A Open Label, Parallel Group Phase IIA, Adaptive Design Study of MTX228 in Adult Subjects With Type 1 Diabetes and Preserved β-Cell Function
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Change in AUC C-peptide
研究概览
简要总结
MTX228 has been identified as a medication that might allow the re-growth of insulin producing beta cells in people with Type 1 Diabetes. Promoting the re-growth of lost beta cells would be beneficial to people with Type 1 Diabetes because it would allow them to take less insulin by injection and would improve their overall blood sugar control while reducing the risk and rate of low blood sugars. This open-label dose selection study aims to determine the optimal dose ofMTX228 for use in a future phase IIb study.
The purpose is to investigate the relative effectiveness of different doses of MTX228 and to select the most effective dose for further investigation in a phase 2b study.
详细描述
MTX228 was developed as a treatment for gastric ulcers but did not advance beyond phase 2 clinical trials because of lack of efficacy. Subsequently, MTX228 has been identified as an activator of Lyn kinase and was considered as a treatment for type 2 diabetes as an insulin sensitizer because of Lyn's interaction with insulin signaling molecules. More recently, Lyn has been identified as a critical regulator of beta-cell mass, with genetic and biochemical inactivation of Lyn provoking beta-cell death in isolated human islets and precipitated diabetes in mice, and activation of Lyn stimulating beta-cell survival and beta-cell proliferation. These findings strongly suggest that small molecule activators of Lyn, such as MTX228, could represent new therapeutic options to promote beta-cell regeneration in type 1 diabetes.
MTX228 has not been testing in clinical studies in type 1 diabetes and the optimal dose to use is not clear from the clinical trial in type 2 diabetes, where lower doses (100 mg once or twice daily) were more effective than higher doses (200 mg once or twice daily). The purpose of this study is to compare the effect of different doses of MTX228 in order to determine the most effective dose to move forward in a subsequent phase 2b study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •clinical diagnosis of T1DM with onset before the age of 35 requiring continuous treatment with insulin within 1 year of diagnosis and the presence of positive T1DM autoantibody titer if diagnosed after age 35 (past or present
- •HbA1c between 6.0 - 10.0 %.
- •Willing to wear study-provided CGM and share CGM data via cloud.
- •Diagnosis of T1DM ≥1year at time of screening.
- •Fasting or random (post-prandial) C-peptide level ≥ 100 pmol/l (or 0.3 ng/mL) during screening or pre-screening. Pre-screening C-peptide levels may be obtained by the study team (subject to patient's written consent) up to 56 days before planned enrolment to reduce the number of screen failures.
- •BMI ≤ 35 kg/m2
- •eGFR >45 ml/min/1.73m2
- •Able and willing to comply with the study protocol for the duration of the study
- •Written informed consent must be obtained before any study-related assessment is performed.
排除标准
- •Diagnosis or history indicative of monogenic, Type 2 or post-pancreatectomy diabetes
- •History of >1 episode of severe (level 3) hypoglycemia in the prior 6 months
- •Significant cardiovascular history defined as:
- •History of myocardial infarction, coronary angioplasty or bypass grafts, valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accidents within six months prior to entry into the study
- •Congestive heart failure defined as New York Heart Association (NYHA) stage III and IV
- •Uncontrolled hypertension defined as SBP > 160 mmHg and/or DBP > 100 mmHg
- •Symptomatic postural hypotension
- •Use of systemic corticosteroids (except physiologic replacement doses for adrenal insufficiency) or other medications that would influence insulin sensitivity
- •Use of non-insulin antihyperglycemic agents within prior 30 days.
- •History of significant other major or unstable neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, or urological disorder including previous solid organ or cell transplant that would impact patient safety or data interpretation.
- •History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years before screening (any history of treated cervical intraepithelial neoplasia is allowed)
- •Known recreational substance use or psychiatric illness that, in the opinion of the Investigator, may impact the safety of the subject or objectives with scheduled visits
- •A history of alcohol or drug abuse or drug addiction in the previous 12 months
- •A positive pregnancy blood test for women of childbearing age or breast-feeding women 12 Are unwilling to use an "effective" method of contraception during the course of the study. Sexually active male patients, who could have children, are required to use a condom or abstained from intercourse, and refrain from sperm donation for the purposes of conception. Females have to be surgically sterile (via hysterectomy or bilateral tubal ligation) or post-menopausal or using a medically acceptable barrier method of contraception (i.e. IUD, barrier methods with spermicide or abstinence).
研究组 & 干预措施
100 mg BID
Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg BID dose
干预措施: DEXCOM G6 (Device)
200 mg QD
Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 200mg BID dose
干预措施: DEXCOM G6 (Device)
100 mg QD
Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg QD dose
干预措施: DEXCOM G6 (Device)
100 mg BID
Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg BID dose
干预措施: MTX228 (Drug)
100 mg QD
Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg QD dose
干预措施: MTX228 (Drug)
200 mg QD
Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 200mg BID dose
干预措施: MTX228 (Drug)
结局指标
主要结局
Change in AUC C-peptide
时间窗: Days 0 and 84
C-peptide level as it relates to MTX228 doses Change in postprandial C-peptide level area under the curve (AUC), in a 2-hour Mixed Meal Tolerance Test (MMTT), between Days 0 and 84, as well as a change in AUC C-peptide between subjects receiving different doses of MTX228. Justification being that the ideal dose of MTX228 will cause the largest relative increase in C-peptide levels.
Dose selection for phase IIb study
时间窗: Days 0 and 84
A change in AUC C-peptide between subjects receiving different doses of MTX228 will determine the best doses Justification being that the ideal dose of MTX228 will cause the largest relative increase in C-peptide levels.
次要结局
- Lowered or increased total daily insulin dose(Days 84 and 168)
- To assess the time spent in a plasma glucose range of 3.9-10.0 mol/L(Days 84 and 168)
- Time spent in high range (10.1-13.9 mmol/L) and very high range (>13.9) based upon CGM in the last two weeks of the main treatment period and separately of the extended treatment(Days 84 and 168)
- Change in HbA1c(Days 84 and 168)
- Change in fasting plasma glucose (FPG)(Days 84 and 168)
- The number of episodes of level 2 and 3 hypoglycemia in study participants(Days 84 and 168)