UPADACITINIB for Polymyositis|Dermatomyositis|Antisynthetase syndrome|Overlap myositis|Immune-mediated necrotizing myopathy

Inclusion criteria

• {"criterion_text":"- 1.\tWritten informed consent"}
• {"criterion_text":"- 2.\tFemale and male subjects ≥ 18 and <=65 years of age at the time of signing the informed consent"}
• {"criterion_text":"- 3.\tPatients with clinical diagnosis of idiopathic inflammatory myopathies (IIM; including PM, DM, IMNM, ASyS, OM)"}
• {"criterion_text":"- 4.\tReceiving IVIG at stable dose and interval for at least 12 weeks before screening"}
• {"criterion_text":"- 5.\tStable disease activity according to the discretion of the treating physician for at least 3 months"}
• {"criterion_text":"- 6.\tReceiving a permitted background treatment for IIM including immunosuppressive drugs or antimalarials, corticosteroids (up to 10mg/day prednisone äquivalent ) with stable dose and interval for at least 12 weeks before enrollment"}
• {"criterion_text":"- 7.\tWilling and being capable of understanding and following the study procedures"}
• {"criterion_text":"- 8.\tFemale subjects agreeing to conduct efficient contraception, (unless they have no childbearing potential, means: o\tWomen who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation o\tWomen aged 55 years or older who are not on hormone therapy and who have had at least 6 months of spontaneous amenorrhea o\tWomen aged 55 years or older who have a diagnosis of menopause o Women with amenorrhoe >12 months)"}

Exclusion criteria

• {"criterion_text":"- 1.\tConditions other than IIM requiring continuous or intermittent treatment with IVIG such as primary or secondary immune deficiencies."}
• {"criterion_text":"- 18.\tSerologic evidence of current or past Hepatitis B, or Hepatitis C infection"}
• {"criterion_text":"- 19.\tEvidence of HIV infection and/or positive HIV antibodies"}
• {"criterion_text":"- 2.\tOther inflammatory rheumatic diseases (e.g. rheumatoid arthritis) that by discretion of investigator might interfere with conduction of the study"}
• {"criterion_text":"- 20.\tPositive QuantiFERON TB test, history of Tuberculosis, or active Tuberculosis-infection (without at least 4 weeks of adequate therapy for Tuberculosis and no history of re-exposure since their treatment was completed); patients must have no clinical features of active TB and have a screening chest x-ray with no evidence of active TB."}
• {"criterion_text":"- 21.\tAre largely or wholly incapacitated permitting little or no self-care, such as being bedridden or confined to wheelchair"}
• {"criterion_text":"- 22.\tAny major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening"}
• {"criterion_text":"- 23.\tPrimary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation"}
• {"criterion_text":"- 24.\tAny medical or psychological condition that in the opinion of the Principal Investigator would interfere with safe completion of the trial"}
• {"criterion_text":"- 25.\tHistory of any malignancy prior to screening and patients with an increased risk of malignancy, which, according to the investigator, would pose an unacceptable risk to the patient if participating in the study"}
• {"criterion_text":"- 26.\tPregnant women or nursing (breast feeding) mothers"}
• {"criterion_text":"- 10.\tPrevious treatment with a Janus kinase (JAK) inhibitor or tyrosine kinase (TYK) inhibitor (e.g. Baricitinib, Tofacitinib, Filgotinib, Deucravacitinib (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on a case-by-case basis)"}
• {"criterion_text":"- 27.\tFemale patients with reproductive potential not willing to use an effective method of contraception (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilisation) and are not willing to continue this precaution for the duration of the study until 6 months after receiving the last medication dose."}
• {"criterion_text":"- 28.\tHave a history of intravenous drug abuse, other illicit drug abuse, or chronic alcohol abuse within the 2 years prior to screening or are concurrently using, or expected to use during the study, illicit drugs (including marijuana)"}
• {"criterion_text":"- 29.\tNeuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation"}
• {"criterion_text":"- 3.\tMajor surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization."}
• {"criterion_text":"- 30.\tPatients with lack of peripheral venous access"}
• {"criterion_text":"- 31.\tPatients with known allergy or intolerance to the study drug or its’ excipients"}
• {"criterion_text":"- 4.\tScreening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator, are clinically significant and indicate an unacceptable risk for the patient´s participation in the study."}
• {"criterion_text":"- 5.\tHistory of venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE); myocardial infarction, unstable ischemic heart disease stroke, or New York Heart Association Stage III/IV heart failure."}
• {"criterion_text":"- 6.\tHistory of recurrent (≥ 2) VTE (DVT/PE)"}
• {"criterion_text":"- 7.\tPast or current cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders, or any other serious and/or unstable illness that in the opinion of the investigator could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data."}
• {"criterion_text":"- 11.\tPlasmapheresis within 12 weeks prior to screening."}
• {"criterion_text":"- 8.\tHistory of gastrointestinal organ perforation."}
• {"criterion_text":"- 9.\tImmunization with a live/attenuated vaccine within 12 weeks prior to baseline or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination at the discretion of the investigator)."}
• {"criterion_text":"- Patients currently smoking"}
• {"criterion_text":"- 12.\tAny of the following specific abnormalities on screening laboratory tests: a.\tALT or AST >3 x ULN (if not explained by IIM disease activity) b.\tAlkaline phosphatase (ALP) >3 x ULN c.\tTotal bilirubin ≥ 1.5 x ULN d.\tHemoglobin <8 g/dL e.\tTotal white blood cell count <2500 cells/µL (<2.50 x 103 / µL or <2.50 GI/L) f.\tNeutropenia (absolute neutrophil count [ANC] <1000 cells/ µL (<1.0 x 109/ L or <1.20 GI/L) g.\tLymphopenia (lymphocyte count <500 cells/µL) (<0.5 x 109/L or <50GI/L) h.\tThrombocytopenia (platelets <100,000 cells/µL) (<100 x 103/µL or <100 GI/L) i.\teGFR <30 mL/min/1.73 m2 In the case of any of the aforementioned laboratory abnormalities, the test may be repeated once by the central laboratory during screening and values resulting from repeat testing may be accepted for enrolment eligibility if they meet the eligibility criterion"}
• {"criterion_text":"- 13.\tSevere hepatic impairment."}
• {"criterion_text":"- 14.\tCurrent or recent (< 4 weeks prior to randomization) clinically serious viral, bacterial, fungal or parasitic infection or any other active or recent infection, that in the opinion of the investigator would pose an unacceptable risk to the patient if participating in the study"}
• {"criterion_text":"- 15.\tSymptomatic herpes simplex infection at the time of randomization"}
• {"criterion_text":"- 16.\tSymptomatic herpes zoster infection within 12 weeks prior to randomization"}
• {"criterion_text":"- 17.\tHistory of disseminated/complicated herpes zoster (for example, multidermatomal involvement, ophthalmic zoster, CNS involvement, or post-herpetic neuralgia)"}

