A Randomized, Placebo-controlled, Double-blind, In-patient Study to Evaluate Safety, Tolerability, and Pharmacodynamics of REMD-477 Following a Single Dose in Subjects With Type 1 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Changes from baseline in 24-hour insulin requirements on Day 1 relative to the two 24 hour periods post-treatment on Days 3 and 4, between the REMD-477 and placebo treated subjects, needed to maintain targeted glycemic control.
研究概览
简要总结
This is a randomized, placebo-controlled, double-blind study to evaluate safety, tolerability and pharmacodynamics of REMD-477 in subjects who have Type 1 diabetes and are currently receiving insulin treatment. This proof of concept study will determine whether glucagon receptor blockade using a single dose REMD-477 can improve short-term glucose homeostasis in people with Type 1 diabetes.
详细描述
The study will be conducted at two sites in the United States, and approximately 20 subjects with type 1 diabetes will be enrolled. Eligible subjects will be admitted to the clinical research unit, to carefully monitor blood glucose; and establish the baseline insulin requirement for maintaining targeted normoglycemia (postabsorptive: 90-120 mg/dL; and postprandial: <180 mg/dL).
The patients will then be subjected to a hyperglycemic period (250-300 mg/dL) by a stepwise reduction in insulin infusion. After receiving a single SC dose of REMD-477 or matching placebo in a double-blinded fashion, all subjects will be assessed for the post-treatment 24-hour insulin requirement needed to maintain targeted normoglycemia (postabsorptive: 90-120 mg/dL; and postprandial: <180 mg/dL); and to be monitored closely for safety, tolerability and targeted glycemic control, for a 48-hr period. After the in-patient residency period, subjects will return to the clinic for weekly out-patient safety follow-up visits for 8 weeks.
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)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women between the ages of 18 and 60 years old, inclusive, at the time of screening;
- •Females of non-child bearing potential must be ≥1 year post-menopausal (confirmed by a serum follicle-stimulating hormone (FSH) levels ≥ 40 IU/mL) or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception;
- •Male subjects must be willing to use clinically acceptable method of contraception during the entire study;
- •Body mass index between 18.5 and 26.9 kg/m2, inclusive, at screening;
- •Diagnosed with Type 1 diabetes for greater than 2 years, based on clinical history or as defined by the current American Diabetes Association (ADA) criteria;
- •HbA1c ≥6.0 % but <9.0 % at screening;
- •Fasting C-peptide <0.2 ng/mL;
- •Current use of insulin pump and willing to use continuous glucose monitoring (CGM) system (e.g. DexCom) throughout the entire study;
- •ALT and/or AST within <1.5x ULN at screening;
- •Serum amylase and lipase within normal limits at screening;
- •Able to provide written informed consent approved by an Institutional Review Board (IRB).
排除标准
- •History or evidence of clinically-significant disorder or condition that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;
- •Significant organ system dysfunction (e.g., clinically significant pulmonary or cardiovascular disease, anemia [Hemoglobin <10.0 g/dL], and renal dysfunction [eGFR <90 ml/1.73M2/min]);
- •Any severe symptomatic hypoglycemic event associated with a seizure or requiring help from other people or medical facility in the past 6 months;
- •Current or recent (within 1 month of screening) use of diabetes medications other than insulin;
- •Use of steroids and/or other prescribed or over-the-counter medications that are known to affect the outcome measures in this study or known to influence glucose metabolism;
- •Smokes tobacco;
- •Known sensitivity to mammalian-derived drug preparations, recombinant protein-based drugs or to humanized or human antibodies;
- •History of illegal drug use or alcohol abuse within the last 6 months or a positive drug urine test result at screening;
- •History of pancreatitis, pancreatic neuroendocrine tumors or multiple endocrine neoplasia;
- •History of pheochromocytoma, or family history of familial pheochromocytoma;
- •Known or suspected susceptibility to infectious disease (eg, taking immunosuppressive agents or has a documented inherited or acquired immunodeficiency);
- •Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C antibodies (HepC Ab);
- •Participation in an investigational drug or device trial within 30 days of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known, whichever period is longer;
- •Blood donor or blood loss >500 mL within 30 days of Day 1;
- •Women who are pregnant or lactating/breastfeeding;
- •Regular exercise >120 min/week within 14 days of Day 1;
- •Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits;
- •Family history of multiple endocrine neoplasia.
- •Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
Matching placebo
Administered as a single SC dose in subjects with Type 1 Diabetes
干预措施: Placebo Comparator (Biological)
REMD-477 Treatment A
Administered as a single SC dose in subjects with Type 1 Diabetes
干预措施: REMD-477 (Biological)
结局指标
主要结局
Changes from baseline in 24-hour insulin requirements on Day 1 relative to the two 24 hour periods post-treatment on Days 3 and 4, between the REMD-477 and placebo treated subjects, needed to maintain targeted glycemic control.
时间窗: Baseline (24 hour period on Day 1) and Days 3 and 4
Number of treatment emergent adverse events per subject, including changes in vital signs, physical and neurological examinations, laboratory safety tests and ECGs
时间窗: Baseline and 57 days
次要结局
- Changes from baseline over time of ALT.(Baseline and 57 days)
- Changes from baseline over time of amylase(Baseline and 57 days)
- Immunogenicity: Incidence of REMD-477 neutralizing and non-neutralizing antibodies(Baseline and 57 days)
- Changes from baseline over time of AST.(Baseline and 57 days)
- Changes from baseline over time of ALP.(Baseline and 57 days)
- Changes from baseline over time of lipase(Baseline and 57 days)
- Changes from baseline over time of total bilirubin.(Baseline and 57 days)