean and median ultrasound synovitis score after 1, 12 and 24 weeks

    Measured: 6 months

  7. Bold signal

    Mean and median ultrasound synovitis score after 1, 12 and 24 weeks

    Measured: 6 months

  8. Adverse events

    Type, frequency, severity and relationship of adverse events, serious adverse events or suspected unexpected serious adverse reactions to drugs used in this study

    Measured: 6 months

  9. Number of patients who discontinue Certolizumab-Pegol

    Number of subjects who prematurely discontinue Certolizumab-Pegol due to any adverse event

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 May 2013 (estimated)
  2. Study startJul 2013
  3. Primary completion30 Jun 2019
  4. Study completion10 Jan 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
156 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01864265
Sponsor's protocol ID
PreCePRA
Acronym
PreCePRA
Status last verified
Mar 2020
First submitted
21 May 2013
Last updated
10 Mar 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 40570879

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Certolizumab Pegol in people with Rheumatoid Arthritis, run by University of Erlangen-Nürnberg Medical School at 6 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Germany, Portugal, Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reaching low disease activity (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01864265, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2020.

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