Baricitinib for Patients With Intracerebral Hemorrhage

Efficacy and Safety Study of Baricitinib for Patients With Intracerebral Hemorrhage

This study is an investigator-initiated, prospective, randomized, open-label, blind end-point (PROBE) phase-2 clinical trial, to preliminarily evaluate the efficacy and safety of baritinib for the treatment of acute spontaneous intracerebral hemorrhage (ICH). Approximately 100 patients from different geographic sites across China will be recruited and randomized to 2 parallel arms in a 1:1 ratio to the intervention arm or control arm. The study will compare early additional baritinib 4-mg once daily (QD) administration to control arm with standardized treatments (background therapy), as novel agents for ICH in aimed subjects in immunological approach; and provide cortical evidence for further phase-3 clinical trials. The trial will be across up to approximately 15-month scope (12-month enrollment period and 3-month follow-up period). One independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data in all stages to make recommendations about early study closure or changes to study protocol.

• Inclusion criteria

  1. Participant (or legally authorized representative) who gives informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol;
  2. Are male or female patients from 18 years of age (inclusive), at the time of enrollment;
  3. Have acute, spontaneous, primary, supratentorial intracerebral hemorrhage (ICH), confirmed by head CT scan, at the time of enrollment;

• Exclusion criteria

  1. Have cerebellar or brainstem ICH;

  2. Have secondary ICH due to known or suspected structural abnormality in the brain, i.e., trauma, aneurysm, arteriovenous malformation, tumor;

  3. Have severe cerebral comorbidities, i.e., historical severe stroke, hydrocephalus, epilepsy;

  4. Have known advanced dementia or significant pre-stroke disability (modified Rankin Scale score of > 1);

  5. Have comorbidities might result in pulmonary or cardiac disorders, i.e., interstitial lung disease, chronic obstructive pulmonary disease, lung tumor, asthma, chronic respiratory failure, chronic heart failure;

  6. Have severe immunosuppression, defined as neutropenia (absolute neutrophil count < 1.0×10^9 cells/L) or lymphopenia (absolute lymphocyte count < 0.2×10^9 cells/L);

  7. Have chronic autoimmune disease, i.e., neuromyelitis optica spectrum disorders, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus;

  8. Have ever received attenuated live vaccination or immunological treatments (see below) within 4 weeks prior to the enrollment, or intend to receive measures above;

     • Cytotoxic treatments: cyclophosphamide, methotrexate, sulfasalazine, leflunomide, etc.;
     • Biological treatments: adalimumab, infliximab, etanercept (TNF-α inhibitors), tocilizumab (anti-IL-6), secukinumab (anti-IL-17), etc.;
     • Baricitinib and other JAK inhibitors: tofacitinib, abrocitinib, etc.;
     • Other treatments: convalescent plasma or intravenous immunoglobulin (IVIg), corticosteroids with dosage over alternative purpose, etc.;
     • Note: Non-steroid anti-inflammatory drugs (NSAID) are allowed;

  9. Have current or historical infections within 2 weeks prior to the enrollment, i.e., pneumonia, SARS-CoV-2 infections, current active tuberculosis; or have ever received antibiotics within 2 weeks prior to the enrollment;

  10. Have contraindications for baricitinib, i.e., severe anemia (hemoglobulin < 80g/L), decompensated kidney disease (eGFR < 30mL/min/1.73m^2), or severe liver injury with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times ULN;

  11. Have a current diagnosis of active malignancy, history of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) within 12 weeks prior to the enrollment or have a history of recurrent DVT/PE (≥ 2 times in total), which could constitute a risk when taking baricitinib in the opinion of the investigator;

  12. Are unlikely to finish the whole course of baricitinib administration in the opinion of the investigator (anticipated death or discharge);

  13. Are pregnant, or intend to become pregnant or breastfeed during the study;

  14. Are recruited for any other clinical trials;

  15. Are unsuitable for inclusion in the study in the opinion of the investigator.