Evaluation the Effects of Various Treatments on RZL-012-Induced Adverse Events

An Open Label Phase 2 Study to Evaluate the Effects of a Local Anesthetic, Anti-inflammatory Medications and Compression Garments on RZL-012-Induced Adverse Events

This is a Phase 2, open-label, 2-stage, adaptive-design study in which subjects will be randomized into one of 5 treatment groups comprised of RZL-012 with or without additional study treatments:

Study Overview

• Status: Completed
• Conditions: Submental Fat
• Intervention / Treatment: Drug: RZL-012; Drug: RZL-012+Lidacaine injection prior treatment; Drug: RZL-012+Medrol; Drug: RZL-012+Celecoxib+Zyrtec; Drug: RZL-012+facial and neck wrap

Detailed Description

In the first stage of the study, 5 subjects will be randomized into each of the treatment groups. Study outcomes will be assessed up to one week thereafter to determine the need to modify additional study treatments. Subsequently up to 10 additional subjects will be randomized into each of the treatment groups for the second stage of the study.

For each subject, the study will consist of a screening period, baseline period in which subjects will receive a single treatment session of RZL-012 and a follow-up period. RZL-012 will be administered during a single treatment session via multiple injections into the submental area under the chin. Subjects will thereafter be monitored for safety and efficacy for at least 84 days.

Each subject will be treated with the same dose of RZL-012 :

• RZL-012 (concentration of injected solution 50 mg/mL RZL-012) of 7.5 mg/0.15 mL/injection point that results in a total dose/volume of 240±30mg mg/4.8±0.6 mL RZL-012, Each subject will receive additional study treatments in accordance with the treatment group to which the subject is randomized.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Manhattan, New York, United States, 10021
      • Luxurgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Is a male or female subject between the ages of 18 and 65 years, inclusive.
2. Has body mass index (BMI) between >22 kg/m2 and <40 kg/m2.
3. Has SMF bulge that is contiguous and fits to 32±4 injections sites according to a grid with 1 centimeter (cm) distance between injection points.
4. Has grade 3 to 4 of SMF as rated by both the C-CAT and S-CAT.
5. Has stable weight, with no fluctuation of >5 kg in the past 12 months.

6. 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 4 weeks after the last day of study drug and a negative serum pregnancy test (ß-hCG) at screening and negative urine pregnancy test at 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 and documented serum follicle-stimulating hormone (FSH) level > 40 mIU/mL or another documented medical condition (e.g., was born without a uterus)) NOTE: The following are considered highly effective contraceptive methods: hormonal oral contraceptives, injectables, and patches; intrauterine devices; double-barrier methods (synthetic condom, diaphragm, or cervical cap used with spermicidal foam, cream, or gel); and male partner sterilization.
7. If male (with or without vasectomy), agree to the use of highly effective contraceptive methods as listed above in criteria 7 as well as to use a barrier method, e.g. condom , from study check-in until 7 days after drug injection.
8. Is willing to avoid strenuous exercise for seven (7) days post treatment.
9. Is able to adhere to the visit schedule and protocol requirements and be available to complete the study.
10. 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:

