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

NCT01590966 | Completed Phase 3

• 2 other identifiers: 2012/2792009-017998-37
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Axial and Peripheral Spondyloarthritis; Rheumatoid Arthritis

Keywords

spondyloarthritis; Rheumatoid arthritis

Outcome Measures

Primary Outcomes (9)

• Biodistribution of Cimzia® after administration of radiolabeled Cimzia®.

  After performing the immunoscintigraphy there will be evaluation of the correlation between visualised joint inflammation on the one hand seen by clinical examination , on MRI and on ultrasound and on the other hand seen on the immunoscintigraphy.

  at baseline

• Percentage of remission in patients, treated with Cimzia® after 14 weeks.

  All patients will be treated with Cimzia®. A specific therapy strategy will be applied: the 10 patients with early spondyloarthropathy (axial and peripheral) that are in a clinical remission on 2 consecutive visites (= week 14, 26, 38 and 50) will stop treatment after a minimum of 26 weeks treatment. If these patients are not in a clinical remission at week 26, then they will be treated further with continuous administration. The 5 patients with active rheumatoid arthritis and 5 patients with already existing longer axial spondyloarthropathy get continuous administration.

  After 14 weeks of administration.

• Percentage of remission in patients, treated with Cimzia® after 26 weeks.

  All patients will be treated with Cimzia®. A specific therapy strategy will be applied: the 10 patients with early spondyloarthropathy (axial and peripheral) that are in a clinical remission on 2 consecutive visites (= week 14, 26, 38 and 50) will stop treatment after a minimum of 26 weeks treatment. If these patients are not in a clinical remission at week 26, then they will be treated further with continuous administration. The 5 patients with active rheumatoid arthritis and 5 patients with already existing longer axial spondyloarthropathy get continuous administration.

  After 26 weeks of administration.

• Percentage of remission in patients, treated with Cimzia® after 38 weeks.

  All patients will be treated with Cimzia®. A specific therapy strategy will be applied: the 10 patients with early spondyloarthropathy (axial and peripheral) that are in a clinical remission on 2 consecutive visites (= week 14, 26, 38 and 50) will stop treatment after a minimum of 26 weeks treatment. If these patients are not in a clinical remission at week 26, then they will be treated further with continuous administration. The 5 patients with active rheumatoid arthritis and 5 patients with already existing longer axial spondyloarthropathy get continuous administration.

  After 38 weeks of administration.

• Percentage of remission in patients, treated with Cimzia® after 50 weeks.

  All patients will be treated with Cimzia®. A specific therapy strategy will be applied: the 10 patients with early spondyloarthropathy (axial and peripheral) that are in a clinical remission on 2 consecutive visites (= week 14, 26, 38 and 50) will stop treatment after a minimum of 26 weeks treatment. If these patients are not in a clinical remission at week 26, then they will be treated further with continuous administration. The 5 patients with active rheumatoid arthritis and 5 patients with already existing longer axial spondyloarthropathy get continuous administration.

  After 50 weeks of administration.

• Duration of remission in patients, treated with Cimzia® after 14 weeks.

  All patients will be treated with Cimzia®. A specific therapy strategy will be applied: the 10 patients with early spondyloarthropathy (axial and peripheral) that are in a clinical remission on 2 consecutive visites (= week 14, 26, 38 and 50) will stop treatment after a minimum of 26 weeks treatment. If these patients are not in a clinical remission at week 26, then they will be treated further with continuous administration. The 5 patients with active rheumatoid arthritis and 5 patients with already existing longer axial spondyloarthropathy get continuous administration.

  After 14 weeks of administration.

• Duration of remission in patients, treated with Cimzia® after 26 weeks.

  All patients will be treated with Cimzia®. A specific therapy strategy will be applied: the 10 patients with early spondyloarthropathy (axial and peripheral) that are in a clinical remission on 2 consecutive visites (= week 14, 26, 38 and 50) will stop treatment after a minimum of 26 weeks treatment. If these patients are not in a clinical remission at week 26, then they will be treated further with continuous administration. The 5 patients with active rheumatoid arthritis and 5 patients with already existing longer axial spondyloarthropathy get continuous administration.

