Prediction of response to Certolizumab Pegol treatment with MRI of the brain. A multi-center, randomized double-blind controlled study Prediction of response to Certolizumab-Pegol in Rheumatoid Arthritis (PreCePRA)

• Register: EUCTR
• Last refreshed on: 18 January 2021
• Main ID: EUCTR2013-000337-13-PT
• Date of registration: 11/11/2015
• Prospective Registration: Yes
• Primary sponsor: Universitätsklinikum Erlangen
• Public title: Prediction of response to Certolizumab Pegol treatment with MRI of the brain. A multi-center, randomized double-blind controlled study Prediction of response to Certolizumab-Pegol in Rheumatoid Arthritis (PreCePRA)
• Scientific 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) - PreCePRA
• Date of first enrolment: 13/11/2015
• Target sample size: 156
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000337-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Portugal, Serbia, United States

Contacts

• Name: Clinical Trial Unit, Med. 3
• Affiliation: Universitätsklinikum Erlangen

• Name: Clinical Trial Unit, Med. 3
• Affiliation: Universitätsklinikum Erlangen

Key inclusion & exclusion criteria

Inclusion criteria:
• Subjects must have a diagnosis of Rheumatoid Arthritis (RA), fulfilling the new ACR/EULAR classification criteria 2010 with disease duration for at least 24 weeks.
• Active RA with a DAS28 of >3.2
• =3 swollen and/or tender joints of the hands
• Subjects must be DMARD-IR (inadequate responder)
• Must understand and voluntarily sign an informed consent form including written consent for data protection
• Must be able to adhere to the study visit schedule and other protocol requirements
• Must be aged = 18 years at time of consent
• Glucocorticoids treatment up to 10 mg prednisolon per day will be allowed at study entry
• At screening-visit patients should have been treated without alterations of DMARD therapy (for at least three months) (i.e. Methotrexate) (with or without concomitant use of steroids).
• 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 156
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 treated with biological or investigational products before.
• Individuals with claustrophobia, tattoos containing metal, magnetic endoprotheses, surgery on bone in between a time interval < 3 months, patients in any condition not allowing for MRI scan.
• Current treatment with MMF or preparations still in development.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Any other autoimmune or inflammatory disease such as Psoriasis, SLE, PSS, MCTD, SpA, Behcet disease, vasculitis, autoimmune hepatitis or fibromyalgia
• Participation in another phase 1-4 treatment study for RA
• Patients who are younger than 18 years or are incapable to understand the aim, importance and consequences of the study and to give legal informed consent
• Pregnant or lactating female (Women with child bearing potential have to use a highly effective contraceptive measure (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices - IUDs) and continue its use for the time of exposure to the drug as required). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) are not acceptable
• Patients who possibly are dependent on the Principal Investigator or investigator
• 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
• Evidence of chronic or active hepatitis B or C



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with active Rheumatoid Artrhitis (DAS28 > 3.2) despite DMARD therapy
MedDRA version: 20.0 Level: LLT Classification code 10040107 Term: Seropositive rheumatoid arthritis System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Cimzia
Product Name: Cimzia
Pharmaceutical Form: Suspension for injection in pre-filled syringe
INN or Proposed INN: CERTOLIZUMAB PEGOL
CAS Number: 428863-50-7
Current Sponsor code: UCB SA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution and suspension for suspension for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: End of Study

Primary end point(s): 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.
Expected:
• Group 1 (high voxel count treated with Certolizumab
Pegol): 80%)
• Group 2 (low voxel count treated with Certolizumab
Pegol): 40%)
• Group 3 (high or low voxel count treated with placebo):
20%.)

Main Objective: The primary parameter of interest is the 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 baseline CNS activity measured by functional MRI.

Secondary Objective: To compare clinical responses to Certolizumab-Pegol in RA patients with high and low CNS activity in the functional MRI to placebo responses

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: End of Study

Secondary end point(s): • Proportion of subjects in each treatment group reaching remission (defined as DAS28 < 2.6) after 2 12 and 24 weeks
• Proportion of subjects in each treatment group reaching low disease activity (defined as DAS 28 <3.2) after 24 weeks
• Mean and median DAS28 after 2 12 and 24 weeks
• Proportion of subjects in each treatment group reaching HAQ of zero after 12 and 24 weeks
• Mean and median HAQ after 2 12 and 24 weeks
• Mean and median SF-36 after 2 12 and 24 weeks
• Proportion of subjects in each treatment group with normal functional MRI after screening, week 12 and 24 weeks
• Proportion of subjects in each treatment group with normal functional MRI after screening, 12 and 24 weeks
• Mean and median ultrasound synovitis score after 2, 12 and 24 weeks
• Mean and median ultrasound synovitis score after 2, 12 and 24 weeks
• Mean and median area of BOLD signal after screening, week 12 and 24 weeks
• Type, frequency, severity and relationship of adverse events, serious adverse events or suspected unexpected serious adverse reactions to drugs used in this study
• Number of subjects who prematurely discontinue Certolizumab-Pegol due to any adverse event
• Mean and median changes of hormones after 2, 12 and 24 weeks compared to fMRI results
• Mean and median changes of cytokines after 2, 12 and 24 weeks compared to fMRI results

Secondary ID(s)

PreCePra

2013-000337-13-DE

NCT01864265

Source(s) of Monetary Support

UCB Pharma SA

Ethics review

Status: Approved
Approval date: 13/11/2015
Contact: