Efficacy and Safety of RZL-012 on Submental Fat Reduction

• ClinicalTrials.gov Identifier: NCT04867434
• Recruitment Status: Recruiting
• First Posted: April 30, 2021
• Last Update Posted: January 19, 2022
• Sponsor: Raziel Therapeutics Ltd.
• Information provided by (Responsible Party): Raziel Therapeutics Ltd.

Study Description

Brief Summary:

A total of 135 eligible male or female subjects will be randomized according to a predetermined randomization scheme (1:1:1 ratio) to receive a single multi-injection treatment of high dose RZL-012, low dose RZL-012, or placebo on Day 0. They will be monitored for safety and efficacy over 84 days.

Condition or disease	Intervention/treatment	Phase
Submental Fat	Drug: RZL-012; Drug: Placebo	Phase 2

Detailed Description:

Each subject will be randomized to either active treatment (high or low dose RZL-012) or placebo at a ratio of 1:1:1 per group and receive one of the following:

• low dose (concentration of injected solution 34 mg/mL RZL-012) of 5.1 mg/0.15 mL/injection point that results in a dose/volume of 163.2±20.4 mg/4.8±0.6 mL RZL-012,
• high dose (concentration of injected solution 50 mg/mL RZL-012) of 7.5 mg/0.15 mL/injection point that results in a maximum total dose/volume of 240±30 mg/4.8±0.6 mL RZL-012,
• placebo of 0.15 mL/injection point that results in a total maximum volume of 4.8±0.6 mL.

Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses of 183.6 mg and 270 mg for the low and high doses, respectively. Each injection point will be dosed with 5.1 mg RZL-012 for the low dose or 7.5 mg for the high dose in a volume of 0.15 mL/injection site. Placebo (vehicle) subjects will be injected with a 0.15 mL vehicle per each injection site. The maximal injection volume for all groups will be up to 5.4 mL.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 135 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double Blind, Randomized, Three Arm, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of RZL-012 in Subjects Seeking for Submental Fat Reduction
• Actual Study Start Date: June 15, 2021
• Estimated Primary Completion Date: April 20, 2022
• Estimated Study Completion Date: May 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: RZL-012 50mg/ml; Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses 270 mg for the high doses. Each injection point will be dosed with 7.5 mg for the high dose in a volume of 0.15 mL/injection site.	Drug: RZL-012; small synthetic molecule for submental fat reduction
Active Comparator: RZL-012 34mg/ml; Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses of 183.6 mg for the low dose. Each injection point will be dosed with 5.1 mg RZL-012 for the low dose in a volume of 0.15 mL/injection site.	Drug: RZL-012; small synthetic molecule for submental fat reduction
Placebo Comparator: Placebo; Placebo (vehicle) subjects will be injected with a 0.15 mL vehicle per each injection site. The maximal injection volume for all groups will be up to 5.4 mL.	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. Efficacy -Change in score according to Clinician chin assessment tool (C-CAT) [ Time Frame: 84 days ]
   To determine the efficacy of RZL-012 versus placebo on submental fat (SMF) reduction measured on Day 84 versus baseline using the Clinician Chin Assessment Tool (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

Secondary Outcome Measures :

1. Efficacy - Change in score according to Subject chin assessment tool (S-CAT) [ Time Frame: 84 days ]
   To determine the efficacy of RZL-012 versus placebo on submental fat (SMF) reduction measured 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
2. Efficacy - Reduction in submental fat volume [ Time Frame: 84 days ]
   Reduction from baseline in submental fat volume (mm^3), as measured with MRI in RZL-012 treated subjects vs. placebo treated subjects on Day 84 following injection.
3. Safety - Adverse events follow up [ Time Frame: 84 days ]
   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 treatment area. Treatment area evaluations including, but not limited to evaluation of edema, bruising, dysphasia, dysphonia, erythema, dyspigmentation, induration, numbness, pain, paresthesia, and pruritus. The number of subjects with treatment-related adverse events will be compared within each treatment group, as assessed by CTCAE v4.0.

Eligibility Criteria

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

Criteria

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 and <40.
3. Has SMF area that is contiguous and fits to 32±4 injections sites according to a grid with 1 cm distance between injection points.
4. Has moderate to severe grade 3 to 4 of SMF as rated by the C-SFS.
5. Has moderate to severe grade 3 to 4 of SMF as rated by the P-SFS.
6. Has stable weight, with no fluctuation of >5 kg in the past 12 months.

7. 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 7 days 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
   • 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 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.
8. If male (with or without vasectomy), agree to the use of highly effective contraceptive methods (as listed in Criterion #7 above) from study check-in until 7 days after the last day of study drug.
9. Is willing to avoid strenuous exercise for seven (7) days post treatment.
10. Is able to adhere to the visit schedule and protocol requirements and be available to complete the study.
11. 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:

Subjects must NOT meet any of the following Exclusion criteria to be eligible for enrollment:

1. Is unable to tolerate subcutaneous injections.
2. Has dysfunctional gallbladder activity (e.g., underwent cholecystectomy or cholecystitis).
3. Has any uncontrolled systemic disease that is not stabilized (i.e., cardiovascular disease, mental illness).
4. Has had treatment with botulinum toxin injections in the neck or chin area within nine (9) months prior to screening.
5. 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.
6. 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.
7. Has an extreme fat bulge under the chin and the submental fat was previously rated as 'very severe'.
8. Has fat extends down the neck beyond the Adam's Apple, towards the base of the neck where the fat extends laterally along the jawline making the jawline indistinguishable from the neck.
9. Has any scars, unshaven hair, tattoos, facial hair or jewelry on or near the proposed treatment area.
10. 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.
11. 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.
12. Has an active dermatitis or open wound in the proposed treatment area.
13. Has abnormal coagulation tests (PT, PTT)
14. Has D-dimer value >0.64mg/L in screening visit
15. Has an active bacterial, fungal, or viral infection in the proposed treatment area.
16. Has a pre-existing skin condition in the submental region that, at the Investigator's discretion, may confound evaluation or analysis.
17. 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.
18. Has pre-existing neurological or gastrointestinal condition leading to dysphagia, dysphonia, or facial nerve palsy.
19. Has Dercum's Disease
20. 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.
21. Has a planned fat reduction procedure of any variety to the submental region for the duration of the study.
22. Has medication or a history of coagulopathy.
23. Has a history or family history of venous thrombotic disease.
24. Has been treated chronically at least three (3) months prior to study entry with systemic steroids or immunosuppressive drugs.
25. Has been treated chronically at least one (1) week prior to study entry with non-steroidal anti-inflammatory drugs (NSAIDs).
26. Current participation or participation within three (3) months prior to the start of this study in a drug or other investigational research study.
27. Has claustrophobia or an MRI incompatible device or implant.

Contacts and Locations

Contacts

Contact: Racheli Gueta, PhD; 972-8-9126941; racheli@raziel-therapy.com

Locations

United States, Illinois

DenovaResearch; Recruiting

Chicago, Illinois, United States, 60611

Contact: Nimit Gandhi, MD nimit@denovaresearch.com

Sponsors and Collaborators

Raziel Therapeutics Ltd.

Investigators

• Study Director: Raceli Gueta, PhD; Raziel Therapeutics

More Information

• Responsible Party: Raziel Therapeutics Ltd.
• ClinicalTrials.gov Identifier: NCT04867434
• Other Study ID Numbers: RZL-012-SMF-P2b-US-001
• First Posted: April 30, 2021
• Last Update Posted: January 19, 2022
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No