Primary endpoints

• {"endpoint_text":"- To assess the proportion of patients in IVIG-free stable disease activity at week 16 after randomization across two study arms comparing Upadacitinib 30 mg vs Placebo.","definition_or_measurement_approach":"Proportion of patients in IVIG-free stable disease activity at week 16 after randomization comparing Upadacitinib 30 mg versus Placebo (as stated; no further operational definition provided in the JSON)."}

Secondary endpoints

• {"endpoint_text":"- •\tDifference in proportion of patients in IVIG-free stable disease activity at week 20 between patients with Upadacitinib versus Placebo","definition_or_measurement_approach":"Difference in proportion of patients meeting IVIG-free stable disease activity at week 20 between treatment arms."}
• {"endpoint_text":"- Different proportion of patients with IVIG-free stable disease activity at week 16 and 20 using different definitions of disease worsening: (1) worsening PhGA by ≥ 2 cm NRS and worsening MMT-8 by ≥ 20%, or (2) worsening EmGA by ≥ 2 cm NRS or (3) a worsening of 3 of the 6 core set measures (HAQ-DI, MMT-8, CK, PhGA, PtGA, EmGA) by ≥ 30%.","definition_or_measurement_approach":"Proportion using alternate definitions of disease worsening as specified (PhGA, MMT-8, EmGA, and core set measures thresholds) at weeks 16 and 20."}
• {"endpoint_text":"- •\tDifference in time to first flare between patients with Upadacitinib versus Placebo","definition_or_measurement_approach":"Time-to-event analysis comparing time to first clinical flare between arms."}
• {"endpoint_text":"- •\tDifference of manual muscle test between Upadacitinib and Placebo at week 16 and week 20","definition_or_measurement_approach":"Comparison of MMT-8 scores between arms at weeks 16 and 20."}
• {"endpoint_text":"- •\tDifference of patient reported outcomes, including 0- 10 numeric rating scale (NRS) of PtGA, EmGA, muscular pain, fatigue, dyspnoe and dysphagia; Quality of life, Health Assessment Questionaire Disability (HAQ-DI) between Upadacitinib and Placebo at week 16 and week 20","definition_or_measurement_approach":"Comparison of specified patient-reported outcomes (0-10 NRS scales, HAQ-DI, QoL measures) between arms at weeks 16 and 20."}
• {"endpoint_text":"- •\tDifference cumulative dose of steroids between patients with Upadacitinib versus Placebo at week 16 and 20","definition_or_measurement_approach":"Comparison of cumulative steroid dose between arms at weeks 16 and 20."}
• {"endpoint_text":"- •\tDifference in laboratory parameters of values (CK, ALT, AST, LDH and aldolase) between Upadacitinib and Placebo at week 16 and week 20","definition_or_measurement_approach":"Comparison of specified laboratory values (absolute and change from baseline) between arms at weeks 16 and 20."}
• {"endpoint_text":"- •\tDifferences in safety profile according to number of adverse events and organ systems (haematologic, hepatic, gastrointestinal, infections)","definition_or_measurement_approach":"Safety comparison by counts and classification of adverse events by organ system."}

Austria

Earliest CTIS Part Ii Submission Date

16-10-2024

Latest Decision Or Authorization Date

30-10-2024

Processing Time Days

14

Number Of Sites

1

Number Of Participants

10

Primary sponsor

Full Name

Medical University Of Vienna

Organisation Type

Educational Institution

Country Of Registered Address

Austria