Flank Mass
Conditions
Brief summary
A total of 12 subjects will be injected with RZL-012 and placebo. Each of the subject's flanks will be randomized for each of the treatment. A total of 24 flanks will be randomized in the double blind phase. They will be monitored for safety and efficacy for 12 weeks. After codes opening, a second treatment cycle on the previously untreated contralateral flank will be done. Subjects will be monitored for safety and efficacy for additional 12 weeks.
Detailed description
This clinical trial is comprised of a double-blind, placebo-controlled phase followed by an open-label phase. The double-blind, placebo-controlled phase of the trial will consist of a screening period, baseline visit and a 12-week post-treatment follow-up period. At the baseline visit, each flank (right and left) of each study participant will be randomized into either the active RZL-012 treatment group or the placebo group and each flank will receive multiple injections in a single session of RZL-012 or placebo. Blood samples will be collected for 6 of the 12 subjects for PK analyses. All subjects will be followed up for 12 weeks after the single treatment session. Upon completion of the double-blind phase of the study, and the opening of codes subjects will be offered RZL-012 open-label treatment in the flank previously treated with placebo. Consenting subjects will be followed for safety and efficacy for an additional 12 weeks. In both the double-blind and open-label phases of the study, subjects will be monitored for adverse events (AEs). Subjects will return to the site for visits at 1 week, 4 weeks, 8 weeks, and 12 weeks post treatment and will be monitored for safety and efficacy during these visits. Subjects who will be collected with PK will return to the clinic at Day 1 post injection for further PK samples. The dimensions of flanks will be measured using 3D images and volumetric calculations using Canfield 3D images.
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
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Each of the subject's flanks will be randomized for RZL-012 and placebo injections.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Is a male or female subject between the ages of 18 and 65 years, inclusive. * Has body mass index (BMI) BMI of ≥ 22 and \< 30. * Has clearly visible and palpable fat in the flanks * Has symmetrical appearance of right and left flanks * Agrees to maintain weight (i.e., within 5% of body weight) by not making any changes in diet. * Agree to avoid exposure of the treated area to the sun for at least 1 month after each treatment session. * 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 28 days after the last day of study drug and a negative urine pregnancy test at screening and 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, having documented serum follicle-stimulating hormone (FSH) level \> 40 mIU/mL, or having another documented medical condition (e.g., was born without a uterus)) * If male (with or without vasectomy), agree to the use of highly effective contraceptive methods, e.g. condom, from study baseline until 7 days after the last day of study drug. * Is willing to avoid strenuous exercise for seven (7) days post treatment. * Is motivated to adhere to the visit schedule and protocol requirements. * 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
* Is unable to tolerate subcutaneous injections. * Has dysfunctional gallbladder activity (e.g., underwent cholecystectomy or cholecystitis). * Has an uncontrolled systemic disease that is not stabilized (i.e., cardiovascular disease, mental illness). * 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. * Has medication or a history of coagulopathy. * Has a history or family history of venous thrombotic disease. * Had a non-invasive fat reduction and/or body contouring procedure in the flanks within the past 12 months. * Has any scars, unshaven hair, tattoos, on or near the proposed treatment area. * 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. * Has an active dermatitis or open wound in the proposed treatment area. * Abnormal coagulation profile including: activated partial thromboplastin time (aPTT) \> ULN, international normalized ratio (INR) \> ULN reference range (\> 1.3), prothrombin time (PT) \> ULN. * Has an active bacterial, fungal, or viral infection in the proposed treatment area. * Has known allergic reactions to any injectables. * Has been treated chronically in the past 3 months prior to study entry with systemic steroids or immunosuppressive drugs. * Has been treated chronically at least one (1) week prior to study entry with non-steroidal anti-inflammatory drugs (NSAIDs). * 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 |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events [AEs] | 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase | Safety |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase | To compare the proportion of flanks having an improvement as indicated by reduction in score from 6 to 0 according to the Physician Global Assessment Scale (GAIS) in RZL-01-treated flanks vs placebo-treated flanks |
| Efficacy - Change in Satisfaction Score | 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase | To compare the proportion of subjects who are satisfied with treatment results as indicated by a binary yes/no satisfaction questionnaire in RZL-012-treated flanks vs placebo-treated flanks |
| Efficacy - Relative Change in Measured Fat Volume | 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase. Baseline for the open-label phase considered to be 12 weeks after double blind treatment | Measure the relative mean reduction in volume (%) at post treatment vs. baseline for each of the treated flanks, as measured by 3D images using the Canfield 3D system in RZL-012-treated flanks vs placebo-treated flanks at 12 weeks vs. baseline |
| Efficacy -Number of Participant With Correct Identification by Reviewers | 12 weeks 12 weeks for the Double-Blind Phase | Blinded reviewers will identify, per patient, the flank treated with test compound (active) vs the flank treated with Placebo. Success will be defined as at least 70% correct identification vs the expected 50% correct identification based on random guessing |
| Pharmacokinetics Measure - Drug Concentration in the Blood (ng/mL) | 30 hours | Measurement of maximum drug concentration (Cmax) (ng/mL) in the blood |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RZL-012 50mg/ml or Placebo Subjects flanks treated with RZL-012 (in the double blind phase) will undergo a single treatment session with 50-55 injections. The maximal number of injections will be 55 with maximal doses 412.5 mg. Each injection point will be dosed with 7.5 mg for in a volume of 0.15 mL/injection site.