  After 26 weeks of administration.

• Duration of remission in patients, treated with Cimzia® after 38 weeks.

  All patients will be treated with Cimzia®. A specific therapy strategy will be applied: the 10 patients with early spondyloarthropathy (axial and peripheral) that are in a clinical remission on 2 consecutive visites (= week 14, 26, 38 and 50) will stop treatment after a minimum of 26 weeks treatment. If these patients are not in a clinical remission at week 26, then they will be treated further with continuous administration. The 5 patients with active rheumatoid arthritis and 5 patients with already existing longer axial spondyloarthropathy get continuous administration.

  After 38 weeks of administration.

• Duration of remission in patients, treated with Cimzia® after 50 weeks.

  All patients will be treated with Cimzia®. A specific therapy strategy will be applied: the 10 patients with early spondyloarthropathy (axial and peripheral) that are in a clinical remission on 2 consecutive visites (= week 14, 26, 38 and 50) will stop treatment after a minimum of 26 weeks treatment. If these patients are not in a clinical remission at week 26, then they will be treated further with continuous administration. The 5 patients with active rheumatoid arthritis and 5 patients with already existing longer axial spondyloarthropathy get continuous administration.

  After 50 weeks of administration.

Secondary Outcomes (3)

• Improvement in the tender and swollen joint count.

  26 weeks after baseline.

• Improvement in enthesitis

  26 weeks after baseline.

• Improvement in global measurements of disease activity.

  26 weeks after baseline.

Study Arms (1)

Patients with an active inflammatory joint disease

EXPERIMENTAL

In total there will be 20 patients included: 5 patients with active rheumatoid arthritis, 5 patients with active early axial spondyloarthritis, 5 patients with active early peripheral spondyloarthritis and 5 patients with active ankylosing spondylitis.

Drug: administration of Cimzia®; Drug: Immunoscintigraphy with radiolabeled Cimzia®.

Interventions

administration of Cimzia® DRUG

Patients will be treated with prefilled syringes containing each 200 mg/ml Cimzia® every 2 weeks which will be administered subcutaneously (The first 3 injections, a dosage of 400mg Cimzia® subcutaneously will be administered).

Patients with an active inflammatory joint disease

Immunoscintigraphy with radiolabeled Cimzia®. DRUG

All 20 patients will undergo an immunoscintigraphy with radiolabeled Cimzia®. Certolizumab pegol (Cimzia®) is an engineered humanized monoclonal antibody Fab' fragment with specificity for human TNF-α, manufactured in E. coli. The antibody fragment is subsequently purified and conjugated with high molecular weight polyethylene glycol (PEG) (40kDa). Lyophilized Cimzia® will be conjugated with S-HYNIC (a bifunctional chelator). The conjugate will be radiolabeled with Tc-99m by adding 0.1 mg Tricine, 0.01 mg SnSO4 and 750 MBq Tc-99m pertechnetate. A dose of 750 MBq Tc-99m Cimzia® will be injected intravenously.

Patients with an active inflammatory joint disease

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)
• 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
• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Ghent: lead
• UCB Pharma SA: collaborator

Study Sites (1)

Ghent University Hospital

Ghent, 9000, Belgium

Location

Related Publications (1)

• 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.

  PMID: 27403334 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Arthritis, Rheumatoid; Spondylarthritis

Interventions

Radioimmunodetection

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Spondylitis; Spinal Diseases; Bone Diseases

Intervention Hierarchy (Ancestors)

Radionuclide Imaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Radioisotope; Immunologic Techniques; Investigative Techniques

Study Officials

• Filip Van den Bosch, MD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2012
• First Posted: May 3, 2012
• Study Start: October 18, 2012
• Primary Completion: March 26, 2019
• Study Completion: August 20, 2019
• Last Updated: August 26, 2019

Record last verified: 2014-12

Locations

BE (1)