Submental Fat
Conditions
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.
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.
Interventions
DRUGRZL-012
small synthetic molecule for submental fat reduction
DRUGPlacebo
Placebo
Sponsors
Raziel Therapeutics Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy -Proportion of Subjects With at Least a 1-grade Improvement in the C-CAT Scale at Day 84 | 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
| Measure | Time frame | Description |
|---|---|---|
| Efficacy - the Proportion of Subjects With at Least 1-grade Improvement in Subject Chin Assessment Tool (S-CAT) | 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 |
| Efficacy - Relative Change in Submental Fat Volume on Day 84 vs. Baseline | 84 days | Percent 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 vs. baseline. |
| Safety - Adverse Events Follow up | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
RZL-012: small synthetic molecule for submental fat reduction | 50 |
| 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.
RZL-012: small synthetic molecule for submental fat reduction | 53 |
| 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.
Placebo: Placebo | 48 |
| Total | 151 |
Baseline characteristics
| Characteristic | RZL-012 50mg/ml | RZL-012 34mg/ml | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 44.6 years STANDARD_DEVIATION 9.7 | 42.8 years STANDARD_DEVIATION 10.7 | 41.6 years STANDARD_DEVIATION 10.8 | 43 years STANDARD_DEVIATION 10.6 |
| Race/Ethnicity, Customized Race American Indian Or Alaska Native | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Asian | 4 Participants | 5 Participants | 5 Participants | 14 Participants |
| Race/Ethnicity, Customized Race Black Or African American | 5 Participants | 4 Participants | 5 Participants | 14 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian Or Other Pacific | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Not reported or Unknown | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Race White | 37 Participants | 39 Participants | 36 Participants | 112 Participants |
| Region of Enrollment United States | 50 Participants | 53 Participants | 48 Participants | 151 Participants |
| Sex: Female, Male Female | 42 Participants | 45 Participants | 34 Participants | 121 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 14 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 53 | 0 / 48 |
| other Total, other adverse events | 49 / 50 | 51 / 53 | 48 / 48 |
| serious Total, serious adverse events | 0 / 50 | 0 / 53 | 0 / 48 |
Outcome results
Primary
Efficacy -Proportion of Subjects With at Least a 1-grade Improvement in the C-CAT Scale at Day 84
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
Time frame: 84 days
Population: The proportion of subjects who have at least a 1-grade improvement in the C-CAT on Day 84 versus baseline will be calculated for the placebo group and the RZL-012 high-dose group along with 95% Confidence interval for proportion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RZL-012 50mg/ml | Efficacy -Proportion of Subjects With at Least a 1-grade Improvement in the C-CAT Scale at Day 84 | 43 participants |
| RZL-012 34mg/ml | Efficacy -Proportion of Subjects With at Least a 1-grade Improvement in the C-CAT Scale at Day 84 | 39 participants |
| Placebo | Efficacy -Proportion of Subjects With at Least a 1-grade Improvement in the C-CAT Scale at Day 84 | 27 participants |
Secondary
Efficacy - Relative Change in Submental Fat Volume on Day 84 vs. Baseline
Percent 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 vs. baseline.
Time frame: 84 days
Population: The Paired T-test for two means (paired observations) will be applied for testing the statistical significance of the change and percentage of change from baseline at Day 84 in SMF thickness measured with caliper and in SMF volume by MRI within each study group
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RZL-012 50mg/ml | Efficacy - Relative Change in Submental Fat Volume on Day 84 vs. Baseline | -14.92 percentage of volume reduction | Standard Deviation 9.98 |
| RZL-012 34mg/ml | Efficacy - Relative Change in Submental Fat Volume on Day 84 vs. Baseline | -8.34 percentage of volume reduction | Standard Deviation 11.72 |
| Placebo | Efficacy - Relative Change in Submental Fat Volume on Day 84 vs. Baseline | 1.45 percentage of volume reduction | Standard Deviation 8.68 |
Secondary
Efficacy - the Proportion of Subjects With at Least 1-grade Improvement in Subject Chin Assessment Tool (S-CAT)
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
Time frame: 84 days
Population: \- The Chi-Square test will be applied to test the statistical difference between the placebo group and each of the RZL-012 dose groups in the responder rate at Day 84 where responder rate is defined as the percentage of subject achieving at least a 1-grade improvement from baseline in S-CAT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RZL-012 50mg/ml | Efficacy - the Proportion of Subjects With at Least 1-grade Improvement in Subject Chin Assessment Tool (S-CAT) | 43 participants |
| RZL-012 34mg/ml | Efficacy - the Proportion of Subjects With at Least 1-grade Improvement in Subject Chin Assessment Tool (S-CAT) | 42 participants |
| Placebo | Efficacy - the Proportion of Subjects With at Least 1-grade Improvement in Subject Chin Assessment Tool (S-CAT) | 30 participants |
Secondary
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 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.
