Therapeutic Use of Tadekinig Alfa in Adult-onset Still's Disease
NCT ID: NCT02398435
Last Updated: 2016-12-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
23 participants
INTERVENTIONAL
2015-02-28
2016-07-31
Brief Summary
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This disease is characterized by a daily spiking fever, arthralgia / arthritis, and skin rashes with frequent components of sore throat, lymphadenopathies and neutrophilic leukocytosis. The etiology is unknown. In addition to the above-mentioned clinical features, the diagnosis includes some laboratory components that reflect the systemic inflammation: high erythro-sedimentation rate, C-reactive protein, high serum ferritin and high levels of interleukin 18 (IL-18).
Tadekinig alfa is the drug name for recombinant human interleukin-18 binding protein (IL-18BP). This investigational drug was tested in healthy volunteers, psoriasis and rheumatoid arthritis patients in phase I studies. It demonstrated good safety and tolerability profile with only mild adverse events in the injection site.
Detailed Description
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This study is an open label, dose-finding study involving multiple centers in Europe. Two dose cohorts (80mg and 160mg) were treated during twelve weeks and followed-up for four more weeks.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Cohort 80 mg
Cohort 1 included 10 patients. Patients received Tadekinig alfa s.c with a dosage of 80mg. Safety assessments were conducted by data safety monitoring board. Non-responder patients were upscaled to next dose (160mg) after 3 weeks of treatment.
Tadekinig alfa (recombinant human IL-18 binding protein)
Patients received the study treatment three times a week subcutaneously.
Cohort 160 mg
Cohort 2 included 13 patients. all patients were treated with Tadekinig alfa s.c with a dosage of 160mg. Safety was evaluated by data safety monitoring board.
Tadekinig alfa (recombinant human IL-18 binding protein)
Patients received the study treatment three times a week subcutaneously.
Interventions
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Tadekinig alfa (recombinant human IL-18 binding protein)
Patients received the study treatment three times a week subcutaneously.
Eligibility Criteria
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Inclusion Criteria
* Patients with active disease will be considered if they exhibit at least two of the Yamaguchi's major criteria (see appendix 2) at the screening visit plus at least either fever or elevation of markers of inflammation (CRP ≥ 10 mg/L).
* Patients that have been exposed to NSAIDS, Prednisone (at least 5mg/day for ≥1 month) and/or synthetic sDMARDs (methotrexate at a dose of at least 10mg/day for ≥ 3 months) without response to treatment or with incomplete response to treatment
* Women of childbearing potential with negative pregnancy test at screening, V3, V4, V5 and V6 and that agree to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment. Birth control methods that are considered as highly effective are either: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence.
In each case of delayed menstrual period (over one month between menstruations, confirmation of absence of pregnancy is strongly recommended. This recommendation also applies to women of child bearing potential with infrequent or irregular menstrual cycles.
As regards the duration of contraception after the study, taking into account the median half-life of Tadekinig alfa of almost 40h, 5 half-lives represent duration of 200 hours. In order to be on the safe side, a post-study contraception duration of - Patients can maintain treatment with stable doses of Non-Steroidal anti-inflammatory Drugs (NSAIDs), Prednisone (stable dose of Prednisone of at least 5mg/day), and sDMARDs during Tadekinig alfa treatment (methotrexate at a dose of at least 10mg/week). Specifically baseline levels of prednisone treatment can be maintained or tapered (due to patient improvement), any requirement for prednisone increase during treatment will be considered a treatment failure.
* Ability to understand and willingness to sign a written informed consent
* Previous treatments with biologicals are allowed if the following wash-out periods are respected: one week for anakinra, two weeks for etanercept, and 6 weeks for, adalimumab, certolizumab, golimumab, tocilizumab, abatacept and 8 weeks for infliximab. Previous rituximab administration will require 6 months of washout and normal B-cell counts and previous treatment with canakinumab will require 6 months of washout.
* Inability to understand and unwilling to sign a written informed consent
* Any acute or chronic life-threatening disease: Such as cancer, and irreversible organ failures of heart, liver, lung and kidney (creatinine not higher than 1.5 X upper limit of normal).
* Patients having received adalimumab, certolizumab, golimumab, tocilizumab, abatacept within 6 weeks, infliximab within 8 weeks, canakinumab within 6 months, etanercept within 2 weeks, or anakinra 1 week prior to the start of Tadekinig alfa will not be enrolled into the study. Patients that have received rituximab within 6 months and/or have persistent low B-cell counts will not be eligible for enrolment.
* Subject who cannot be expected to comply with the study procedures
* Currently participating or having participated in another clinical trial during the last 4 weeks prior to the beginning of this study.
