A Phase 2, Randomised, Placebo Controlled Study Investigating the Efficacy of Baricitinib in New Onset Type 1 Diabetes Mellitus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 4
- 主要终点
- The primary endpoint of the study is the change from baseline of plasma C-peptide area under the curve (AUC) over 2 hours following a mixed meal.
研究概览
简要总结
Type 1 diabetes (T1D) results from the killing of insulin-producing pancreatic beta cells by cells of the immune system. The study aims to slow the progressive, immune-mediated loss of insulin-producing beta cells that occurs after clinical presentation. The investigators have identified a pathway that is important for immune cells to kill beta cells, and a drug that will block this pathway and prevent beta cell death. This drug, baricitinib, is already in clinical use for rheumatoid arthritis, and is currently in clinical trials for other diseases, including childhood autoimmune diseases. It is hypothesized that baricitinib treatment for 48 weeks will preserve beta cell function in children and young adults with recently-diagnosed T1D.
The trial aims to recruit 83 participants aged 10-30 years who have been recently diagnosed with T1D. Two thirds of the participants will be randomly assigned to receive baricitinib, one third will receive placebo. The trial will test if baricitinib can slow the progressive loss of insulin-producing beta cells in these patients. The primary objective is to determine if baricitinib can reduce the loss of meal-stimulated plasma C-peptide, a measure of beta-cell function. Maintaining endogenous insulin in recent-onset T1D improves glucose control and may lead to long-term improvements in glucose and lower rates of serious diabetes complications and death.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Prior to study initiation, an independent researcher is responsible for generating the randomization schedule. The randomization schedule including treatment group assignment (active or placebo) will be provided to the pharmacists at each one of the study sites. The study pharmacists will conceal the group assignment from study participants, investigators and study staff including the statistician.
入排标准
- 年龄范围
- 10 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged between 10 and 30 years (inclusive) at screening;
- •Diagnosis of T1D according to ADA criteria within 100 days prior to starting study drug;
- •Islet autoantibody positivity (one or more of: GADA, IA-2A, IAA (assessed within one week of commencing insulin therapy), ZnT8A);
- •Stimulated (peak or 90 min) C-peptide >0.2 nM during a 2-hour MMTT at the screening visit; or random C-peptide result >0.3 nM during the screening period.
- •Participants of childbearing age who are sexually active must agree to use of effective birth control until the end of the study;
- •Be able to read, understand and give written informed consent;
- •Be willing to comply with intensive diabetes management.
排除标准
- •Use of immunosuppressive or immunomodulatory therapies other than inhaled or topical glucocorticoids;
- •Current or past history of deep vein thrombosis or pulmonary embolism;
- •Impaired renal function defined by estimated glomerular filtration rate (according to the CKD-EPI) of < 60 mL/min/1.73 m2;
- •LDL cholesterol >4mmol/l;
- •Elevated liver function tests at screening:
- •Aspartate aminotransferase 2x ULN
- •Alanine aminotransferase 2 x ULN;
- •Clinically significant abnormal laboratory parameters at screening including but not limited to:
- •Hemoglobin < 8 g/L;
- •White blood cells <2500 cells/µl;
- •Lymphocyte count <750 cells/µl;
- •Platelets <50,000 cells/µl;
- •Neutrophils <1200cells/µL;
- •Known hypersensitivity to baricitinib;
- •Known malignancy with the exception of successfully treated non- metastatic basal cell and squamous cell carcinoma;
- •Pregnancy, a desire for pregnancy, breast feeding, or a desire to father a child during the study;
- •Patients with current or recent (within 12 weeks of screening) clinically significant comorbidity, including clinically serious viral, bacterial, fungal, or parasitic infection. Viral infections include HBV, HCV, EBV, HIV, recent herpes zoster and TB;
- •Treatment with any investigational product within 30 days or 5 half - lives (whichever is longer) prior to baseline visit, or concurrent participation in a clinical trial with an investigational product or device;
- •Experienced any of the following within 12 weeks of screening: myocardial infarction, unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure;
- •Any serious medical condition within the previous 4 weeks which places the participant at an unacceptable risk if he or she were to participate in the study or confounds the ability to interpret data from the study, including, but not limited to, symptomatic cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine, haematological and neurological conditions or psychiatric illness/social situations that would limit compliance with study requirements;
- •Have had any major surgery within 8 weeks prior to screening or will require major surgery during the study that, in the opinion of the investigator would pose an unacceptable risk to the participant;
- •History of chronic alcohol abuse or IV drug abuse or other illicit drug abuse within 2 years prior to screening.
研究组 & 干预措施
Baricitinib
Baricitinib is an oral JAK1/JAK2-selective inhibitor. Dosage: The dose of baricitinib is 1 x 4mg tablet once daily Duration of administration: 48 weeks Mode of administration: Orally, with or without food
干预措施: Baricitinib (Drug)
Placebo
One placebo tablet once daily for a duration of 48 weeks. Placebo tablets contain lactose monohydrate, microcrystalline cellulose, croscarmellose sodium and magnesium stearate.
干预措施: Placebo (Drug)
结局指标
主要结局
The primary endpoint of the study is the change from baseline of plasma C-peptide area under the curve (AUC) over 2 hours following a mixed meal.
时间窗: Measured at 48 weeks post commencement of intervention.
次要结局
- Change from baseline in mean daily insulin use over 7 consecutive days.(Measured during the 2 weeks prior to the assessment at weeks 12, 24, 48, 72 and 96 post commencement of intervention.)
- Change from baseline in plasma C-peptide AUC over 2 hours following a mixed meal.(Measured at weeks 12, 24, 72 and 96 post commencement of intervention.)
- Change from baseline in glycosylated haemoglobin (HbA1c) levels.(Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention.)
- Number of participants with responder status. Responder status is defined as glycosylated haemoglobin (HbA1c) less than or equal to 6.5 percent and mean daily insulin use less than 0.5 international units per kilogram per day (IU/kg/day).(Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention.)
- Change in estimated C-peptide (CPEST) from baseline. CPEST is calculated based on six variable routine measures: disease duration, BMI, insulin dose, HbA1c, fasting plasma C-peptide and fasting plasma glucose.(Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention.)
- Continuous glucose monitoring (CGM).(Measured at baseline, 12, 24, 48 and 96 weeks post commencement of intervention.)
- The composite outcome assessing both the frequency, and when relevant, the severity of all adverse events.(Adverse events will be monitored throughout the entire study duration at weeks 0, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72 and 96.)