- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01864265
Prediction of Response to Certolizumab Pegol Treatment by Functional MRI of the Brain (PreCePRA)
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)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Berlin, Germany, 10117
- Charité - Universitätsmedizin Berlin; Campus Charité Mitte Klinik für Rheumatologie und klinische Immunologie Studienambulanz
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Erlangen, Germany, 91054
- University of Erlangen-Nuremberg, Department of Internal Medicine 3, Rheumatology & Immunology
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Freiburg, Germany, 79106
- Medizinische Universitätsklinik Freiburg Abteilung Rheumatologie und Klinische Immunologie
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Leipzig, Germany, 04103
- Universitätsklinikum Leipzig AÖR Department Innere Medizin Sektion Rheumatologie
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Coimbra, Portugal, 3000-075
- Hospitais da Universidade (SRHUC) Reumatologia
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Belgrad, Serbia, 11000
- Belgrade University School of Medicine Director of the Institute Institute of Rheumatology
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
. 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
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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.
Other Names:
Placebo will be administered according to the label of the biological
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Active Comparator: Certolizumab Pegol
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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.
Other Names:
Placebo will be administered according to the label of the biological
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Reaching low disease activity
Time Frame: 6 months
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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.
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6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Remission
Time Frame: 6 months
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Proportion of subjects in each treatment group reaching remission (defined as DAS28 < 2.6) after 1, 12 and 24 weeks
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6 months
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Quality of Life
Time Frame: 6 months
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HAQ of zero after 12 and 24 weeks to baseline
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6 months
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SF36
Time Frame: 6 months
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Mean and median SF-36 after 1, 12 and 24 weeks
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6 months
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MRI
Time Frame: 6 months
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Proportion of subjects in each treatment group with normal functional MRI after screening, week 12 and 24 weeks
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6 months
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Normal fMRI
Time Frame: 6 months
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Proportion of subjects in each treatment group with normal functional MRI after screening, 12 and 24 weeks
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6 months
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Ultrasound score
Time Frame: 6 months
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Mean and median ultrasound synovitis score after 1, 12 and 24 weeks
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6 months
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Bold signal
Time Frame: 6 months
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Mean and median ultrasound synovitis score after 1, 12 and 24 weeks
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6 months
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Adverse events
Time Frame: 6 months
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Type, frequency, severity and relationship of adverse events, serious adverse events or suspected unexpected serious adverse reactions to drugs used in this study
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6 months
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Number of patients who discontinue Certolizumab-Pegol
Time Frame: 6 months
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Number of subjects who prematurely discontinue Certolizumab-Pegol due to any adverse event
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6 months
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Collaborators and Investigators
Investigators
- Principal Investigator: Juergen Rech, MD, University of Erlangen-Nuremberg, Department of Internal Medicine 3, Rheumatology & Immunology
- Study Director: Georg Schett, MD, Prof., University of Erlangen-Nuremberg, Department of Internal Medicine 3, Rheumatology & Immunology
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PreCePRA
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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