A Double Blind, Randomized, Placebo Controlled, Dose Escalation Phase 2a Clinical Trial for the Evaluation of Safety, Efficacy and Thermogenesis-induction of RZL-012 in Overweight and Obese Volunteers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Safety: The Incidence of Treatment-related Adverse Events [AEs]
研究概览
简要总结
Obesity is a direct result of food-intake in excess of body energy expenditure. Thus, induction of increased energy expenditure via the activation of thermogenesis at targeted anatomical sites can counterbalance obesity. This trial aims to study RZL-012, a novel compound, in treating obesity by activating thermogenesis in subcutaneous fat.
详细描述
Obesity is a direct result of food-intake in excess of body energy expenditure. Therefore, a feasible approach to combat obesity is via energy-consuming activities, such as physical exercise. Unfortunately, our modern society is moving in the other direction, spending more time in immobilized positions, at work and at home. An alternative strategy for the induction of increased energy expenditure is via the activation of thermogenic cells that utilize fat to produce heat.RZL-012 is a novel molecule that enables de-novo generation of thermogenic tissue at favorable anatomical sites. As a result, the extra fat accumulated in obese persons will be turned into heat. This is a double blind, randomized, placebo controlled, dose escalation Phase 2a clinical trial for the evaluation of safety, efficacy and thermogenesis-induction of RZL-012 in overweight and obese volunteers. This trial aims to study the ability of RZL-012 in treating obesity via the induction of thermogenic foci in subcutaneous fat.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double Blind, Randomized, Placebo Controlled
入排标准
- 年龄范围
- 20 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Adult male subjects, 20-60 years old.
- •Subject is considered overweight and obese, with 27.5 < BMI ≤ 34.
- •Significant subcutaneous abdominal fat as defined by Waist to hip ratio (WHR) ≥ 0.
- •Subjects with stable weight in the last 3 months by medical history.
- •Not one of the following eating disorders by subject's declaration: anorexia nervosa, bulimia nervosa.
- •Generally considered healthy according to medical history, physical examination, electrocardiogram (ECG) and laboratory evaluation with a special emphasis on metabolic parameters (fasting glucose concentration < 100 mg, normal blood pressure).
- •Subject is willing to refrain from sexual activity or agrees to use a double-barrier contraceptive device (e.g., condom and spermicide) for 4 weeks after treatment with RZL
- •Subjects must be able to adhere to the visit schedule and protocol requirements and be available to complete the study.
- •Subjects must sign an informed consent indicating that they are aware of the investigational nature of the study.
排除标准
- •Subjects weighing less than 75 kg.
- •Subjects who have reduced/gained weight more than 5% of their current body weight in the last 3 months.
- •Unable to tolerate subcutaneous injection.
- •Subjects with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric disorders, that in the opinion of the investigator put the subject at significant risk, are not eligible.
- •Subjects who test positive to either Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV) are not eligible.
- •Subjects with a clinical history of primary or secondary immunodeficiency, autoimmune disease or subjects taking immunosuppressive drugs such as corticosteroids are ineligible.
- •As a result of medical review, physical examination, the PI (or medically qualified nominee) considers the subject unfit for the study.
- •Medication use on regular basis.
- •Positive drug and alcohol tests.
- •Known sensitivity to components of the injection formulation.
- •Prior wound, tattoo or infection in the treated area.
- •Excessive growth of hair in the abdomen region.
- •Claustrophobia or MRI incompatible device or implant.
研究组 & 干预措施
RZL-012
A single-time injection, multiple subcutaneous injections of RZL-012 administered into 8-36 sites (0.1mL per site):
- 40mg RZL-012 -administered at 8 sites
- 80mg RZL-012 - administered at 16 sites
- 120mg RZL-012 - administered at 24 sites
- 180mg RZL-012 - administered at 36 sited
干预措施: RZL-012 (Drug)
Placebo
A single-time injection, multiple subcutaneous injections of Placebo administered into 8-36 sites (0.1mL per site)
干预措施: Placebo (Drug)
结局指标
主要结局
Safety: The Incidence of Treatment-related Adverse Events [AEs]
时间窗: 0-168 days
AEs will be assessed by significant clinical changes in safety parameter (e.g. vital signs, ECG, clinical laboratory evaluations)AEs incidence will be by body system, seriousness, severity and relation to study drug by cohort.
Efficacy: A Significant Thermogenesis at the Injected Site.
时间窗: 28-168 days
Thermogenesis is measured by thermal imaging is non-invasive, non-radiating Infra-Red thermal camera that passively measures the emitting infra-red radiation of body surface. Difference in temperatures between the sites (treated - not treated) by visit treatment along with the change from baseline (net-delta) in these differences by cohort and overall. Significant thermogenesis is defined as net-delta ≥ 1. Outcome measure data table represents the number of subjects who demonstrated an increase that is higher than 1 celsius degree.
次要结局
- Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.(0.5, 1,2,3,4,5,6,8,12,16,24,30 hours)
- Changes in Body Weight(56 days)
- Changes in Waist to Hip Ratio [WHR](56 days)
- Elucidation of the Histological Changes Account for the Thermogenic Effect.(56 days)
- Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling.(28 days)
- Changes in Blood Lipid Profile From Baseline.(56 days)
- Duration of the Thermogenic Effect From Day 28.(28-168 days)
- Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen.(28-168 days)
- Changes in Fasting Blood Glucose From Baseline.(56 days)