* Patients with no social security coverage
* Patients with a history of severe hypersensitivity reactions
Exclusion Criteria
* Patients with active or chronic infections (i.e. Tuberculosis (TB), HIV, HBV \& HCV)
* Patients suffering from inherited immunodefinciency diseases
* Patients suffering from immune-mediated inflammatory diseases, including RA, SLE, etc. or spondylarthropathies, or inflammatory bowel disease.
* Patients with white blood cell counts below 2'500 cells/mm3
* Concomitantly treated with biologicals
18 Years
65 Years
ALL
No
Sponsors
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AB2 Bio Ltd.
INDUSTRY
Responsible Party
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Principal Investigators
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Cem Gabay, Prof.
Role: PRINCIPAL_INVESTIGATOR
Hospital University of Geneva
Locations
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Hôpital Pellegrin
Bordeaux, , France
CHRU de Lille - Hôpital Claude Huriez
Lille, , France
Hôpital de la Croix Rousse
Lyon, , France
CHRU de Montpellier
Montpellier, , France
CHU de Nantes - Hôtel Dieu
Nantes, , France
CHU Paris-GH La Pitié Salpêtrière-Charles Foix - Hôpital Pitié-Salpêtrière
Paris, , France
Strasbourg University Hospital
Strasbourg, , France
Innere Medizin II - Rheumatologie Schlosspark-Klinik
Berlin, , Germany
Medizinische Klinik - Rheumatologie und Klinische
Berlin, , Germany
Universitätsklinikum Erlangen
Erlangen, , Germany
Asklepios Klinik Altona
Hamburg, , Germany
St. Elisabeth Gruppe GmbH Katholische Kliniken Rhein-Ruhr Rheumazentrum Ruhrgebiet
Herne, , Germany
Universitätsklinikum Jena Klinik für Innere Medizin III Rheumatologie/Osteologie
Jena, , Germany
Klinik Kirchheim
Kirchheim unter Teck, , Germany
Universitätsklinikum Schleswig-Holstein - Campus Lübeck
Lübeck, , Germany
UNIVERSITÄTSMEDIZIN der Johannes-Gutenberg-Universität Mainz I. Medizinische Klinik und Poliklinik Rheumatologie
Mainz, , Germany
LMU München
München, , Germany
Hôpitaux Universitaires de Genève - HUG
Geneva, , Switzerland
CHUV hospital
Lausanne, , Switzerland
Immunologie-Zentrum de Zürich
Zurich, , Switzerland
Countries
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References
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Bagnari V, Colina M, Ciancio G, Govoni M, Trotta F. Adult-onset Still's disease. Rheumatol Int. 2010 May;30(7):855-62. doi: 10.1007/s00296-009-1291-y. Epub 2009 Dec 18.
Bywaters EG. Still's disease in the adult. Ann Rheum Dis. 1971 Mar;30(2):121-33. doi: 10.1136/ard.30.2.121. No abstract available.
Efthimiou P, Kontzias A, Ward CM, Ogden NS. Adult-onset Still's disease: can recent advances in our understanding of its pathogenesis lead to targeted therapy? Nat Clin Pract Rheumatol. 2007 Jun;3(6):328-35. doi: 10.1038/ncprheum0510.
Fautrel B. Adult-onset Still disease. Best Pract Res Clin Rheumatol. 2008 Oct;22(5):773-92. doi: 10.1016/j.berh.2008.08.006.
Kawashima M, Yamamura M, Taniai M, Yamauchi H, Tanimoto T, Kurimoto M, Miyawaki S, Amano T, Takeuchi T, Makino H. Levels of interleukin-18 and its binding inhibitors in the blood circulation of patients with adult-onset Still's disease. Arthritis Rheum. 2001 Mar;44(3):550-60. doi: 10.1002/1529-0131(200103)44:33.0.CO;2-5.
Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, Kashiwazaki S, Tanimoto K, Matsumoto Y, Ota T, et al. Preliminary criteria for classification of adult Still's disease. J Rheumatol. 1992 Mar;19(3):424-30.
Gabay C, Fautrel B, Rech J, Spertini F, Feist E, Kotter I, Hachulla E, Morel J, Schaeverbeke T, Hamidou MA, Martin T, Hellmich B, Lamprecht P, Schulze-Koops H, Courvoisier DS, Sleight A, Schiffrin EJ. Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease. Ann Rheum Dis. 2018 Jun;77(6):840-847. doi: 10.1136/annrheumdis-2017-212608. Epub 2018 Feb 22.
Other Identifiers
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AOSD-2014-001
Identifier Type: -
Identifier Source: org_study_id