Submental Fat
Conditions
Brief summary
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:
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.
Interventions
DRUGRZL-012
50mg/ml drug formulation
DRUGRZL-012+Lidacaine injection prior treatment
5ml lidocaine will be injected 10 minutes before RZL-012 treatment
DRUGRZL-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
DRUGRZL-012+Celecoxib+Zyrtec
200 mg Celecoxib BID and 10 mg Zyrtec BID on Days 1, 2, 3, 4, 5 and 6
DRUGRZL-012+facial and neck wrap
Universal Facial Band
Sponsors
Raziel Therapeutics Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Adverse Events Follow up | 84 days | Number of subjects with severe swelling in each subgroup |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy -Reduction in Score According to Clinician Chin Assessment Tool (C-CAT) | 84 days | 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 |
| Efficacy - Number of Participants With 1 Grade Improvement According to the Subject Chin Assessment Tool (S-CAT) | 84 days | 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 |
| Efficacy - Percentage of Change From Baseline in Submental Fat Volume | 84 days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RZL-012 50mg/ml RZL-012: 50mg/ml drug formulation | 8 |
| RZL-012+Lidacaine RZL-012+Lidacaine injection prior treatment: 5ml lidocaine will be injected 10 minutes before RZL-012 treatment | 10 |
| RZL-012+Medrol 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 | 9 |
| RZL-012+Celecoxib+Zyrtec RZL-012+Celecoxib+Zyrtec: 200 mg Celecoxib BID and 10 mg Zyrtec BID on Days 1, 2, 3, 4, 5 and 6 | 11 |
| RZL-012+Facial and Neck Wrap RZL-012+facial and neck wrap: Universal Facial Band | 10 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | RZL-012 50mg/ml | Total | RZL-012+Facial and Neck Wrap | RZL-012+Celecoxib+Zyrtec | RZL-012+Medrol | RZL-012+Lidacaine |
|---|---|---|---|---|---|---|
| Age, Continuous | 48.9 Years STANDARD_DEVIATION 7.2 | 45.9 Years STANDARD_DEVIATION 9.1 | 36.8 Years STANDARD_DEVIATION 5.7 | 44 Years STANDARD_DEVIATION 9.5 | 49.8 Years STANDARD_DEVIATION 6.5 | 51.1 Years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 47 Participants | 10 Participants | 11 Participants | 9 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 11 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 34 Participants | 6 Participants | 8 Participants | 8 Participants | 7 Participants |
| Region of Enrollment United States | 8 participants | 48 participants | 10 participants | 11 participants | 9 participants | 10 participants |
| Sex: Female, Male Female | 8 Participants | 42 Participants | 8 Participants | 9 Participants | 8 Participants | 9 Participants |
| Sex: Female, Male Male | 0 Participants | 6 Participants | 2 Participants | 2 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 | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 10 | 0 / 9 | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 8 / 8 | 10 / 10 | 9 / 9 | 11 / 11 | 10 / 10 |
| serious Total, serious adverse events | 0 / 8 | 0 / 10 | 0 / 9 | 1 / 11 | 0 / 10 |
Outcome results
Primary
Safety - Adverse Events Follow up
Number of subjects with severe swelling in each subgroup
Time frame: 84 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RZL-012 50mg/ml | Safety - Adverse Events Follow up | 1 Participants |
| RZL-012+Lidacaine Injection Prior Treatment | Safety - Adverse Events Follow up | 2 Participants |
| RZL-012+Methylprednisolone (Medrol) | Safety - Adverse Events Follow up | 3 Participants |
| RZL-012+Celecoxib+Zyrtec | Safety - Adverse Events Follow up | 0 Participants |
| RZL-012+Facial and Neck Wrap | Safety - Adverse Events Follow up | 0 Participants |
Secondary
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
Time frame: 84 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RZL-012 50mg/ml | Efficacy - Number of Participants With 1 Grade Improvement According to the Subject Chin Assessment Tool (S-CAT) | 4 Participants |
| RZL-012+Lidacaine Injection Prior Treatment | Efficacy - Number of Participants With 1 Grade Improvement According to the Subject Chin Assessment Tool (S-CAT) | 3 Participants |
| RZL-012+Methylprednisolone (Medrol) | Efficacy - Number of Participants With 1 Grade Improvement According to the Subject Chin Assessment Tool (S-CAT) | 6 Participants |
| RZL-012+Celecoxib+Zyrtec | Efficacy - Number of Participants With 1 Grade Improvement According to the Subject Chin Assessment Tool (S-CAT) | 6 Participants |
| RZL-012+Facial and Neck Wrap | Efficacy - Number of Participants With 1 Grade Improvement According to the Subject Chin Assessment Tool (S-CAT) | 5 Participants |
Secondary
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.
Time frame: 84 days
Population: There were only 33/46 subjects that had an MRI scan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RZL-012 50mg/ml | Efficacy - Percentage of Change From Baseline in Submental Fat Volume | -7.1 percentage of change from baseline | Standard Deviation 6 |
| RZL-012+Lidacaine Injection Prior Treatment | Efficacy - Percentage of Change From Baseline in Submental Fat Volume | -15.4 percentage of change from baseline | Standard Deviation 10.2 |
| RZL-012+Methylprednisolone (Medrol) | Efficacy - Percentage of Change From Baseline in Submental Fat Volume | -17.0 percentage of change from baseline | Standard Deviation 12.9 |
| RZL-012+Celecoxib+Zyrtec | Efficacy - Percentage of Change From Baseline in Submental Fat Volume | -10.8 percentage of change from baseline | Standard Deviation 9.8 |
| RZL-012+Facial and Neck Wrap | Efficacy - Percentage of Change From Baseline in Submental Fat Volume | -14.8 percentage of change from baseline | Standard Deviation 7.6 |
Secondary
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
Time frame: 84 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RZL-012 50mg/ml | Efficacy -Reduction in Score According to Clinician Chin Assessment Tool (C-CAT) | 6 Participants |
| RZL-012+Lidacaine Injection Prior Treatment | Efficacy -Reduction in Score According to Clinician Chin Assessment Tool (C-CAT) | 10 Participants |
| RZL-012+Methylprednisolone (Medrol) | Efficacy -Reduction in Score According to Clinician Chin Assessment Tool (C-CAT) | 9 Participants |
| RZL-012+Celecoxib+Zyrtec | Efficacy -Reduction in Score According to Clinician Chin Assessment Tool (C-CAT) | 8 Participants |
| RZL-012+Facial and Neck Wrap | Efficacy -Reduction in Score According to Clinician Chin Assessment Tool (C-CAT) | 9 Participants |