|- candidate number||14856|
|- NTR Number||NTR3985|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||6-mei-2013|
|- Secondary IDs||11/203 METC VUmc|
|- Public Title||Onderzoek naar aflevering van 124-I-F8IL10 in ontstoken gewrichten.|
|- Scientific Title||A phase 0 single dose study to evaluate the pharmacokinetics/-dynamics and specific targeting properties of 124-I-F8IL10 in patients with active rheumatoid arthritis.|
|- hypothesis||To evaluate the targeting performance (including pharmacokinetics/-dynamics) of the human radiolabeled monoclonal-antibody cytokine fusion protein 124I-F8IL10 in 5 patients with rheumatoid arthritis, in a single dose study.|
|- Healt Condition(s) or Problem(s) studied||Rheumatoid arthritis|
|- Inclusion criteria||1. Patients aged ≥18 years;|
2. Diagnosis of RA according to ACR criteria;
3. Active RA (Disease Activity Score 28 >3.2);
4. Treatment with disease modifying anti-rheumatic drugs (DMARDS), biologicals and in addition, corticosteroids up to 10 mg daily and non-steroidal anti-inflammatory drugs (NSAIDs) is permitted, provided that there is a stable dose for at least 2 weeks;
5. All acute toxic effects of any prior therapy returned to classification mild according to MedDRA;
6. Sufficient hematologic, liver and renal function: total white cell count as well as ANC should be normal prior to start of the treatment, as well as liver function tests:
A. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, haemoglobin (Hb) ≥ 9.5 g/dL;
B. Alkaline phosphatase (AP), alanine aminotransferase (ALT) and/or aspartate aminotransferase < 3 x upper limit of reference range (ULN), and total bilirubin < 2.0 mg/dL;
C. Creatinine < 1.5 ULN or 24 h creatinine clearance > 50 mL/min.
7. Negative serum pregnancy test for females of childbearing age prior to starting treatment;
8. Male patients, who are potentially fertile, must agree to use adequate contraceptive methods at the beginning of the screening visit and continue until 3 months following the last treatment with the study drug;
9. Evidence of a personally signed and dated Ethics Committee-approved Informed Consent form indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study;
10. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
|- Exclusion criteria||1. Presence of active infections (e.g. requiring antibiotic therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study;|
2. Chronic active hepatitis (hepatitis B/C) or active autoimmune diseases other than RA;
3. Known primary or secondary immunodeficiency;
4. HIV positive patient;
5. Evidence of active malignant disease, malignancies diagnosed within the previous 5 years;
6. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris;
7. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria);
8. Irreversible cardiac arrhythmias requiring permanent medication;
9. Uncontrolled hypertension;
10. Ischemic peripheral vascular disease (Grade IIb-IV);
11. Severe diabetic retinopathy;
12. Recovery from major trauma including surgery within 4 weeks of administration of study treatment;
13. Known history of allergy to IL-10 or other intravenously administered human proteins/peptides/antibodies;
14. Pregnancy or breast feeding;
15. Any conditions that in the opinion of the investigator could hamper compliance with the study protocol;
16. Previous exposure to radioactivity with a yearly cumulative dose of ≥ 5 mSv.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||15-mei-2013|
|- planned closingdate||15-mei-2014|
|- Target number of participants||5|
|- Interventions||A single dose of 0.4 mg F8IL10 labeled with up to 2 mCi (74 MBq) Iodine-124, followed by three PET-CT scans and blood sampling.
|- Primary outcome||To evaluate the targeting performance (including pharmacokinetics/-dynamics) of the human radiolabeled monoclonal-antibody cytokine fusion protein 124I-F8IL10 in 5 patients with rheumatoid arthritis, in a single dose study.|
|- Secondary outcome||To investigate dosimetric parameters of arthritic joints and internal organs.|
|- Timepoints||PET-CT scan at 0.5-1, 24 and 72 hr after infusion of 124I-F8IL10.|
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| J. Laken, van der|
|- CONTACT for SCIENTIFIC QUERIES|| J. Laken, van der|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|- Brief summary||Background:|
Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease. Therapy of RA include NSAIDs, Disease modifying drugs (DMARDs) and biological compounds that target TNF-α and other inflammatory cytokines, B-cells or T-cells. However a substantial part of patients do not respond to these treatments or had to stop treatment due to drug-related adverse events, resulting in an unmet need for alternative therapies.
Interleukin-10 (IL-10) is a cytokine produced by activated monocytes and T cells which is deeply involved in the regulation of inflammatory responses and immune reactions. IL-10 has been considered an attractive candidate for therapeutic use based on its potent in vitro immunomodulating activities and proven effects in animal models of acute and chronic inflammation, autoimmunitiy, cancer and infectious disease.
In the F8IL10 molecule, IL-10 is coupled to the antibody fragment F8 which binds to the extra-domain A of fibronectin, selectively expressed at sites of inflammation. Upon administration to a patient, F8IL10 is supposed to accumulate at the site of arthritis and exhibit its biological function there.
1. Evaluation of the targeting performance of the human radiolabeled monoclonal-antibody cytokine fusion protein 124I-F8IL10 in 5 patients with RA;
2. Determine dosimetric parameters.
Patients and methods:
Patients: 5 patients with active RA.
Methods: intravenous infusion of 74MBq 124I-F8IL10 followed by PET-CT scanning at 0.5-1, 24 and 74h, including blood sampling for determination of pharmacokinetics.
|- Main changes (audit trail)|
|- RECORD||6-mei-2013 - 20-mei-2013|