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

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.

• RZL-012 (Drug): small synthetic molecule for submental fat reduction
• Placebo (Drug): Placebo

Primary outcomes

• Number of Participants With Treatment-related Adverse Events [AEs] [12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase]: Safety

Secondary outcomes

• Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale [12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase]: 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
• Efficacy - Change in Satisfaction Score [12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase]: 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
• Efficacy - Relative Change in Measured Fat Volume [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]: 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
• Efficacy -Number of Participant With Correct Identification by Reviewers [12 weeks 12 weeks for the Double-Blind Phase]: 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
• Pharmacokinetics Measure - Drug Concentration in the Blood (ng/mL) [30 hours]: Measurement of maximum drug concentration (Cmax) (ng/mL) in the blood

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

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:

  1. 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
  2. is of nonchildbearing potential defined as clinically infertile as the result of surgical sterilization (hysterectomy, bilateral tubal ligation, and/or bilateral oophorectomy); or
  3. 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

Participant flow

Outcome results

• Number of Participants With Treatment-related Adverse Events [AEs] (Primary), Number, participants: RZL-012 50mg/ml 12; Placebo 12; RZL-012 Open Label 9
• Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale (Secondary), Number, flanks: RZL-012 50mg/ml Double Blind 7; Placebo Double Blind 0; RZL-012 Open Label Treatment 0
• Efficacy - Change in Satisfaction Score (Secondary), Count of participants, Participants: RZL-012 50mg/ml or Placebo 9
• Efficacy - Relative Change in Measured Fat Volume (Secondary), Mean, percentage of change from baseline.: RZL-012 50mg/ml Double Blind Part -37 +/- 55.2; Placebo Double Blind Part 33 +/- 41.4; RZL-012 Open Label Part -48.9 +/- 65.9
• Efficacy -Number of Participant With Correct Identification by Reviewers (Secondary), Count of participants, Participants: RZL-012 50mg/ml 5
• Pharmacokinetics Measure - Drug Concentration in the Blood (ng/mL) (Secondary), Mean, ng/ml: RZL-012 50mg/ml 961.8 +/- 273.4

Adverse events

Time frame: 12 weeks Double blind phase and 12 weeks open label phase

Other adverse events by term

• Study Protocol (PDF, 2022-05-30)
• Statistical Analysis Plan (PDF, 2022-06-01)