Back to resultsEvaluation of Safety, Efficacy and Thermogenesis-induction of RZL-012 in Overweight and Obese Volunteers
Primary Purpose
Obesity, Weight Loss, Overweight and Obesity
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
RZL-012
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Obesity focused on measuring Obesity, Overweight, Thermogenesis, Fat reduction
Eligibility Criteria
Inclusion Criteria:
- Adult male subjects, 20-60 years old.
- Subject is considered overweight and obese, with 27.5 < BMI ≤ 34.9.
- Significant subcutaneous abdominal fat as defined by Waist to hip ratio (WHR) ≥ 0.9.
- 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 012.
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- Spaulding Clinical
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
RZL-012
Placebo
Arm Description
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
A single-time injection, multiple subcutaneous injections of Placebo administered into 8-36 sites (0.1mL per site)
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
Changes in Fasting Blood Glucose From Baseline.
Changes from baseline in fasting blood glucose by visit, treatment, and cohort.
Changes in Blood Lipid Profile From Baseline.
Changes from baseline in lipid profile by visit, treatment, and cohort.
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Averaged Cmax values by cohort.
Changes in Body Weight
Changes from baseline in body weight by visit, treatment, and cohort.
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.
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.
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.
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Averaged Tmax values by cohort.
Full Information
NCT ID
NCT03171415
First Posted
May 24, 2017
Last Updated
August 8, 2019
Sponsor
Raziel Therapeutics Ltd.
Collaborators
Spaulding Clinical Research LLC
1. Study Identification
Unique Protocol Identification Number
NCT03171415
Brief Title
Evaluation of Safety, Efficacy and Thermogenesis-induction of RZL-012 in Overweight and Obese Volunteers
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
July 25, 2017 (Actual)
Primary Completion Date
December 28, 2018 (Actual)
Study Completion Date
December 28, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Raziel Therapeutics Ltd.
Collaborators
Spaulding Clinical Research LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Weight Loss, Overweight and Obesity
Keywords
Obesity, Overweight, Thermogenesis, Fat reduction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
This is a consecutive 4 cohort, dose escalation placebo-controlled clinical trial
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double Blind, Randomized, Placebo Controlled
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RZL-012
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A single-time injection, multiple subcutaneous injections of Placebo administered into 8-36 sites (0.1mL per site)
Intervention Type
Drug
Intervention Name(s)
RZL-012
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety: The Incidence of Treatment-related Adverse Events [AEs]
Description
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
Title
Efficacy: A Significant Thermogenesis at the Injected Site.
Description
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
Secondary Outcome Measure Information:
Title
Duration of the Thermogenic Effect From Day 28.
Description
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
Title
Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen.
Description
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
Title
Changes in Fasting Blood Glucose From Baseline.
Description
Changes from baseline in fasting blood glucose by visit, treatment, and cohort.
Time Frame
56 days
Title
Changes in Blood Lipid Profile From Baseline.
Description
Changes from baseline in lipid profile by visit, treatment, and cohort.
Time Frame
56 days
Title
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Description
Averaged Cmax values by cohort.
Time Frame
1-2 days
Title
Changes in Body Weight
Description
Changes from baseline in body weight by visit, treatment, and cohort.
Time Frame
56 days
Title
Changes in Waist to Hip Ratio [WHR]
Description
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
Title
Elucidation of the Histological Changes Account for the Thermogenic Effect.
Description
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
Title
Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling.
Description
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
Title
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Description
Averaged Tmax values by cohort.
Time Frame
0.5, 1,2,3,4,5,6,8,12,16,24,30 hours
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Adult male subjects, 20-60 years old.
Subject is considered overweight and obese, with 27.5 < BMI ≤ 34.9.
Significant subcutaneous abdominal fat as defined by Waist to hip ratio (WHR) ≥ 0.9.
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 012.
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.
Exclusion Criteria:
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.
Facility Information:
Facility Name
Spaulding Clinical
City
West Bend
State/Province
Wisconsin
ZIP/Postal Code
53095
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Evaluation of Safety, Efficacy and Thermogenesis-induction of RZL-012 in Overweight and Obese Volunteers
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