A Randomized, Subject- and Investigator-blinded, Placebo Controlled Study to Assess the Safety, Pharmacokinetics and Efficacy of Intravenous Bimagrumab in Overweight and Obese Patients With Type 2 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 48
研究概览
简要总结
This study assessed the safety, pharmacokinetics and efficacy of bimagrumab when administered in overweight and obese patients with type 2 diabetes
详细描述
A non-confirmatory, randomized, subject and investigator blinded, placebo controlled, parallel-arm study, investigating a 48-week treatment period with i.v. bimagrumab 10 mg/kg in overweight and obese subjects with type 2 diabetes.
Participants were randomized and assigned to one of the following 2 treatment arms in a ratio of 1:1:
Arm 1: Bimagrumab 10 mg/kg up to maximum 1200 mg, every 4 weeks (12 doses) until week 44.
Arm 2: Placebo, every 4 weeks (12 doses) until week 44.
The study consisted of a screening baseline period of 3 weeks, treatment period of 48 weeks and then a follow-up period of 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes with HbA1c between 6.5% and 10% at screening with stable treatment for 3 months prior to randomization
- •On one of the following anti-diabetes regimens with stable treatment for approximately 3 months prior to randomization: 1) metformin monotherapy; 2) DPP4 inhibitor agent monotherapy; 3) combination therapy of metformin and DPP4 inhibitor agent; 4) no anti-diabetes therapy.
- •Body Mass Index of 28 to 40 kg/m2 at screening
- •Body weight between 65 and 140 kg at screening
排除标准
- •Women of child-bearing potential unless they are using highly effective methods of contraception
- •Diabetes other than Type 2 such as Type 1 diabetes, surgically induced diabetes, "brittle" type 2 diabetes as per investigator judgement, history of severe hypoglycemic episodes in the year preceding screening or hypoglycemic unawareness
- •History of clinically significant arrythmias, heart failure, unstable angina, myocardial infarction or stroke, coronary artery bypass graft surgery, or percutaneous coronary intervention, deep vein thrombosis/pulmonary embolism, valve disorders or defects, pulmonary hypertension within 6 months of screening or 1 year for drug-eluting stents
- •Tachycardia
- •Use of anti-obesity medications, nutritional supplements or over the counter products for weight loss within 3 months of screening
- •Use of medications known to induce weight gain such as some anti-convulsant and psychotropic medications within 3 months of screening
- •Any chronic active infection (e.g., HIV, Hepatitis B or C, tuberculosis, etc) or has received anti-HCV treatments within the previous 6 months.
- •Uncontrolled thyroid disease. Stable euthyroid patients on stable thyroid replacement therapy for at least 3 months of screening are allowed.
- •Abnormal liver function tests such as SGOT, SGPT, alkaline phosphatase, or serum bilirubin, or abnormal lipase and/or amylase.
- •Known history or presence of severe active acute or chronic liver disease (e.g., cirrhosis).
- •Uncontrolled depression
- •Use of skeletal muscle anabolic agents in any form for 3 months prior to screening
- •Chronic kidney disease [estimated glomerular filtration rate (GFR) < 30 mL/min];
研究组 & 干预措施
BYM338 10 mg/kg
Bimagrumab (BYM338) 10 mg/kg up to maximum 1200 mg, every 4 weeks until week 44 (12 doses)
干预措施: BYM338 10 mg/kg (Drug)
Placebo
Placebo, every 4 weeks until week 44 (12 doses)
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 48
时间窗: Baseline, Week 48
Dual energy X-ray absorptiometry (DXA) was used to assess changes in body composition, including total fat and lean body mass (FM and LBM) and appendicular skeletal fat and muscle mass (aFM and aLBM). DXA instruments had a source that generated x-rays split into two energies which measured bone mineral mass and soft tissue from which fat and fat-free mass (or lean body mass) were estimated.
次要结局
- Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 24(Baseline, Week 24)
- Time to Reach the Maximum Concentration After Drug Administration (Tmax) Derived on Day 168 and 308(Day 1, 168, 308 at pre-dose and 45 mins post-dose)
- Change From Baseline in Weight(Baseline, Week 24, Week 48)
- Change From Baseline in HbA1c at Week 24 and 48(Baseline, Week 24, Week 48)
- The Trough Observed Analyte Concentration (Ctrough) of Repeat Doses of BYM338 10 mg/kg on Day 84, 168, 252, 308 and 336(Day 84, 252, 336 at pre-dose only. Day 168, 308 at pre-dose and 45 mins post-dose)
- Change From Baseline in Lean Body Mass (LBM) Measured by DXA(Baseline, Week 24, Week 48)
- Change From Baseline in Insulin Resistance (HOMA2-IR)(Baseline. Week 12, Week 36)
- Maximum Observed Serum Concentration(Cmax) Derived on Day 1, 168 and 308(Day 1, 168, 308 at pre-dose and 45 mins post-dose)
- Change From Baseline in Body Mass Index (BMI)(Baseline, Week 24, Week 48)
- Change From Baseline in Waist to Hip Ratio(Baseline, Week 24, Week 52)
- Change From Baseline in Waist Circumference(Baseline, Week 24, Week 52)
- Immunogenicity Assessed by the Number of Participants Developing Anti-BYM338 Antibodies During the Trial(392 days)