Adult -onset Still’s Disease (AoSD) MedDRA version: 18.1 Level: PT Classification code 10064056 Term: Still's disease adult onset System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: Tadekinig alfa
Product Code: IL-18 BP
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Tadekinig alfa
CAS Number: 220712-29-8
Current Sponsor code: IL-18 BP
Other descri
Sponsors
AB2 Bio Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients aged 18 years and older, diagnosed as AoSD based on the presence of the Yamaguchi criteria with active disease, 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 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 5 mg/day) for = 1 month) and/or synthetic sDMARDs (methotrexate at a dose of at least 10mg/week) 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 4 weeks is recommended Patients can maintain treatment with stable doses of Non-Steroidal anti-inflammatory Drugs (NSAIDs), Prednisone (stable dose of Prednisone (of at least 5 mg/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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 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 immunodeficiency diseases Patients suffering from immune-mediated inflammatory diseases, including autoimmune diseases such as RA, SLE, etc., or spondylarthropathies, or inflammatory bowel disease. Patients with white blood cell counts below 2’500 cells/mm3 Patients with Neutrophils below 1’000 cells/mm3 Concomitantly treated with biologicals 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 Active Macrophage Activation Syndrome (MAS) 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 and 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safe use of Tadekinig alfa in AoSD patients;Secondary Objective: To assess clinical efficacy To assess laboratory/biological evidence of efficacy;Primary end point(s): SAFETY AND TOLERABILITY END POINTS : Reports of adverse events: The incidence, nature and severity of AEs will be reported. Reports will be produced according to the MedDRA highest hierarchy / System Organ Class), Common Terminology Criteria for Adverse Events (CTCAE), (MedDRA Lowest Level Term), and grade of severity. Abnormal physical examination: body temperature, heart rate, arterial blood pressure, lymph node enlargement, and abdominal palpation with specific examination of liver and spleen, presence of skin rash. Electrocardiogram change since baseline (ECG): A 12-lead ECG will be performed. ECG registers will collect all observed abnormalities. Clinically significant abnormalities occurring during the study execution will be reported as AEs. Abnormal laboratory results: The Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) will be followed where SAEs are categories 3 and 4. Category 5 is death. For example: - SAE hemoglobin: 5.0-20.0 x ULN; >5 x ULN for > 2 weeks (Grade 3) and > 20.0 x ULN (Grade 4). - SAE kidney injury: Creatinine > 3 x baseline or > 4.0 mg/dl (grade 3), need of dialysis (grade 4). All clinically significant abnormal laboratory results or assessments (the above mentioned parameters and all other laboratory parameters considered clinically significant by the Investigator) must be followed until they resolve (return to normal or baseline values) or stabilise, or until they are judged by the Investigator to be no longer clinically significant. Immunogenicity evaluation: Generation of anti recombinant human interleukin 18 Binding protein (anti-rhIL-18BP) antibodies Serum Protein electrophoresis Local tolerability at the injection site evaluated by a standardized assessment during the visits (see appendix 6 of the st | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): EFFICACY END POINTS : 1) EARLY SIGNS OF EFFICACY AT 3 WEEKS 1.1 Clinical - Body temperature (normal rage is between 36.3 and 37.4°C measured in the armpit) (measured after discontinuation of NSAID treatment for 24h). Armpit daily temperature readings will be performed by the patient at 10.00 am and 6.00 pm. A patient diary will be used for the daily body temperature records performed by the patient at home - Skin rash (if present at screening). The physician will assess evaluation of skin rash as changes from baseline (unchanged, slightly decreased, markedly decreased, resolved). In the patient diary a daily self-assessment of the presence/absence and extension of the skin rash will be recorded. - Joint assessment (44 joint assessment for synovitis and tenderness) - Patient global assessment of disease activity - Physician global assessment of disease activity - Pain assessment on VAS - Fatigue assessment on VAS - Daily dose of prednisone or NSAIDs: % of initial daily dose to identify tapering down or discontinuation of Prednisone, and maintenance or discontinuation of NSAIDS (DMARDs should be maintained stable / No tapering allowed) - Health assessment questionnaire (HAQ-DI) - Quality of life on SF-36v2® 1.2) Laboratory: - Serum CRP - Serum amyloid (SAA) and Serum S100A8/A9, S100A12 (analysis for these biomarkers will be performed according to clinical outcomes) - Ferritin and glycosylated ferritin - Leukocyte counts (< 10 x 109 granulocytes/liter) - Serum levels of total IL-18, free IL-18, IL-18BP, IL-1Ra, IL-6, TNF-a 1.3) Composite Indices: - American College of Rheumatology (ACR) responses, i.e., change from baseline (ACR20, ACR50, ACR70) - Simplified Disease Activity Index (SDAI). The SDAI is the numerical sum of five outcome parameters: tender and swollen joint count (based on a 28-joint assessment), patient and physician global assessment of disease activity visual analogue scale (VAS) 0–10 cm and lev | — |
Countries
France, Germany, Switzerland
Contacts
Public ContactEduardo Schiffrin, Medical Director
AB2 Bio Ltd.
Outcome results
None listed