RZL-012: small synthetic molecule for submental fat reduction
Subjects flanks treated with placebo (in the double blind phase) will undergo a single treatment session with 50-55 injections. The maximal number of injections will be 55 with maximal volume of 8.25mL. Each injection point will be dosed with 0.15 mL/injection site.
Placebo: Placebo | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Double Blind Part | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | RZL-012 50mg/ml or Placebo |
|---|---|
| Age, Continuous Double blind phase | 43 years STANDARD_DEVIATION 12.2 |
| Age, Continuous Open Label phase | 44.1 years STANDARD_DEVIATION 10.6 |
| Race (NIH/OMB) Double Blind phase American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Double Blind phase Asian | 0 Participants |
| Race (NIH/OMB) Double Blind phase Black or African American | 2 Participants |
| Race (NIH/OMB) Double Blind phase More than one race | 0 Participants |
| Race (NIH/OMB) Double Blind phase Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Double Blind phase Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Double Blind phase White | 10 Participants |
| Race (NIH/OMB) Open label phase American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Open label phase Asian | 0 Participants |
| Race (NIH/OMB) Open label phase Black or African American | 1 Participants |
| Race (NIH/OMB) Open label phase More than one race | 0 Participants |
| Race (NIH/OMB) Open label phase Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Open label phase Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Open label phase White | 8 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Double blind phase Female | 10 Participants |
| Sex: Female, Male Double blind phase Male | 2 Participants |
| Sex: Female, Male Open Label phase Female | 7 Participants |
| Sex: Female, Male Open Label phase Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 12 / 12 | 12 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Number of Participants With Treatment-related Adverse Events [AEs]
Safety
Time frame: 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase
Population: The data for double blind and open label phase are presented. A total of 9 subjects continued to open label phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RZL-012 50mg/ml | Number of Participants With Treatment-related Adverse Events [AEs] | Related to Injection Procedure | 12 participants |
| RZL-012 50mg/ml | Number of Participants With Treatment-related Adverse Events [AEs] | AE Related Study Treatment | 12 participants |
| RZL-012 50mg/ml | Number of Participants With Treatment-related Adverse Events [AEs] | Severe Adverse Events | 0 participants |
| Placebo | Number of Participants With Treatment-related Adverse Events [AEs] | Related to Injection Procedure | 12 participants |
| Placebo | Number of Participants With Treatment-related Adverse Events [AEs] | AE Related Study Treatment | 12 participants |
| Placebo | Number of Participants With Treatment-related Adverse Events [AEs] | Severe Adverse Events | 0 participants |
| RZL-012 Open Label | Number of Participants With Treatment-related Adverse Events [AEs] | AE Related Study Treatment | 9 participants |
| RZL-012 Open Label | Number of Participants With Treatment-related Adverse Events [AEs] | Severe Adverse Events | 0 participants |
| RZL-012 Open Label | Number of Participants With Treatment-related Adverse Events [AEs] | Related to Injection Procedure | 9 participants |
Secondary
Efficacy - Change in Satisfaction Score
To compare the proportion of subjects who are satisfied with treatment results as indicated by a binary yes/no satisfaction questionnaire in RZL-012-treated flanks vs placebo-treated flanks
Time frame: 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase
Population: A total of 9subjects continued to the open label phase
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| RZL-012 50mg/ml | Efficacy - Change in Satisfaction Score | RZL-012 - Double blind phase | Satisfied | 9 Participants |
| RZL-012 50mg/ml | Efficacy - Change in Satisfaction Score | RZL-012 - Double blind phase | Not Satisfied | 2 Participants |
| RZL-012 50mg/ml | Efficacy - Change in Satisfaction Score | Placebo Double blind phase | Satisfied | 1 Participants |
