A Randomized, Investigator and Participant Blinded, Placebo Controlled, Multiple Ascending Dose, Two Part Design Study to Assess the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of MHS552 in Adults With Type 1 Diabetes Mellitus (T1DM)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)
研究概览
简要总结
The purpose of this two-part multiple ascending dose study is to evaluate the safety and tolerability of multiple doses of MHS552 in adults with type 1 diabetes mellitus. Participants will be treated for 4 or 12 weeks followed by an 8 week follow-up period
详细描述
This is a Phase 1b, randomized, investigator and participant blinded, placebo controlled, multiple ascending dose (MAD) study in adults with type 1 diabetes mellitus (adults aged 18-45 years, inclusive, diagnosed with T1DM within 5 years at the time of screening). This MAD study will be conducted in two sequential parts, Part A and Part B.
In Part A, after an screening period of up to 28 days, participants will be randomized (in a 3:1 ratio) to MHS552 or placebo administered subcutaneously (s.c.) weekly for four weeks of treatment. Part A will consist of up to 3 cohorts (low, medium, high dose), with approximately 4-8 participants completing each cohort (total of approximately 16 participants). Participants will be followed-up during 8 weeks post last dose. The total duration of study participation of Part A is approximately 106 Days.
In Part B, after a screening period of up to 28 days, approximately 12 participants will be randomized (in a 2:1 ratio) to MHS552 or placebo administered s.c. weekly for 12 weeks of treatment (dose level 4). Participants will be followed-up during 8 weeks post last dose with End of Study (EoS) visit at Day 134. The total duration of study participation of Part B is approximately 162 Days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult men and women ages 18 to 45, inclusive, body weight between ≥40 to ≤150 kg, inclusive, with T1DM, a maximum of 5 years from T1DM diagnosis at screening.
- •Evidence of one or more T1DM autoantibody(ies) including glutamic acid decarboxylase (anti GAD), protein tyrosine, phosphatase-like protein (anti-IA-2); zinc transporter 8 (anti-ZnT8); islet cell (cytoplasmic) (anti-ICA)
- •Residual pancreatic β-cell function (fasting C-peptide >100 pmol/L [0.30 ng/mL] or random C peptide >200 pmol/L [0.60 ng/mL])
排除标准
- •History of hypersensitivity to drugs of similar biological class, IL-2 protein analogues, or immunoglobulin (IgG1) proteins, hypersensitivity to any components of the study drug, or history of severe hypersensitivity reaction or anaphylaxis to biological agents, e.g. human monoclonal antibody.
- •Use of other investigational drugs or use of immunosuppressive agents at the time of enrollment, or within 5 half-lives of enrollment, or until the expected PD effect has returned to baseline, whichever is longer; or longer if required by local regulations.
- •Diabetes forms other than autoimmune type 1 such as maturity-onset diabetes of the young (MODY), latent autoimmune diabetes of the adult (LADA), acquired diabetes (secondary to medications or surgery), type 2 diabetes by judgement of the investigator.
- •Diabetic ketoacidosis within 2 weeks.
- •Polyglandular auto-immune disease, including but not limited to: Addison's disease, pernicious anemia, celiac sprue and psoriasis. Treated, stable Hashimoto's thyroiditis is not exclusionary.
- •History of capillary leak syndrome (CLS).
- •Ongoing, and up to 2 weeks prior to screening, initiation of medications or change in dose of medications that may affect glucose control (e.g, systemic steroids, thiazides, beta blockers).
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Part A: Cohort 1 - MHS552 low dose
Participants will receive MHS552 low dose once weekly subcutaneously for 4 weeks
干预措施: MHS552 (Drug)
Part A: Cohort 1, 2, 3 - Placebo
Participants will receive placebo once weekly subcutaneously for 4 weeks
干预措施: Placebo (Drug)
Part A: Cohort 2 - MHS552 medium dose
Participants will receive MHS552 medium dose once weekly subcutaneously for 4 weeks
干预措施: MHS552 (Drug)
Part A: Cohort 3 - MHS552 high dose
Participants will receive MHS552 high dose once weekly subcutaneously for 4 weeks
干预措施: MHS552 (Drug)
Part B: MHS552
Participants will MHS552 (dose to be determined) once weekly subcutaneously for 12 weeks
干预措施: MHS552 (Drug)
Part B: Placebo
Participants will receive placebo once weekly subcutaneously for 12 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)
时间窗: Part A: up to 12 weeks; Part B: up to 20 weeks
Numbers of participants with AEs and SAEs including vital signs, electrocardiograms (ECG) and laboratory results
次要结局
- Area Under Plasma Concentration-time Curve calculated to the end of a dosing interval (AUCtau) for MHS552(Part A: up to Day 78; Part B: up to Day 134)
- Maximum ObservBlood Concentrations (Cmax) for MHS552(Part A: up to Day 78; Part B: up to Day 134)
- Time to Reach Maximum Blood Concentrations (Tmax) of MHS552(Part A: up to Day 78; Part B: up to Day 134)