A Single Blind, Randomized, Placebo-controlled, Phase 2a, 2-cohort Study for the Evaluation of Safety and Efficacy of RZL-012 for Submental Fat Reduction in Healthy Volunteers.

Study Overview
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Brief Summary
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Twenty-Eight (28) subjects (12 for cohort 1 and 16 for cohort 2 ) will be included in the study. Subjects in each cohort will be injected with a different dose of RZL-012. The total of 28 subjects will be enrolled in 2 clinical sites.

Detailed Description
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This is a single blinded, randomized, placebo-controlled, 2-cohort clinical study in healthy volunteers. Cohort 1 will be comprised of 8 active (RZL-012) and 4 placebo subjects. Cohort 2 will be comprised of 16 subjects wuth at least 4 placebo subjects. All subjects will receive a single dose of RZL-012 or vehicle into the submental area, after which they will be monitored for safety and efficacy during 84 days of follow-up. Subjects will be blinded to study treatment while physicians will not be blinded. The study will be composed of 2 treatment cohorts, 12 in cohort 1 and 16 in cohort 2. The study will be conducted in 2 clinical sites. Per each study cohort, subjects will be randomized to receive active or placebo treatment according to a randomization program that will be prepared prior to study initiation. Each clinical site will have at least one active and one placebo treatment subject per each study cohorts. In case of slow enrollment in one of the sites, other sites may complete the enrollment of subjects in each cohort. Cohort 1 (N=12) - Each subject will be dosed with up to 120 mg RZL-012 (depending on submental fat area) or vehicle. Cohort 2 (N=16) - Each subject will be dosed with up to 240 mg RZL-012 (depending on submental fat area) or vehicle. Treatment of cohort 2 will start following cohort 1 day 28 data. An independent Data Safety Monitoring Board (DSMB) will review safety and tolerability data for cohort 1 subjects, 28 days after injection, and decide whether it is safe to increase the dose for the next study cohort. The decision to proceed to the cohort 2 will be made within 30 days (28 days + 2 days) after injection of the last dosed subject in cohort 1. The DSMB will be comprised of two independent MDs with expertise in the aesthetic area and in conduction of clinical trials. In case of serious safety concerns (e.g. prolonged severe swelling or severe pain following injection) among cohort 1 subjects receiving the 120mg dose, sponsor and DSMB may decide to reduce or stay with the 120mg/subject dose level for cohort 2 subjects.

Official Title
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A Single Blind, Randomized, Placebo-controlled, Phase 2a, 2-cohort Study for the Evaluation of Safety and Efficacy of RZL-012 for Submental Fat Reduction in Healthy Volunteers.

Conditions
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Submental Fat

Intervention / Treatment
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* Drug: RZL-012
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women 18-65 years old. Subjects with Body Mass Index <35 Subjects must have submental skin fold thickness greater than 1.5 cm as measured with calipers. Males must be willing to be clean shaved for all study visits. Patient weight must be stable (no fluctuation of >15 pounds in the past year) Males or females in the age of fertility agree 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 IRB approved informed consent indicating they are aware of the investigational nature of the study. Exclusion Criteria: Subjects meeting any of the following criteria will be excluded from study participation: Unable to tolerate subcutaneous injection. Pregnant or lactating women. Subjects with dysfunctional gallbladder activity, e.g. underwent cholecystectomy or cholecystitis. Any uncontrolled systemic disease -a potential patient in whom therapy for a systemic disease is not yet stabilized will not be considered for entry into the study Treatment with botulinum toxin injections in the neck or chin area within 6 months before screening. Excessive submental skin laxity. Any Scars, unshaven hair, tattoos or jewelry on or near the proposed treatment area Significant history or current evidence of a medical, psychological or other disorder that, in the investigator's opinion, would preclude enrollment into the study An active dermatitis or open wound in the proposed treatment area An active bacterial, fungal, or viral infection in the proposed treatment area Pre-existing skin condition in the submental region that may confound evaluation or analysis, at investigator discretion Previously treated with focused ultrasound, radiofrequency, cryolipolysis, liposuction, sodium deoxycholate to the submental region within the previous 6 months Pre-existing neurological or gastrointestinal condition leading to dysphagia, dysphonia or facial nerve palsy Pre-existing medical condition other than increased submental fat that may result in increased submental fullness such as but not limited to thyroid enlargement, goiter, cervical lymphadenopathy etc., at investigator discretion Must not have a planned fat reduction procedure of any variety to the submental region for the duration of the study Must not have planned significant alterations in diet or physical activity that may result in significant fluctuations in weight. Subjects with medication or history of coagulopathy. Allergic subjects to Bendaryl. Subjects treated chronically at least 3 months prior to study entry with systemic steroids or immunosuppressive drugs. Subjects treated chronically at least one week prior to study entry with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Current participation or participation within 3 months prior to the start of this study in a drug or other investigational research study. Claustrophobia or MRI incompatible device or implant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RZL-012<br>A single-treatment injection, multiple subcutaneous injections of RZL-012 administered into 48 sites in the submental fat (0.05/0.1mL per site): Up to 120mg administered at 48 sites in a volume of 0.05 ml at each injection site (total injected volume 2.4mL) Up to 240 mg administered at 48 sites in a volume of 1 ml at each injection site (total volume injected 4.8mL) | Drug: RZL-012<br>* Subcutaneous injection to the submental fat area<br>|
| Placebo Comparator: Vehicle<br>Subject receive a single-treatment injection. Multiple injections of the Placebo are administered at 48 sites (0.05/0.1mL per site) into the submental fat. Up to a total of 2.4 mL will be injected for placebo subjects enrolled during cohort 1. Up to a total of 4.8 mL will be injected for placebo subjects enrolled during cohort 2. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Adverse Events Follow up | To evaluate the safety of RZL-012 subcutaneous injections in the submental area, relative to placebo, as assessed by spontaneous adverse event reports and post injection evaluation of subjects. Specifically, Pain, Induration, Bruising, Erythema and Edema will be closely followed up following treatment. | 0-84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physician's Global Assessment | Evaluation of treatment efficacy by using Physician's global assessment questionnaire for active vs. placebo subjects, on study Day 84 | 0-84 days | 
| Efficacy: MRI Volume Reduction | Reduction from baseline in submental fat volume, as measured with MRI, in RZL-012 treated subjects vs. placebo treated subjects on Day 84 following injection. | 0-84 days | 
| Efficacy: Improvement in Face Satisfaction Questionnaire - A Score From 0 (Worst) to 100 (Best) Marks the Subject's Satisfaction | Improvement from baseline in the Faceq satisfaction questionnaire rating score in RZL-012 treated subjects vs. placebo treated subjects on day 84. | 0-84 days |