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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
32
Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 8-36 sites (0.1mL per site) into the abdominal subcutaneous fat.
Subject receive a single-time injection. Multiple injections of the Placebo are administered at 8-36 sites (0.1mL per site) into the abdominal subcutaneous fat.
Spaulding Clinical
West Bend, Wisconsin, United States
Safety: The Incidence of Treatment-related Adverse Events [AEs]
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.
Time frame: 0-168 days
Efficacy: A Significant Thermogenesis at the Injected Site.
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.
Time frame: 28-168 days
Duration of the Thermogenic Effect From Day 28.
The duration of the thermogenic effect for subjects in the active arm with thermogenic effect (net-delta ≥ 1) by visit and cohort.
Time frame: 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.
Subcutaneous Fat Mass (SFM) ratio (treated sites / control sites) averaged over the MRI slices by visit, treatment and cohort and the change from baseline in SFM ratio (in % from the ratio at baseline) compared between the treatment arms.
Time frame: 28-168 days
Changes in Fasting Blood Glucose From Baseline.
Changes from baseline in fasting blood glucose by visit, treatment, and cohort.
Time frame: 56 days
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Changes in Blood Lipid Profile From Baseline.
Changes from baseline in lipid profile by visit, treatment, and cohort.
Time frame: 56 days
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Averaged Cmax values by cohort.
Time frame: 1-2 days
Changes in Body Weight
Changes from baseline in body weight by visit, treatment, and cohort.
Time frame: 56 days
Changes in Waist to Hip Ratio [WHR]
Changes from baseline in WHR by visit, treatment, and cohort. WHR is calculated by measurements of waist circumference and hip circumference.
Time frame: 56 days
Elucidation of the Histological Changes Account for the Thermogenic Effect.
An abdominal subcutaneous adipose tissue biopsy will be taken from the injected side. Histology results will be assessed for 2 subjects who were injected with 120 mg RZL-012 and for one subject who was injected with placebo.
Time frame: 56 days
Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling.
Changes from baseline in inflammatory markers and cytokines by visit, treatment, and cohort. Testing of inflammatory markers and cytokines will be conducted by blood sampling.
Time frame: 28 days
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Averaged Tmax values by cohort.
Time frame: 0.5, 1,2,3,4,5,6,8,12,16,24,30 hours