Glabellar Frown Lines (GL)
Conditions
Brief summary
To evaluate the safety and efficacy of EB-001 compared to placebo in subjects with glabellar frown lines (GL).
Detailed description
This study of EB-001 to measure safety and efficacy in GL. Single doses of EB- 001 administered through IM injection into procerus at midline and the medial and lateral corrugators will be assessed in healthy subjects with glabellar frown lines.
Interventions
DRUGEB-001 injection
DRUGPlacebo injection
Sponsors
Bonti, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Signed and dated IRB-approved informed consent form (ICF). 2. Men or women between the ages of 18 and 60, inclusive. 3. Subjects in good health as determined by medical history, physical and focused neurological examinations, clinical laboratory studies, electrocardiograms (ECGs), vital signs, and Investigator's judgement. 4. Presence of bilaterally symmetrical GL of moderate to severe rating at maximum frown, as measured using FWS by both the Investigator and subject prior to study treatment. 5. Subjects with sufficient visual acuity without the use of eyeglasses (contact lens use acceptable) to accurately assess their facial wrinkles as determined by Investigator's judgement. 6. Women of child bearing potential must not be pregnant, lactating, or planning to become pregnant during the study. 7. Women of non-childbearing potential must be either postmenopausal (at least 12 consecutive months of amenorrhea) or surgically sterile (e.g., tubal ligation, hysterectomy, etc.). 8. Women of childbearing potential agreeing to use dual methods of contraception from the day of dosing until 3 months afterwards. Female subjects using oral contraception must have initiated treatment at least 2 months prior to the day of dosing. 9. Male subjects with partner(s) of childbearing potential agreeing to use dual methods of contraception from the day of dosing until 3 months afterwards, and to no sperm donation from day of dosing until 3 months afterwards. 10. Willing and able to complete protocol requirements and instructions, which include completion of all required visits.
Exclusion criteria
1. Any condition that precludes a subject's ability to comply with study requirements, including completion of the study visits or inability to read, understand, and/or self-assess GL severity using FWS. 2. Any uncontrolled systemic disease or other medical condition. 3. Any medical condition that may put the subject at increased risk with exposure to botulinum toxin of any serotype, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other condition that might interfere with neuromuscular function. 4. Current or previous botulinum toxin treatment of any serotype. 5. Anticipated need for treatment with botulinum toxin of any serotype for any reason during the study (other than study treatment). 6. Known immunization or hypersensitivity to any botulinum toxin serotype. 7. Known allergy or sensitivity to any of the components of the study treatments, or any materials used in the study procedures. 8. Any of the following procedures or treatments occurring within the specified period prior to screening: * 3 months: Non-ablative resurfacing laser or light treatment, microdermabrasion, or superficial peels. * 6 months: Any facial cosmetic procedure with medium depth to deep facial chemical peels (e.g., trichloroacetic acid \[TCA\] and phenol), or mid facial or periorbital laser skin resurfacing. * 6 months: On topical retinoid therapy and/or topical hormone cream applied to the face, who have not been on a consistent dose regimen and are unable to maintain the same regimen for the study. * 12 months: Mid-facial or periorbital treatment with non-permanent soft tissue fillers. * 12 months: On oral retinoid therapy. 9. Prior periorbital surgery, facial lift (full face or mid face), brow lift, or related procedures (e.g., eyelid \[blepharoplasty\] and/or eyebrow surgery). 10. Prior mid face or periorbital treatment with permanent soft tissue fillers, synthetic implantation (e.g., Gore-Tex®), and/or autologous fat transplantation. 11. Marked facial asymmetry, dermatochalasis, deep dermal scarring, excessively thick sebaceous skin. 12. The inability to substantially lessen facial rhytides (fixed lines) even by physically spreading them apart, as determined by the Investigator. 13. Permanent make-up that would interfere with the assessment of facial wrinkles. 14. Subjects who, in the Investigator's opinion, are unable or unwilling to maintain their standardized skin care regimen throughout the study period. 15. Any eyebrow or eyelid ptosis at baseline as determined by the Investigator. 16. Infection or skin disorder at the injection sites. 17. History of facial nerve palsy. 18. Recent history (within 6 months of screening) of alcohol or drug abuse based on the Investigator's judgement. 19. Anticipated need for surgery or overnight hospitalization during the study. Current enrollment in an investigational drug or device study or participation in such a study within 30 days or 5 half-lives of the drug, whichever is longer, of entry into this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator's Assessment of GL Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS). | After single injection treatment up to 42 days | Subjects Achieving a 2 Grade Response At Maximum Frown On Any Study Day By Dose using the Facial Wrinkle Scale (FWS) The FWS is a four-point scale that indicates severity of GL as follows: 0 = none, 1 = mild, 2 = moderate, or 3 = severe. Each scale is a four-point photonumeric scale based on photographs incorporating each aspect to be evaluated in a stepwise manner. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Injection of placebo into five (5) 0.1 mL IM injections into glabellar area.
