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Still's Disease, Adult-OnsetPhase 2NCT02398435

Therapeutic Use of Tadekinig Alfa in Adult-onset Still's Disease

A Phase 2 study testing Tadekinig alfa (recombinant human IL-18 binding protein) in people with Still's Disease, Adult-Onset, run by AB2 Bio Ltd. at 20 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The objective of this study is to assess safety, tolerability and early signs of efficacy of the investigational drug Tadekinig alfa in Adult-onset Still's disease, a rare polygenic auto-inflammatory disorder for which treatment remains empirical. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Still's Disease, Adult-Onset
What is being tested?
Tadekinig alfa (recombinant human IL-18 binding protein)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
20 sitesin 3 countries
Study dates
Feb 2015to Jul 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients aged 18 years and older, diagnosed as AoSD based on the presence of the Yamaguchi criteria with active disease (see appendix 2), irrespective of the continuation of the permitted treatment mentioned below
  • 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.

Who cannot join

  • Patients with a first episode of AoSD with less than one month of therapy with Prednisone or sDMARDs
  • 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
Show all 14Show fewer
  • Women of childbearing potential who are unwilling to use highly effective birth control methods (see definition in Inclusion criteria above) up to 1 month after the end of her participation in the study.
  • 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

Trial locations and contacts

20 sites in 3 countries.

20 sites in 3 countries

Germany10 sites

  • Innere Medizin II - Rheumatologie Schlosspark-Klinik

    Berlin, 14059

  • Medizinische Klinik - Rheumatologie und Klinische

    Berlin

  • Universitätsklinikum Erlangen

    Erlangen, 91054

  • Asklepios Klinik Altona

    Hamburg, 22763

  • St. Elisabeth Gruppe GmbH Katholische Kliniken Rhein-Ruhr Rheumazentrum Ruhrgebiet

    Herne, 44649

  • Universitätsklinikum Jena Klinik für Innere Medizin III Rheumatologie/Osteologie

    Jena, 07747

  • Klinik Kirchheim

    Kirchheim unter Teck, 73230

  • Universitätsklinikum Schleswig-Holstein - Campus Lübeck

    Lübeck, 23538

  • UNIVERSITÄTSMEDIZIN der Johannes-Gutenberg-Universität Mainz I. Medizinische Klinik und Poliklinik Rheumatologie

    Mainz, 55131

  • LMU München

    München, 80336

Other trials in Germany

France7 sites

  • Hôpital Pellegrin

    Bordeaux, 33076

  • CHRU de Lille - Hôpital Claude Huriez

    Lille, 59037

  • Hôpital de la Croix Rousse

    Lyon, 69317

  • CHRU de Montpellier

    Montpellier, 34090

  • CHU de Nantes - Hôtel Dieu

    Nantes, 44093

  • CHU Paris-GH La Pitié Salpêtrière-Charles Foix - Hôpital Pitié-Salpêtrière

    Paris, 75651

  • Strasbourg University Hospital

    Strasbourg

Other trials in France

Switzerland3 sites

  • Hôpitaux Universitaires de Genève - HUG

    Geneva

  • CHUV hospital

    Lausanne

  • Immunologie-Zentrum de Zürich

    Zurich

Other trials in Switzerland

About this study

Official title: Open-label, Multicenter, Dose-escalating Phase II Study to Investigate the Safety, Tolerability, and Early Signs of Efficacy of Subcutaneous Administrations of Tadekinig Alfa (IL-18BP) in Patients With Adult -Onset Still's Disease (AoSD) During 12 Weeks

The objective of this study is to assess safety, tolerability and early signs of efficacy of the investigational drug Tadekinig alfa in Adult-onset Still's disease, a rare polygenic auto-inflammatory disorder for which treatment remains empirical.

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.

Read the detailed description

The hypothesis of this study considers high levels of IL-18 during active Adult-onset still's disease as the therapeutic target. Treatment with IL-18BP will permit to inhibit the pro-inflammatory cascade triggered by IL-18 and may help to manage the different components of the disease.

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.

Being tested
Tadekinig alfa (recombinant human IL-18 binding protein)
Keywords
Auto-inflammatory disease, Still's disease, Arthritis Rheumatoid, IL-18, interleukin-18, IL-18 binding protein
Medical subject headings
Still's Disease, Adult-Onset, Arthritis, Juvenile, Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tadekinig alfa (recombinant human IL-18 binding protein)Biological

    Patients received the study treatment three times a week subcutaneously.

Study groups in NCT02398435
Study groupRoleWhat they receive
Cohort 80 mgExperimentalCohort 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.
Receives: Biological: Tadekinig alfa (recombinant human IL-18 binding protein)
Cohort 160 mgExperimentalCohort 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.
Receives: Biological: Tadekinig alfa (recombinant human IL-18 binding protein)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety (adverse events)

    Safety assessments will be reported all along the study. The data safety monitoring board will assess Safety at 3 weeks and 12 weeks of treatment.

    Measured: 12 weeks after first administration

Secondary outcomes (1)

  1. Efficacy 9 Efficacious dose at 3 weeks will be considered if normalisation of body temperature and decrease of C-reactive protein (CRP) by more or equal to 50 percent of baseline values are achieved.)

    Efficacy is assessed by the principal investigator. Efficacious dose at 3 weeks will be considered if normalisation of body temperature and decrease of C-reactive protein (CRP) by more or equal to 50 percent of baseline values are achieved.

    At twelve weeks, the dose will be considered efficacious if normalisation of body temperature persists, and improvement in joint tenderness or swelling (more or equal to 20 percent) and a decrease of CRP and ferritin to reference values.

    Measured: 12 weeks after first administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2015 (estimated)
  2. Study startFeb 2015
  3. Primary completionJun 2016
  4. Study completionJul 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02398435
Sponsor's protocol ID
AOSD-2014-001
Status last verified
Aug 2016
First submitted
23 Feb 2015
Last updated
6 Dec 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 20020138

  • 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.

    PubMed 5315135

  • 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.

    PubMed 17538564

  • 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.

    PubMed 19028363

  • 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.

    PubMed 11263769

  • 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.

    PubMed 1578458

  • 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.

    PubMed 29472362

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tadekinig alfa (recombinant human IL-18 binding protein) in people with Still's Disease, Adult-Onset, run by AB2 Bio Ltd. at 20 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Germany, France, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety (adverse events) (time frame: 12 weeks after first administration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02398435, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2016.

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