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

Launched by SECOND XIANGYA HOSPITAL OF CENTRAL SOUTH UNIVERSITY · Jan 17, 2024

Keywords

ClinConnect Summary

This clinical trial is looking at a medication called Sorafenib to see if it can help people with new-onset Type 1 Diabetes Mellitus (T1DM). The main goal is to determine how effective and safe Sorafenib is for managing this condition. The trial is not yet recruiting participants, but when it does start, it will focus on adults aged 18 to 60 who have been diagnosed with T1DM in the past year and have certain markers in their blood that indicate their immune system is attacking their insulin-producing cells.

To be eligible for this study, participants will need to provide written consent and meet specific health criteria. They will also need to agree to use effective birth control if they are of childbearing age. Participants can expect to be closely monitored throughout the study to assess how well the medication works and whether it causes any side effects. It’s important to know that certain health issues, like severe infections or heart problems, might prevent someone from joining the trial. Overall, this study aims to explore a new potential treatment option for individuals facing the challenges of Type 1 Diabetes.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Subjects with written informed consent;
• • 2. Age: 18-60 years;
• • 3. Diagnosis of T1DM according to ADA criteria within 1 year prior to starting study drug;
• • 4. Islet autoantibody positivity (one or more of GADA, IA-2A, ZnT8A);
• • 5. Stimulated C-peptide \> 200 pmol/L;
• • 6. Participants of childbearing age who are sexually active must agree to use of effective birth control until the end of the study
• Exclusion Criteria:
• • 1. Non-Type 1 Diabetes Mellitus.
• 2. 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;
• • 3. 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);
• 4. 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
• 5. 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)
• • 6. 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;
• 7. 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
• • 8. History of severe gastrointestinal diseases such as gastrointestinal ulcers, gastrointestinal hemorrhage, pyloric stenosis, gastric bypass surgery, acute or chronic pancreatitis, etc;
• • 9. Have had any major surgery within 8 weeks prior to screening or will require major surgery during the study;
• • 10. Anticipated ongoing use of diabetes medications other than insulin;
• • 11. Known hypersensitivity to sorafenib, or history of severe allergic reactions to other medications (e.g., anaphylaxis, angio-edema, or serious cutaneous drug reactions);
• • 12. 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);
• • 13. Previous treatment with sorefenib or related multikinase inhibitor;
• • 14. 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;
• • 15. For men: unwilling to adopt contraception during the whole study period;
• 16. For women:
• • Pregnancy or breastfeeding
• • Less than 100 days postpartum before enrollment
• • Unwilling to defer pregnancy during the 1-year study period
• • 17. Known coagulation disorders or use of anticoagulants (e.g., warfarin, rivaroxaban, or low molecular weight heparin);
• • 18. Other situations in which the investigator considers it inappropriate to participate in this trial.