JAK 1/2 Inhibitor, Baricitinib, in the Treatment of Adult IIM

Exclusion Criteria

• •1. Participants with other types of inflammatory myopathies including:
• •* Drug induced myositis
• •* Inclusion body myositis
• •* Malignancy-associated myositis
• •* Immune-mediated necrotizing myopathy
• •2. Participants unable to participate in clinical assessments or provide biological specimens as per the study protocol
• •3. Participants where the use of bariticinib would be contraindicated
• •4. Participants with known allergies to IMP or excipients
• •5. Women with a positive pregnancy test on enrolment or prior to start of study drug administration
• •6. Women who are known to be pregnant or breastfeeding
• •7. Women of child bearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 1 week after treatment (Please see Appendix 3 for definitions and acceptable methods of contraception).
• •8. Current symptoms of severe, progressive, or uncontrolled renal, hepatic, haematological, gastrointestinal, pulmonary, cardiac, neurological, ophthalmologic or cerebral disease with the exception of those symptoms that are a manifestation of polymyositis or dermatomyositis.
• •9. Concomitant medical conditions that in the opinion of the investigator might place the subject at unacceptable risk for participation in this study.
• •10. Participants with a history of venous thromboembolism including deep vein thrombosis and pulmonary embolism.
• •11. Participants with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection), including carcinoma-in-situ. Existing non-melanoma skin cell cancers must be removed prior to IMP dosing. Participants with dermatomyositis need to be screened for malignancies according to routine procedures.
• •12. Participants who have a history of clinically significant drug or alcohol abuse. Subjects currently taking MTX who admit to consumption of more than an average of 1 alcoholic drink per day.
• •13. Participants with any serious bacterial infection (such as pneumonia, other renal infection and sinusitis), unless treated and resolved with antibiotics.
• •14. Participants with any chronic bacterial infection (such as pyelonephritis and chest infection with bronchiectasis) in the previous 12 weeks before screening.
• •15. Participants with active tuberculosis (TB) requiring treatment within the previous 3 years. Subjects with a positive PPD and/or Quantiferon assay at screening will not be eligible for the study unless they have completed at least 4 weeks of treatment for latent TB, have a negative chest x-ray at enrolment, and commit to completing the course during the study. Such cases should be discussed with a respiratory physician as per local guidelines. A PPD response that is equal to or greater than 10 mm should be considered a positive test, although more conservative criteria may be applied as determined by the clinical circumstance and investigator according to published guidelines and/or local standards endorsed by the medical society. PPD and/or Quantiferon positive participants who have previously completed treatment for latent tuberculosis according to the local guidelines may be considered for enrolment. Equivocal Quantiferon results will need to be discussed with a local respiratory physician.
• •16. Participants with herpes zoster that resolved less than 8 weeks prior to the screening visit.
• •17. Participants with evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at the screening visit, including subjects with evidence of Human Immunodeficiency Virus (HIV) infection, positive HepBsAg, HepBcAb or hepatitis C antibody.
• •18. Significant toxicities associated with concomitant or previous immunosuppressive/biologic therapy that would preclude subjects from participating and completing the study.
• •19. Participants with clinically apparent immunodeficiency syndrome, (IgA deficiency alone is not an exclusion criterion).
• •20. Participants with any of the following laboratory values at screening:
• •* Haemoglobin (Hb) \< 80 g/litre
• •* Absolute lymphocyte count (ALC) \< 500 cells/mm3
• •* Absolute neutrophil count (ANC) \< 1000 cells/mm3
• •* Platelets \<100,000/mm3 (100 x 109/L)
• •* Creatinine clearance \<30ml/min. Note: participants with creatinine clearance between 30-60mL/min should receive a reduced oral dose of 2mg baricitinib OD.
• •* Any other laboratory test results that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.
• •21. For participants previously treated with rituximab: B cell levels less than lower limit of normal as measured by Fluorescent Activated Cell Sorting (FACS) analysis.
• •22. For all participants who have received prior rituximab, a normal CD19 B cell count must be documented at the time of screening for this study.
• •23. Participants who have received treatment with any investigational drug within 28 days of the first dose of IMP.
• •24. Participants who have at any time received treatment with JAK/STAT inhibitors.
• •25. Administration of live/ attenuated vaccines in the 4 weeks prior to screening and during the study. Effect on vaccine efficacy or the risk of infection transmission is unknown. In addition, clinical safety has not been established.
• •26. Concomitant use of targeted biologic therapies at any time during the study.