A Phase 3, Randomized, Double-Blind, Parallel Group Safety Trial to Evaluate the Immunogenicity of Dasiglucagon and GlucaGen® Administered Subcutaneously in Patients With Type 1 Diabetes Mellitus (T1DM)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 7
- 主要终点
- Percentage of Patients With ADA
研究概览
简要总结
The trial's objective is to evaluate the immunogenicity of repeated single doses of dasiglucagon* and GlucaGen following subcutaneous (SC) administration in patients with type 1 diabetes mellitus (T1DM) and further to evaluate the safety and tolerability of dasiglucagon and GlucaGen.
*dasiglucagon is the proposed International Nonproprietary Name (pINN) for ZP4207
详细描述
Patients with T1DM were randomly assigned in a 1:1 ratio to receive 3 SC injections of either dasiglucagon (0.6 mg) or GlucaGen (1 mg), with 1 week between doses. Patients were followed for 15 weeks from the day of the first dose to assess the immune response. Patients with previous exogenic glucagon exposure were not excluded from the trial, but the information on previous glucagon administration was recorded to enable subgroup analyses. It was expected that 112 patients in total would be randomly assigned to treatment groups and treated. A total of 90 patients were expected to complete the trial (45 in each treatment arm). To qualify as completed, the patient had to be dosed according to the procedure described in the protocol and to have blood drawn for the antidrug antibody analyses as scheduled.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent obtained before any trial-related activities (trial-related activities are any procedure that would not have been performed during normal management of the patient)
- •Availability for the entire trial period
- •Age between 18 and 70 years, both inclusive
- •Male or female patients with T1DM for at least 1 year. Diagnostic criteria as defined by the American Diabetes Association
- •Hemoglobin A1c (HbA1c) <10%
- •Stable anti-diabetic treatment for at least 1 month (e.g. within 10% insulin dose adjustment)
排除标准
- •Previous administration of dasiglucagon (previously referred to as ZP4207)
- •Known or suspected allergy to trial medication(s) or related products
- •History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema)
- •Previous participation (randomization) in this trial
- •Females who are pregnant according to a positive pregnancy test, actively attempting to get pregnant, or are lactating
- •Patients on a closed loop artificial pancreas
- •Receipt of any investigational drug within 3 months prior to screening
- •Active malignancy within the last 5 years
- •Congestive heart failure, New York Heart Association class II-IV
- •Inadequately treated blood pressure as defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥90 mmHg at screening
- •Current bleeding disorder, including use of anticoagulant treatment
- •Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin-secreting pancreas tumor)
- •Known or suspected HIV infection
- •Use of a systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial
- •Use of systemic corticosteroids, anti-inflammatory biological agents, kinase inhibitors or other immune modulating agents within the last 3 months prior to screening
- •Donation of blood or plasma in the past month, or in excess of 500 mL within 12 weeks prior to screening
- •A positive result in the alcohol and/or urine drug screen at the screening visit. Significant history of alcoholism or drug abuse as judged by the investigator or consuming more than 24 g alcohol per day for men, or more than 12 g alcohol per day for women.
- •Surgery or trauma with significant blood loss within the last 2 months prior to screening
- •Use of prescription or non-prescription medications known to cause QT prolongation
研究组 & 干预措施
dasiglucagon (ZP4207)
Repeated single fixed doses (s.c.injection) of dasiglucagon
干预措施: dasiglucagon (Drug)
GlucaGen
Repeated single fixed doses (s.c.injection) of GlucaGen
干预措施: GlucaGen (Drug)
结局指标
主要结局
Percentage of Patients With ADA
时间窗: 104 days after the first dose
Percentage of the combined results of treatment-induced ADA-positive patients and treatment-boosted ADA-positive patients out of the total number of evaluable patients. ADA = antidrug antibodies.
次要结局
- Percentage of Patients With Treatment-induced ADA(104 days after the first dose)
- Percentage of Patients With Treatment-boosted ADA(104 days after the first dose)
- Characterization of ADA Response - Cross-reactivity(104 days after the first dose)
- Characterization of ADA Response - Timing(104 days after the first dose)
- Characterization of ADA Response - Duration(104 days after the first dose)
- Characterization of ADA Response - Neutralizing Activity(104 days after the first dose)
- Characterization of ADA Response - Titer of Neutralizing Activity(104 days after the first dose)
- Pharmacokinetics - Area Under the Plasma Concentration Curve(0-90 minutes)
- Pharmacokinetics - Maximum Plasma Concentration(90 minutes)
- Pharmacokinetics - Time to Maximum Plasma Concentration(90 minutes)
- Pharmacodynamics - Area Under the Effect Curve(0-90 minutes)
- Pharmacodynamics - Change From Baseline Plasma Glucose(90 minutes)
- Pharmacodynamics - Time to Maximum Plasma Glucose Concentration(90 minutes)
- Pharmacodynamics - An Increase in the Plasma Glucose Concentration of ≥20 mg/dL Within 30 Minutes After Treatment(30 minutes)