Time frame: 84 days
Population: The incidence of AEs will be presented by treatment. Descriptive statistics will be calculated for quantitative data and frequency counts and percentages will be provided for categorical data. All reported AEs are treatment related
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | pain | 4 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site induration | 7 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site hemorrhage | 6 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Dyspnea | 2 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site hypersensitivity | 2 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site hypoesthesia | 15 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Burning sensation | 0 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Localized edema | 10 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site mass | 5 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site warmth | 0 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site swelling | 17 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site pain | 34 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Induration | 1 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site pruritus | 5 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site paresthesia | 0 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Hypoesthesia | 3 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site nodule | 2 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site dermatitis | 0 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Facial paralysis | 3 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Tenderness | 0 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Headache | 3 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Dysphagia | 15 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Swelling | 1 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site discomfort | 2 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site edema | 21 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Dysphonia | 2 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Dizziness | 2 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site bruising | 18 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Facial nerve disorder | 1 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site movement impairement | 3 participants |
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | Injection site erythema | 7 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site discomfort | 3 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Facial paralysis | 1 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Hypoesthesia | 0 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Dysphonia | 2 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Dyspnea | 2 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Induration | 1 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site dermatitis | 0 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Dysphagia | 21 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site edema | 27 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site bruising | 17 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site erythema | 4 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site hemorrhage | 10 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site hypoesthesia | 15 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site mass | 4 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site pain | 31 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site paresthesia | 2 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site pruritus | 5 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site swelling | 18 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Localized edema | 6 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site hypersensitivity | 1 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site induration | 7 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site movement impairement | 1 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Dizziness | 2 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Headache | 4 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Tenderness | 0 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site nodule | 1 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Injection site warmth | 1 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | pain | 4 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Swelling | 0 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Burning sensation | 0 participants |
| RZL-012 34mg/ml | Safety - Adverse Events Follow up | Facial nerve disorder | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site induration | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site bruising | 20 participants |
| Placebo | Safety - Adverse Events Follow up | pain | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site movement impairement | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site edema | 27 participants |
| Placebo | Safety - Adverse Events Follow up | Hypoesthesia | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site dermatitis | 1 participants |
| Placebo | Safety - Adverse Events Follow up | Dysphagia | 2 participants |
| Placebo | Safety - Adverse Events Follow up | Headache | 3 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site discomfort | 1 participants |
| Placebo | Safety - Adverse Events Follow up | Dizziness | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Swelling | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Tenderness | 1 participants |
| Placebo | Safety - Adverse Events Follow up | Induration | 1 participants |
| Placebo | Safety - Adverse Events Follow up | Facial paralysis | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site nodule | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site paresthesia | 1 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site pain | 23 participants |
| Placebo | Safety - Adverse Events Follow up | Dyspnea | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site pruritus | 6 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site mass | 1 participants |
| Placebo | Safety - Adverse Events Follow up | Facial nerve disorder | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site swelling | 16 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site hypoesthesia | 12 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site warmth | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Localized edema | 3 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site hemorrhage | 7 participants |
| Placebo | Safety - Adverse Events Follow up | Dysphonia | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site hypersensitivity | 0 participants |
| Placebo | Safety - Adverse Events Follow up | Injection site erythema | 3 participants |
| Placebo | Safety - Adverse Events Follow up | Burning sensation | 1 participants |