Placebo injection | 7 |
| EB-001 Dose 1 1st Dose in escalation paradigm.
Injection of active drug into five (5) 0.1 mL IM injections into glabellar area. | 5 |
| EB-001 Dose 2 2nd Dose in escalation paradigm.
Injection of active drug into five (5) 0.1 mL IM injections into glabellar area. | 5 |
| EB-001 Dose 3 3rd Dose in escalation paradigm.
Injection of active drug into five (5) 0.1 mL IM injections into glabellar area. | 5 |
| EB-001 Dose 4 4th Dose in escalation paradigm.
Injection of active drug into five (5) 0.1 mL IM injections into glabellar area. | 5 |
| EB-001 Dose 5 5thDose in escalation paradigm.
Injection of active drug into five (5) 0.1 mL IM injections into glabellar area. | 5 |
| EB-001 Dose 6 6th Dose in escalation paradigm.
Injection of active drug into five (5) 0.1 mL IM injections into glabellar area. | 5 |
| EB-001 Dose 7 7th Dose in escalation paradigm.
Injection of active drug into five (5) 0.1 mL IM injections into glabellar area. | 5 |
| Total | 42 |
Baseline characteristics
| Characteristic | Placebo | Total | EB-001 Dose 7 | EB-001 Dose 6 | EB-001 Dose 5 | EB-001 Dose 4 | EB-001 Dose 3 | EB-001 Dose 2 | EB-001 Dose 1 |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.4 years STANDARD_DEVIATION 8.48 | 47.9 years STANDARD_DEVIATION 10.29 | 42.6 years STANDARD_DEVIATION 10.26 | 53.2 years STANDARD_DEVIATION 4.66 | 45.4 years STANDARD_DEVIATION 11.39 | 50.8 years STANDARD_DEVIATION 6.5 | 52.2 years STANDARD_DEVIATION 9.36 | 39.4 years STANDARD_DEVIATION 16.13 | 52.0 years STANDARD_DEVIATION 5.43 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 7 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 30 Participants | 5 Participants | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 7 participants | 42 participants | 5 participants | 5 participants | 5 participants | 5 participants | 5 participants | 5 participants | 5 participants |
| Sex: Female, Male Female | 6 Participants | 38 Participants | 5 Participants | 5 Participants | 5 Participants | 4 Participants | 5 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 0 / 7 | 1 / 5 | 1 / 5 | 0 / 5 | 1 / 5 | 0 / 5 | 1 / 5 | 1 / 5 |
| serious Total, serious adverse events | 0 / 7 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Investigator's Assessment of GL Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS).
Subjects Achieving a 2 Grade Response At Maximum Frown On Any Study Day By Dose using the Facial Wrinkle Scale (FWS) The FWS is a four-point scale that indicates severity of GL as follows: 0 = none, 1 = mild, 2 = moderate, or 3 = severe. Each scale is a four-point photonumeric scale based on photographs incorporating each aspect to be evaluated in a stepwise manner.
Time frame: After single injection treatment up to 42 days
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Investigator's Assessment of GL Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS). | 1 Participants |
| EB-001 Dose 1 (1X) | Investigator's Assessment of GL Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS). | 0 Participants |
| EB-001 Dose 2 (3X) | Investigator's Assessment of GL Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS). | 0 Participants |
| EB-001 Dose 3 (9X) | Investigator's Assessment of GL Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS). | 2 Participants |
| EB-001 Dose 4 (12X) | Investigator's Assessment of GL Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS). | 3 Participants |
| EB-001 Dose 5 (16X) | Investigator's Assessment of GL Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS). | 2 Participants |
| EB-001 Dose 6 (21X) | Investigator's Assessment of GL Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS). | 4 Participants |
| EB-001 Dose 7 (28X) | Investigator's Assessment of GL Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS). | 4 Participants |