Submental Fat
Conditions
Brief summary
Twenty-Eight (28) subjects (12 for cohort 1 and 16 for cohort 2 ) will be included in the study. Subjects in each cohort will be injected with a different dose of RZL-012. The total of 28 subjects will be enrolled in 2 clinical sites.
Detailed description
This is a single blinded, randomized, placebo-controlled, 2-cohort clinical study in healthy volunteers. Cohort 1 will be comprised of 8 active (RZL-012) and 4 placebo subjects. Cohort 2 will be comprised of 16 subjects wuth at least 4 placebo subjects. All subjects will receive a single dose of RZL-012 or vehicle into the submental area, after which they will be monitored for safety and efficacy during 84 days of follow-up. Subjects will be blinded to study treatment while physicians will not be blinded. The study will be composed of 2 treatment cohorts, 12 in cohort 1 and 16 in cohort 2. The study will be conducted in 2 clinical sites. Per each study cohort, subjects will be randomized to receive active or placebo treatment according to a randomization program that will be prepared prior to study initiation. Each clinical site will have at least one active and one placebo treatment subject per each study cohorts. In case of slow enrollment in one of the sites, other sites may complete the enrollment of subjects in each cohort. Cohort 1 (N=12) - Each subject will be dosed with up to 120 mg RZL-012 (depending on submental fat area) or vehicle. Cohort 2 (N=16) - Each subject will be dosed with up to 240 mg RZL-012 (depending on submental fat area) or vehicle. Treatment of cohort 2 will start following cohort 1 day 28 data. An independent Data Safety Monitoring Board (DSMB) will review safety and tolerability data for cohort 1 subjects, 28 days after injection, and decide whether it is safe to increase the dose for the next study cohort. The decision to proceed to the cohort 2 will be made within 30 days (28 days + 2 days) after injection of the last dosed subject in cohort 1. The DSMB will be comprised of two independent MDs with expertise in the aesthetic area and in conduction of clinical trials. In case of serious safety concerns (e.g. prolonged severe swelling or severe pain following injection) among cohort 1 subjects receiving the 120mg dose, sponsor and DSMB may decide to reduce or stay with the 120mg/subject dose level for cohort 2 subjects.
Interventions
DRUGRZL-012
Subcutaneous injection to the submental fat area
DRUGPlacebo
Placebo
Sponsors
Raziel Therapeutics Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Men and women 18-65 years old. 2. Subjects with Body Mass Index \<35 3. Subjects must have submental skin fold thickness greater than 1.5 cm as measured with calipers. 4. Males must be willing to be clean shaved for all study visits. 5. Patient weight must be stable (no fluctuation of \>15 pounds in the past year) 6. Males or females in the age of fertility agree to use a double-barrier contraceptive device (e.g., condom and spermicide) for 4 weeks after treatment with RZL 012. 7. Subjects must be able to adhere to the visit schedule and protocol requirements and be available to complete the study. 8. Subjects must sign an IRB approved informed consent indicating they are aware of the investigational nature of the study.
Exclusion criteria
Subjects meeting any of the following criteria will be excluded from study participation: 1. Unable to tolerate subcutaneous injection. 2. Pregnant or lactating women. 3. Subjects with dysfunctional gallbladder activity, e.g. underwent cholecystectomy or cholecystitis. 4. Any uncontrolled systemic disease -a potential patient in whom therapy for a systemic disease is not yet stabilized will not be considered for entry into the study 5. Treatment with botulinum toxin injections in the neck or chin area within 6 months before screening. 6. Excessive submental skin laxity. 7. Any Scars, unshaven hair, tattoos or jewelry on or near the proposed treatment area 8. Significant history or current evidence of a medical, psychological or other disorder that, in the investigator's opinion, would preclude enrollment into the study 9. An active dermatitis or open wound in the proposed treatment area 10. An active bacterial, fungal, or viral infection in the proposed treatment area 11. Pre-existing skin condition in the submental region that may confound evaluation or analysis, at investigator discretion 12. Previously treated with focused ultrasound, radiofrequency, cryolipolysis, liposuction, sodium deoxycholate to the submental region within the previous 6 months 13. Pre-existing neurological or gastrointestinal condition leading to dysphagia, dysphonia or facial nerve palsy 14. Pre-existing medical condition other than increased submental fat that may result in increased submental fullness such as but not limited to thyroid enlargement, goiter, cervical lymphadenopathy etc., at investigator discretion 15. Must not have a planned fat reduction procedure of any variety to the submental region for the duration of the study 16. Must not have planned significant alterations in diet or physical activity that may result in significant fluctuations in weight. 