1. Is unable to tolerate subcutaneous injections.
2. Has dysfunctional gallbladder activity (e.g., underwent cholecystectomy or cholecystitis).
3. Has any systemic disease including but not limited to gastritis or ulcers, renal dysfunction, hypertension, liver disease, glaucoma, diabetes and/or cardiovascular disease.
4. Has any contraindications to oral corticosteroids (prednisone), NSAIDs (e.g., Celecoxib) or non-sedative antihistamines (e.g. Zyrtec)
5. Has skin laxity (i.e., elastosis, skin crepiness, skin redundancy, skin draping, vertical and/or horizontal skin bands and folds, blunting of cervical mental angle, loss of opposition of skin to underlying neck structures due to skin laxity) that could obscure the evaluation and treatment of SMF.
6. Has any scars, unshaven hair, tattoos, facial hair or jewelry on or near the proposed treatment area.
7. Has presence of structures or confounding factors that may interfere with assessing SMF such as but not limited to enlarged submandibular salivary and/or parotid glands, micrognanthia, chin implant, soft tissue volume augmentation of chin and/or jawline, pronounced platysmal bands and deep necklace lines or presence of facial jowls that could obscure the evaluation of SMF.
8. Has a fat bulge under the chin that is too large to be adequately treated by 32±4 contiguous injections on a 1cm grid .
9. Has a fat bulge under the chin that is of an insufficient volume to allow 32±4 injections within a contiguous 1 cm grid.
10. 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.
11. Has an active bacterial, fungal, or viral infection in the proposed treatment area.
12. Has a pre-existing skin condition in the submental region that, at the Investigator's discretion, may confound evaluation or analysis.
13. Has previously had treatments or surgery in the submentum, such as but not limited to, focused ultrasound, radiofrequency, cryolipolysis, liposuction, sodium deoxycholate, or neck lift.
14. Has pre-existing neurological or gastrointestinal condition leading to dysphagia, dysphonia, or facial nerve palsy.
15. Has Dercum's Disease.
16. Has allergic reactions to injectables
17. Has allergic reactions to Zyrtec or Celecoxib.
18. Has any pre-existing medical condition other than increased SMF that, at the Investigator's discretion, may result in increased submental fullness, such as but not limited to, thyroid enlargement, goiter, cervical lymphadenopathy, etc.
19. Has a planned fat reduction procedure of any variety to the submental region for the duration of the study.
20. Has medication or a history of coagulopathy.
21. Has a history or family history of venous thrombotic disease.
22. Has been treated chronically at least three (3) months prior to study entry with systemic steroids or immunosuppressive drugs.
23. Has been treated chronically at least one (1) week prior to study entry with non-steroidal anti-inflammatory drugs (NSAIDs)
24. Has used anticoagulation therapies that may increase bleeding or bruising (i.e., aspirin, ibuprofen/Celecoxib, warfarin, vitamins, and herbal preparations) for seven (7) days prior to treatment.
25. .Has had treatment with botulinum toxin injections in the neck or chin area within nine (9) months prior to screening.
26. Current participation or participation within three (3) months prior to the start of this study in a drug or other investigational research study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: RZL-012 50mg/ml

Drug: RZL-012; 50mg/ml drug formulation; Drug: RZL-012+Lidacaine injection prior treatment; 5ml lidocaine will be injected 10 minutes before RZL-012 treatment; Drug: RZL-012+Medrol; oral Medrol dose pack (8 mg (2 tablets) on Day 1 before treatment followed by 16 mg after treatment (as per Instructions for Use)). From Day 2, a daily tapering off by 4 mg until Day 6 will be administered per Rx Instructions for use; Drug: RZL-012+Celecoxib+Zyrtec; 200 mg Celecoxib BID and 10 mg Zyrtec BID on Days 1, 2, 3, 4, 5 and 6; Drug: RZL-012+facial and neck wrap; Universal Facial Band

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Adverse Events Follow up	Number of subjects with severe swelling in each subgroup	84 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy -Reduction in Score According to Clinician Chin Assessment Tool (C-CAT)	Number of subjects who has at least 1 grade improvement in C-CAT. The CAT is composed of 5 points where 0 represents no fat and 4 represent very noticeable bulge and fat that extends beyond the neck	84 days
Efficacy - Number of Participants With 1 Grade Improvement According to the Subject Chin Assessment Tool (S-CAT)	To determine the efficacy of RZL-012 vs. RZL-012 with additional treatments on Day 84 versus baseline using the Subject Chin Assessment Tool (S-CAT). The CAT is composed of 5 points where 0 represents no fat and 4 represent very noticeable bulge and fat that extends beyond the neck	84 days
Efficacy - Percentage of Change From Baseline in Submental Fat Volume	Percentage of change from baseline in submental fat volume , as measured with MRI in RZL-012 vs. RZL+other treatments treated subjects vs. placebo treated subjects on Day 84 following injection.	84 days

Collaborators and Investigators

• Sponsor: Raziel Therapeutics Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2022
• Primary Completion (Actual): June 12, 2023
• Study Completion (Actual): June 12, 2023

Study Registration Dates

• First Submitted: July 25, 2022
• First Submitted That Met QC Criteria: July 25, 2022
• First Posted (Actual): July 27, 2022

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: RZL-012-SMF-SWMTG-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No