Clinical trial NCT01590966: Scintigraphic Detection of the Biodistribution of Tumor Necrosis Factor With a Radiolabeled Anti-TNFα in Patients With Active Rheumatoid Arthritis and Active Axial and Peripheral Spondyloarthritis
Official title: Scintigraphic Detection of the Biodistribution of Tumor Necrosis Factor With a Radiolabeled Anti-TNFα in Patients With Active Rheumatoid Arthritis and Active Axial and Peripheral Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Axial and Peripheral Spondyloarthritis
Rheumatoid Arthritis
Keywords: spondyloarthritis
Rheumatoid arthritis
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: UCB Pharma SA
First posted: 2012-05-03
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this open-label monocentric explorative pilot trial the objective is to show the biodistribution of TNFα by administration of radiolabeled anti-TNFα in patients with active rheumatoid arthritis and spondylarthropathy. The anti-TNFα used in this trial is certolizumab pegol (Cimzia®), a pegylated Fab'-fragment of a monoclonal antibody with high specificity for TNFα. Certolizumab pegol will be radiolabeled with 99mTechnetium. The aim of this study is to show the TNFα triggered inflammation process in the inflamed joints, especially in patients who have very early joint damage where currently other imaging methods such as X-rays are not sensitive enough for detection.


Eligibility criteria: INCLUSION CRITERIA FOR RHEUMATOID ARTHRITIS PATIENTS (5 PATIENTS)

* Age between 18 and 70 years-old with documented diagnosis (clinical evaluation, x-ray hands and feet minimum 2 months before inclusion) of rheumatoid arthritis minimum 3 months and maximum 15 years according to ACR criteria 1987. At least 8 tender and 8 swollen joints with inadequate response to at least 2 disease-modifying antirheumatic drugs (DMARDs) of which one is Methotrexate (MTX). Methotrexate must have been administered at least 3 months before baseline and doses and route must be stable for at least 2 months before baseline. Minimum dosage of MTX is 10 mg weekly and maximum dosage is 25 mg weekly. HAQ (Health assessment Score) score at least 25 at baseline and DAS 28(Disease Activity Score) \> 3.7 at baseline.
* All patients are biological naïve patients.
* Negative for Tuberculosis (TB) (also in history) and negative screening for TB (Mantoux test / x-ray thorax)
* Female patients must be post-menopausal for at least 1 year or must underwent surgery so that they cannot become pregnant. Women of child bearing potential must use adequate contraception throughout the study and 12 weeks after the last dose of certolizumab pegol.
* Patient need to understand the study and sign an informed consent form approved by the ethics committee before participation in this study.

INCLUSION CRITERIA FOR PATIENTS WITH AXIAL SPONDYLARTHROPATY (15 PATIENTS)

* Age between 18 and 70-years old with presence of a documented diagnosis of spondylarthropathy according to current ASAS criteria valid for all of the 3 sub-groups (early axial, early peripheral and established axial)
* 10 patients with axial SpA must fulfill current ASAS criteria for AxSpA and 5 of them need to fulfill the current modified New York criteria:

  * Chronic low back pain \> 3 months and onset of age \< 45 years
  * Active inflammatory injury on sacro-iliac joints on MRI. Active inflammatory injuries are defined as oedema of bone in or around the sacro-iliac joints, compatible with active injuries seen on axial SpA with STIR (short tau inversion recovery) MRI
  * Inadequate response on previously, optimal use of min 2 Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) in a anti-inflammatory dosage during 3 months or a medical contra-indication for use of NSAIDs
  * BASDAI score ≥ 4
* 5 patients with peripheral SpA must have presence of clinical peripheral arthritis or enthesitis or dactylitis with active disease activity, even under a stable dose of sulfasalazine during 3 months AND presence of one of the following:

  * Psoriasis of skin
  * Inflammatory bowel disease
  * Positive HLA B27
  * sacro-iliitis on image (X-ray or MRI of the sacro-iliac joints)
* all patients are anti-TNF naive
* No active tuberculosis (in medical history as current) and negative screening for latent TB (Mantoux test and X-ray thorax).
* Female patients must be post-menopausal for at least 1 year or must underwent surgery so that they cannot become pregnant. Women of child bearing potential must use adequate contraception throughout the study and 12 weeks after the last dose of certolizumab pegol.
* Patient need to understand the study and sign an informed consent form approved by the ethics committee before participation in this study.

EXCLUSION CRITERIA FOR RHEUMATOID ARTHRITIS AND SPONDYLOARTHROPATHY PATIENTS

* Patients cannot have treatment with experimental biological and non-biological therapy in the last 3 months or 5-times the half-live prior to baseline visit
* Patients who had previously treatment with anti-TNF
* Patients who had previously treatment with rituximab and/or abatacept
* Known hypersensitivity to certolizumab pegol (Cimzia®) or one of it compounds
* Current or recent medical history of progressive uncontrolled renal, hepatic, hematological, gastro-intestinal, endocrine, pulmonary, cardial, neurological or cerebral diseases.
* Severe or life threatening infections in the last 6 months; signs of current or recent infection
* Active or latent tuberculosis: in case one or more of the 3 criteria are positive: medical history of TB, recent (\< 6 months) X-ray chest or recent positive PPD skin
* Known history or current viral hepatitis B of hepatitis C
* Known HIV infection
* Malignancy or history of a malignancy
* History of lymph-proliferative disease or signs/symptoms suggestive fort his disease.
* Moderate to severe hart failure (NYHA-class III/IV)

Primary outcomes:
measure: Biodistribution of Cimzia® after administration of radiolabeled Cimzia®.
timeFrame: at baseline
measure: Percentage of remission in patients, treated with Cimzia® after 14 weeks.
timeFrame: After 14 weeks of administration.
measure: Percentage of remission in patients, treated with Cimzia® after 26 weeks.
timeFrame: After 26 weeks of administration.
measure: Percentage of remission in patients, treated with Cimzia® after 38 weeks.
timeFrame: After 38 weeks of administration.
measure: Percentage of remission in patients, treated with Cimzia® after 50 weeks.
timeFrame: After 50 weeks of administration.
measure: Duration of remission in patients, treated with Cimzia® after 14 weeks.
timeFrame: After 14 weeks of administration.
measure: Duration of remission in patients, treated with Cimzia® after 26 weeks.
timeFrame: After 26 weeks of administration.
measure: Duration of remission in patients, treated with Cimzia® after 38 weeks.
timeFrame: After 38 weeks of administration.
measure: Duration of remission in patients, treated with Cimzia® after 50 weeks.
timeFrame: After 50 weeks of administration.
Secondary outcomes:
measure: Improvement in the tender and swollen joint count.
timeFrame: 26 weeks after baseline.
measure: Improvement in enthesitis
timeFrame: 26 weeks after baseline.
measure: Improvement in global measurements of disease activity.
timeFrame: 26 weeks after baseline.
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital
Study officials:
affiliation: University Hospital, Ghent
name: Filip Van den Bosch, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Carron P, Lambert B, Van Praet L, De Vos F, Varkas G, Jans L, Elewaut D, Van den Bosch F. Scintigraphic detection of TNF-driven inflammation by radiolabelled certolizumab pegol in patients with rheumatoid arthritis and spondyloarthritis. RMD Open. 2016 Jun 24;2(1):e000265. doi: 10.1136/rmdopen-2016-000265. eCollection 2016.