17. Subjects with medication or history of coagulopathy. 18. Allergic subjects to Bendaryl. 19. Subjects treated chronically at least 3 months prior to study entry with systemic steroids or immunosuppressive drugs. 20. Subjects treated chronically at least one week prior to study entry with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). 21. Current participation or participation within 3 months prior to the start of this study in a drug or other investigational research study. 22. Claustrophobia or MRI incompatible device or implant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Adverse Events Follow up | 0-84 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 subjects. Specifically, Pain, Induration, Bruising, Erythema and Edema will be closely followed up following treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physician's Global Assessment | 0-84 days | Evaluation of treatment efficacy by using Physician's global assessment questionnaire for active vs. placebo subjects, on study Day 84 |
| Efficacy: MRI Volume Reduction | 0-84 days | 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. |
| Efficacy: Improvement in Face Satisfaction Questionnaire - A Score From 0 (Worst) to 100 (Best) Marks the Subject's Satisfaction | 0-84 days | Improvement from baseline in the Faceq satisfaction questionnaire rating score in RZL-012 treated subjects vs. placebo treated subjects on day 84. |
Countries
United States
Participant flow
Pre-assignment details
The safety and efficacy of exposed subjects to RZL-012 were compared to exposed subjects with placebo
Participants by arm
| Arm | Count |
|---|---|
| RZL-012 Cohort 1 A single-treatment injection, multiple subcutaneous injections of RZL-012 administered into 48 sites in the submental fat (0.05mL per site):
Up to 120mg administered at 48 sites in a volume of 0.05 ml at each injection site (total injected volume 2.4mL)
RZL-012: Subcutaneous injection to the submental fat area | 8 |
| Vehicle Cohort 1 Subject receive a single-treatment injection. Multiple injections of the Placebo are administered at 48 sites (0.05mL per site) into the submental fat.
Up to a total .of 2.4 mL will be injected for placebo subjects enrolled during cohort 2.
Placebo: Placebo | 4 |
| RZL-012 Cohort 2 A single-treatment injection, multiple subcutaneous injections of RZL-012 administered into 48 sites in the submental fat (0.1mL per site):
Up to 240 mg administered at 48 sites in a volume of 1 ml at each injection site (total volume injected 4.8mL)
RZL-012: Subcutaneous injection to the submental fat area | 10 |
| Vehicle Cohort 2 Subject receive a single-treatment injection. Multiple injections of the Placebo are administered at 48 sites (0.1mL per site) into the submental fat.
Up to a total of 4.8 mL will be injected for placebo subjects enrolled during cohort 2.
Placebo: Placebo | 6 |
| Total | 28 |
Baseline characteristics
| Characteristic | RZL-012 Cohort 1 | Total | Vehicle Cohort 2 | RZL-012 Cohort 2 | Vehicle Cohort 1 |
|---|---|---|---|---|---|
| Age, Continuous | 51.6 years STANDARD_DEVIATION 6.8 | 49.65 years STANDARD_DEVIATION 9.6 | 48.8 years STANDARD_DEVIATION 10.2 | 43.3 years STANDARD_DEVIATION 9.5 | 57.5 years STANDARD_DEVIATION 8.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 26 Participants | 5 Participants | 9 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 27 Participants | 6 Participants | 9 Participants | 4 Participants |
| Region of Enrollment United States | 8 Participants | 28 Participants | 6 Participants | 10 Participants | 4 Participants |
| Sex: Female, Male Female | 6 Participants | 24 Participants | 6 Participants | 9 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 4 | 0 / 10 | 0 / 6 |
| other Total, other adverse events | 8 / 8 | 4 / 4 | 10 / 10 | 6 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 4 | 0 / 10 | 0 / 6 |
Outcome results
Primary
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 subjects. Specifically, Pain, Induration, Bruising, Erythema and Edema will be closely followed up following treatment.
