Evaluation of Safety and Efficacy of RZL-012 in Subjects Seeking Fat Reduction in the Flanks

Study Overview
=================
Brief Summary
-----------------
A total of 12 subjects will be injected with RZL-012 and placebo. Each of the subject's flanks will be randomized for each of the treatment. A total of 24 flanks will be randomized in the double blind phase. They will be monitored for safety and efficacy for 12 weeks. After codes opening, a second treatment cycle on the previously untreated contralateral flank will be done. Subjects will be monitored for safety and efficacy for additional 12 weeks.

Detailed Description
-----------------
This clinical trial is comprised of a double-blind, placebo-controlled phase followed by an open-label phase. The double-blind, placebo-controlled phase of the trial will consist of a screening period, baseline visit and a 12-week post-treatment follow-up period. At the baseline visit, each flank (right and left) of each study participant will be randomized into either the active RZL-012 treatment group or the placebo group and each flank will receive multiple injections in a single session of RZL-012 or placebo. Blood samples will be collected for 6 of the 12 subjects for PK analyses. All subjects will be followed up for 12 weeks after the single treatment session. Upon completion of the double-blind phase of the study, and the opening of codes subjects will be offered RZL-012 open-label treatment in the flank previously treated with placebo. Consenting subjects will be followed for safety and efficacy for an additional 12 weeks. In both the double-blind and open-label phases of the study, subjects will be monitored for adverse events (AEs). Subjects will return to the site for visits at 1 week, 4 weeks, 8 weeks, and 12 weeks post treatment and will be monitored for safety and efficacy during these visits. Subjects who will be collected with PK will return to the clinic at Day 1 post injection for further PK samples. The dimensions of flanks will be measured using 3D images and volumetric calculations using Canfield 3D images.

Official Title
-----------------
A Double-Blind, Placebo-Controlled Phase Followed by An Open-Label Phase to Evaluate the Safety and Efficacy of RZL-012 in Subjects Seeking Fat Reduction in the Flanks

Conditions
-----------------
Flank Mass

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Is a male or female subject between the ages of 18 and 65 years, inclusive. Has body mass index (BMI) BMI of ≥ 22 and < 30. Has clearly visible and palpable fat in the flanks Has symmetrical appearance of right and left flanks Agrees to maintain weight (i.e., within 5% of body weight) by not making any changes in diet. Agree to avoid exposure of the treated area to the sun for at least 1 month after each treatment session. If female, is not pregnant or breastfeeding based on the following: agree to the use of highly effective contraceptive methods for at least 2 weeks before baseline until 28 days after the last day of study drug and a negative urine pregnancy test at screening and baseline; or is of nonchildbearing potential defined as clinically infertile as the result of surgical sterilization (hysterectomy, bilateral tubal ligation, and/or bilateral oophorectomy); or is confirmed postmenopausal status (defined as either having amenorrhea for ≥ 12 consecutive months without another cause, having documented serum follicle-stimulating hormone (FSH) level > 40 mIU/mL, or having another documented medical condition (e.g., was born without a uterus)) If male (with or without vasectomy), agree to the use of highly effective contraceptive methods, e.g. condom, from study baseline until 7 days after the last day of study drug. Is willing to avoid strenuous exercise for seven (7) days post treatment. Is motivated to adhere to the visit schedule and protocol requirements. Is willing and able to sign an Institutional Review Board (IRB) approved informed consent form (ICF) indicating that they are aware of the investigational nature of the study. Exclusion Criteria: Is unable to tolerate subcutaneous injections. Has dysfunctional gallbladder activity (e.g., underwent cholecystectomy or cholecystitis). Has an uncontrolled systemic disease that is not stabilized (i.e., cardiovascular disease, mental illness). Has used anticoagulation therapies that may increase bleeding or bruising (i.e., aspirin, ibuprofen, vitamins, and herbal preparations) for seven (7) days prior to treatment. Has medication or a history of coagulopathy. Has a history or family history of venous thrombotic disease. Had a non-invasive fat reduction and/or body contouring procedure in the flanks within the past 12 months. Has any scars, unshaven hair, tattoos, on or near the proposed treatment area. Has significant history or current evidence of a medical, psychological or other disorder that, in the Investigator's opinion, would preclude enrollment in the study. Has an active dermatitis or open wound in the proposed treatment area. Abnormal coagulation profile including: activated partial thromboplastin time (aPTT) > ULN, international normalized ratio (INR) > ULN reference range (> 1.3), prothrombin time (PT) > ULN. Has an active bacterial, fungal, or viral infection in the proposed treatment area. Has known allergic reactions to any injectables. Has been treated chronically in the past 3 months prior to study entry with systemic steroids or immunosuppressive drugs. Has been treated chronically at least one (1) week prior to study entry with non-steroidal anti-inflammatory drugs (NSAIDs). Current participation or participation within three (3) months prior to the start of this study in a drug or other investigational research study

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Each of the subject's flanks will be randomized for RZL-012 and placebo injections.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RZL-012 50mg/ml<br>Subjects flanks treated with RZL-012 (in the double blind phase) will undergo a single treatment session with 50-55 injections. The maximal number of injections will be 55 with maximal doses 412.5 mg. Each injection point will be dosed with 7.5 mg for in a volume of 0.15 mL/injection site. | Drug: RZL-012<br>* small synthetic molecule for submental fat reduction<br>|
| Placebo Comparator: Placebo<br>Subjects flanks treated with placebo (in the double blind phase) will undergo a single treatment session with 50-55 injections. The maximal number of injections will be 55 with maximal volume of 8.25mL. Each injection point will be dosed with 0.15 mL/injection site. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-related Adverse Events [AEs] | Safety | 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | To compare the proportion of flanks having an improvement as indicated by reduction in score from 6 to 0 according to the Physician Global Assessment Scale (GAIS) in RZL-01-treated flanks vs placebo-treated flanks | 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase | 
| Efficacy - Change in Satisfaction Score | To compare the proportion of subjects who are satisfied with treatment results as indicated by a binary yes/no satisfaction questionnaire in RZL-012-treated flanks vs placebo-treated flanks | 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase | 
| Efficacy - Relative Change in Measured Fat Volume | Measure the relative mean reduction in volume (%) at post treatment vs. baseline for each of the treated flanks, as measured by 3D images using the Canfield 3D system in RZL-012-treated flanks vs placebo-treated flanks at 12 weeks vs. baseline | 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase. Baseline for the open-label phase considered to be 12 weeks after double blind treatment | 
| Efficacy -Number of Participant With Correct Identification by Reviewers | Blinded reviewers will identify, per patient, the flank treated with test compound (active) vs the flank treated with Placebo. Success will be defined as at least 70% correct identification vs the expected 50% correct identification based on random guessing | 12 weeks 12 weeks for the Double-Blind Phase | 
| Pharmacokinetics Measure - Drug Concentration in the Blood (ng/mL) | Measurement of maximum drug concentration (Cmax) (ng/mL) in the blood | 30 hours |