| RZL-012 50mg/ml | Efficacy - Change in Satisfaction Score | Placebo Double blind phase | Not Satisfied | 10 Participants |
| RZL-012 50mg/ml | Efficacy - Change in Satisfaction Score | RZL-012 Open Label phase | Satisfied | 6 Participants |
| RZL-012 50mg/ml | Efficacy - Change in Satisfaction Score | RZL-012 Open Label phase | Not Satisfied | 3 Participants |
Secondary
Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale
To compare the proportion of flanks having an improvement as indicated by reduction in score from 6 to 0 according to the Physician Global Assessment Scale (GAIS) in RZL-01-treated flanks vs placebo-treated flanks
Time frame: 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase
Population: A total of 9 subjects continued to the open label phase
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RZL-012 50mg/ml | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | Marked Improvement | 7 flanks |
| RZL-012 50mg/ml | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | Moderate Improvement | 2 flanks |
| RZL-012 50mg/ml | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | Slight Improvement | 1 flanks |
| RZL-012 50mg/ml | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | No Change | 1 flanks |
| Placebo | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | No Change | 11 flanks |
| Placebo | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | Marked Improvement | 0 flanks |
| Placebo | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | Slight Improvement | 0 flanks |
| Placebo | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | Moderate Improvement | 0 flanks |
| RZL-012 Open Label | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | No Change | 2 flanks |
| RZL-012 Open Label | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | Moderate Improvement | 0 flanks |
| RZL-012 Open Label | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | Slight Improvement | 7 flanks |
| RZL-012 Open Label | Efficacy - Number of Flanks That Have Change in Score According Physician Global Assessment Scale | Marked Improvement | 0 flanks |
Secondary
Efficacy -Number of Participant With Correct Identification by Reviewers
Blinded reviewers will identify, per patient, the flank treated with test compound (active) vs the flank treated with Placebo. Success will be defined as at least 70% correct identification vs the expected 50% correct identification based on random guessing
Time frame: 12 weeks 12 weeks for the Double-Blind Phase
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RZL-012 50mg/ml | Efficacy -Number of Participant With Correct Identification by Reviewers | Reviewer 1 - Correct identification of active treated flanks | 5 Participants |
| RZL-012 50mg/ml | Efficacy -Number of Participant With Correct Identification by Reviewers | Reviewer 2 - Correct identification of active treated flanks | 6 Participants |
Secondary
Efficacy - Relative Change in Measured Fat Volume
Measure the relative mean reduction in volume (%) at post treatment vs. baseline for each of the treated flanks, as measured by 3D images using the Canfield 3D system in RZL-012-treated flanks vs placebo-treated flanks at 12 weeks vs. baseline
Time frame: 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase. Baseline for the open-label phase considered to be 12 weeks after double blind treatment
Population: A total of 9 subjects continued to the open label phase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RZL-012 50mg/ml | Efficacy - Relative Change in Measured Fat Volume | -37 percentage of change from baseline. | Standard Deviation 55.2 |
| Placebo | Efficacy - Relative Change in Measured Fat Volume | 33 percentage of change from baseline. | Standard Deviation 41.4 |
| RZL-012 Open Label | Efficacy - Relative Change in Measured Fat Volume | -48.9 percentage of change from baseline. | Standard Deviation 65.9 |
Secondary
Pharmacokinetics Measure - Drug Concentration in the Blood (ng/mL)
Measurement of maximum drug concentration (Cmax) (ng/mL) in the blood
Time frame: 30 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RZL-012 50mg/ml | Pharmacokinetics Measure - Drug Concentration in the Blood (ng/mL) | 961.8 ng/ml | Standard Error 273.4 |