Efficacy and Safety of Sorafenib in New-Onset Type 1 Diabetes Mellitus

Prior treatment

• Severe hypertension (systolic blood pressure \> 200 mmHg and/or diastolic blood pressure \> 110 mmHg, or those requiring the concurrent use of 3 or more antihypertensive medications);
• Have had any major surgery within 8 weeks prior to screening or will require major surgery during the study;
• Previous treatment with sorefenib or related multikinase inhibitor;
• Concurrent use of medications that affect cytochrome P450 3A4 or use of drugs that interact with sorefenib, leading to altered plasma concentrations of the drugs;

Other illness

• Non-Type 1 Diabetes Mellitus.
• Liver and renal dysfunction:
  • acute or chronic active hepatitis
  • alanine aminotransferase or aspartate aminotransferase \>2·0 times the upper limit of normal persisting for persisting for more than one week
  • impaired renal function defined by estimated glomerular filtration rate (according to the CKD-EPI) of \< 60 mL/min/1.73 m2
• History of severe gastrointestinal diseases such as gastrointestinal ulcers, gastrointestinal hemorrhage, pyloric stenosis, gastric bypass surgery, acute or chronic pancreatitis, etc;
• Anticipated ongoing use of diabetes medications other than insulin;
• Known hypersensitivity to sorafenib, or history of severe allergic reactions to other medications (e.g., anaphylaxis, angio-edema, or serious cutaneous drug reactions);
• Use of medications in the last month known to cause an ongoing change in the course of type 1 diabetes or immunological status (e.g., high-dose inhaled, extensive topical, or systemic glucocorticoids);
• Known coagulation disorders or use of anticoagulants (e.g., warfarin, rivaroxaban, or low molecular weight heparin);

Lab values

• Signs of chronic active infection (e.g., hepatitis, tuberculosis, cytomegalovirus, Epstein-Barr virus, herpes zoster, or toxoplasmosis), or screening laboratory evidence consistent with chronic active infection:
  • Positivity for human immunodeficiency virus
  • Positive purified protein derivative or interferon-γ release assay suggestive of tuberculosis
  • Positivity for hepatitis B surface antigen And acute infections (e.g., respiratory, urinary tract, or gastrointestinal infections) must be resolved before reevaluation;
• Previous or current cerebro-cardiovascular diseases:
  • Congestive heart failure (NYHA Class III-IV)
  • Myocardial infarction
  • unstable ischemic heart disease,
  • Arrhythmia
  • Syncope of cardiac or unknown origin
  • Structural defects
  • Signs of QT prolongation on electrocardiogram (450 ms in men, 470 ms in women)
  • Stroke
  • Transient Ischemic Attack
• Hematological conditions:
  • Anemia (hemoglobin below 120 g/L in men and 110 g/L in women)
  • Leukopenia (\<4000 leukocytes per μL)
  • Thrombocytopenia (\<100,000 platelets per μL)
  • Neutropenia (\<1500 neutrophils per μL)
• Abnormal coagulation function during the screening period: Prothrombin time (PT) is prolonged beyond the upper limit of normal for 3 seconds and/or activated partial thromboplastin time (APTT) is prolonged beyond the upper limit of normal for 10 seconds;

Other

• For men: unwilling to adopt contraception during the whole study period;
• For women:
  • Pregnancy or breastfeeding
  • Less than 100 days postpartum before enrollment
  • Unwilling to defer pregnancy during the 1-year study period
• Other situations in which the investigator considers it inappropriate to participate in this trial.

• Subjects with written informed consent;
• Age: 18-60 years;
• Diagnosis of T1DM according to ADA criteria within 1 year prior to starting study drug;
• Islet autoantibody positivity (one or more of GADA, IA-2A, ZnT8A);
• Stimulated C-peptide \> 200 pmol/L;
• Participants of childbearing age who are sexually active must agree to use of effective birth control until the end of the study