Time frame: 0-84 days
Population: Safety Analysis consist of all enrolled subjects who received the study treatment, (exposed population), vs. placebo treated subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RZL-012 Cohort 1 | Safety: Adverse Events Follow up | 8 Participants |
| Vehicle | Safety: Adverse Events Follow up | 4 Participants |
| RZL-012 Cohort 2 | Safety: Adverse Events Follow up | 10 Participants |
| Vehicle Cohort 2 | Safety: Adverse Events Follow up | 6 Participants |
Secondary
Efficacy: Improvement in Face Satisfaction Questionnaire - A Score From 0 (Worst) to 100 (Best) Marks the Subject's Satisfaction
Improvement from baseline in the Faceq satisfaction questionnaire rating score in RZL-012 treated subjects vs. placebo treated subjects on day 84.
Time frame: 0-84 days
Population: The questionnaire efficacy included all exposed population to RZL-012 vs. all treated subjects by placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RZL-012 Cohort 1 | Efficacy: Improvement in Face Satisfaction Questionnaire - A Score From 0 (Worst) to 100 (Best) Marks the Subject's Satisfaction | 34.8 change in scores on a scale | Standard Deviation 10 |
| Vehicle | Efficacy: Improvement in Face Satisfaction Questionnaire - A Score From 0 (Worst) to 100 (Best) Marks the Subject's Satisfaction | -3.8 change in scores on a scale | Standard Deviation 29.2 |
| RZL-012 Cohort 2 | Efficacy: Improvement in Face Satisfaction Questionnaire - A Score From 0 (Worst) to 100 (Best) Marks the Subject's Satisfaction | 38.5 change in scores on a scale | Standard Deviation 25 |
| Vehicle Cohort 2 | Efficacy: Improvement in Face Satisfaction Questionnaire - A Score From 0 (Worst) to 100 (Best) Marks the Subject's Satisfaction | -1.2 change in scores on a scale | Standard Deviation 16.3 |
Secondary
Efficacy: MRI Volume Reduction
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.
Time frame: 0-84 days
Population: The efficacy in the MRI was divided to per treated doses cohorts
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RZL-012 Cohort 1 | Efficacy: MRI Volume Reduction | Cohort 2 High Dose (BioClinica Analysis) | -12.5 percentage of volume reduction high dose | Standard Deviation 8 |
| RZL-012 Cohort 1 | Efficacy: MRI Volume Reduction | Cohort 1 Low Dose (Bioclinica Analysis) | -6.4 percentage of volume reduction high dose | Standard Deviation 11 |
| Vehicle | Efficacy: MRI Volume Reduction | Cohort 2 High Dose (BioClinica Analysis) | 0.7 percentage of volume reduction high dose | Standard Deviation 8.5 |
| Vehicle | Efficacy: MRI Volume Reduction | Cohort 1 Low Dose (Bioclinica Analysis) | -5.7 percentage of volume reduction high dose | Standard Deviation 3 |
Secondary
Physician's Global Assessment
Evaluation of treatment efficacy by using Physician's global assessment questionnaire for active vs. placebo subjects, on study Day 84
Time frame: 0-84 days
Population: Subjects were analysed according to the treatment received.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RZL-012 Cohort 1 | Physician's Global Assessment | Subjects experienced improvement (Score =0 (completely clear) , 1, 2, 3, Score=4(slight improvement) | 7 Participants |
| RZL-012 Cohort 1 | Physician's Global Assessment | Subjects that experienced no improvement = Score 5 (no Change) | 1 Participants |
| Vehicle | Physician's Global Assessment | Subjects that experienced no improvement = Score 5 (no Change) | 4 Participants |
| Vehicle | Physician's Global Assessment | Subjects experienced improvement (Score =0 (completely clear) , 1, 2, 3, Score=4(slight improvement) | 0 Participants |
| RZL-012 Cohort 2 | Physician's Global Assessment | Subjects experienced improvement (Score =0 (completely clear) , 1, 2, 3, Score=4(slight improvement) | 10 Participants |
| RZL-012 Cohort 2 | Physician's Global Assessment | Subjects that experienced no improvement = Score 5 (no Change) | 0 Participants |
| Vehicle Cohort 2 | Physician's Global Assessment | Subjects experienced improvement (Score =0 (completely clear) , 1, 2, 3, Score=4(slight improvement) | 0 Participants |
| Vehicle Cohort 2 | Physician's Global Assessment | Subjects that experienced no improvement = Score 5 (no Change) | 6 Participants |