Clinical trial NCT03171415: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Weight Loss
Overweight and Obesity
Keywords: Obesity
Overweight
Thermogenesis
Fat reduction
Lead sponsor: Raziel Therapeutics Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Spaulding Clinical Research LLC
First posted: 2017-05-31
Enrollment: 32
Sex: MALE
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a consecutive 4 cohort, dose escalation placebo-controlled clinical trial
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Adult male subjects, 20-60 years old.
2. Subject is considered overweight and obese, with 27.5 \< BMI ≤ 34.9.
3. Significant subcutaneous abdominal fat as defined by Waist to hip ratio (WHR) ≥ 0.9.
4. Subjects with stable weight in the last 3 months by medical history.
5. Not one of the following eating disorders by subject's declaration: anorexia nervosa, bulimia nervosa.
6. 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).
7. 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.
8. Subjects must be able to adhere to the visit schedule and protocol requirements and be available to complete the study.
9. Subjects must sign an informed consent indicating that they are aware of the investigational nature of the study.

Exclusion Criteria:

1. Subjects weighing less than 75 kg.
2. Subjects who have reduced/gained weight more than 5% of their current body weight in the last 3 months.
3. Unable to tolerate subcutaneous injection.
4. 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.
5. Subjects who test positive to either Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV) are not eligible.
6. Subjects with a clinical history of primary or secondary immunodeficiency, autoimmune disease or subjects taking immunosuppressive drugs such as corticosteroids are ineligible.
7. As a result of medical review, physical examination, the PI (or medically qualified nominee) considers the subject unfit for the study.
8. Medication use on regular basis.
9. Positive drug and alcohol tests.
10. Known sensitivity to components of the injection formulation.
11. Prior wound, tattoo or infection in the treated area.
12. Excessive growth of hair in the abdomen region.
13. Claustrophobia or MRI incompatible device or implant.

Primary outcomes:
measure: Safety: The Incidence of Treatment-related Adverse Events [AEs]
timeFrame: 0-168 days
measure: Efficacy: A Significant Thermogenesis at the Injected Site.
timeFrame: 28-168 days
Secondary outcomes:
measure: Duration of the Thermogenic Effect From Day 28.
timeFrame: 28-168 days
measure: Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen.
timeFrame: 28-168 days
measure: Changes in Fasting Blood Glucose From Baseline.
timeFrame: 56 days
measure: Changes in Blood Lipid Profile From Baseline.
timeFrame: 56 days
measure: Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
timeFrame: 1-2 days
measure: Changes in Body Weight
timeFrame: 56 days
measure: Changes in Waist to Hip Ratio [WHR]
timeFrame: 56 days
measure: Elucidation of the Histological Changes Account for the Thermogenic Effect.
timeFrame: 56 days
measure: Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling.
timeFrame: 28 days
measure: Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
timeFrame: 0.5, 1,2,3,4,5,6,8,12,16,24,30 hours
Other outcomes:
Locations:
city: West Bend
country: United States
facility: Spaulding Clinical
state: Wisconsin
Study officials:
References: