Clinical Study Evaluating the Safety and Effectiveness of The Tixel Fractional System in The Treatment of Periorbital Wrinkles

Study Overview
=================
Brief Summary
-----------------
A Prospective, Multicenter, Single-Arm Clinical Study of 51 study subjects who are seeking a procedure to reduce the appearance of the peri-orbital wrinkles. Up to 5 investigational centers in Israel and the United States will participate in the recruitment. Each study subject will receive four (4) treatments with Tixel in a monthly interval. Follow-up will occur 1 month and 3 months following last treatment.

Detailed Description
-----------------
A Prospective, Multicenter, Single-Arm Clinical Study of 51 subjects who are seeking a procedure to reduce the appearance of the periorbital wrinkles, and meet study eligibility criteria, and have provided informed consent will be enrolled in the study. Up to 5 investigational centers in Israel and the United States will participate in the recruitment. Each study subject will receive 4 treatments with Tixel in a monthly interval. Follow-up will occur at 1 month and 3 months following the last treatment. The clinic visits will be as follow: Baseline (1st tx) Phone-call visit (3 days after the first treatment) 4wk (2nd tx) 8wk (3rd tx) 12wk (4th tx) 4 weeks after the last treatment (1st FU) 12 weeks after the last treatment (2nd FU= 3 months FU, primary endpoint and study completion visit) Primary Efficacy Endpoint is the comparison of the proportion of subjects with a ≥ 1-score improvement on the FWCS at the 3-month visit compared to baseline as determined by at least 2 out of 3 blinded Independent Photographic Reviewers. Primary Safety Endpoint is the evaluation of related adverse events up to the 3-month visit after treatment.

Official Title
-----------------
A Prospective, Multicenter, Single-Arm Clinical Study Evaluating the Safety and Effectiveness of The Tixel Fractional System in The Treatment of Periorbital Wrinkles

Conditions
-----------------
Wrinkle, Periorbital, Tixel 2, Fractional, Resurfacing

Intervention / Treatment
-----------------
* Device: Tixel 2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female 35-70 years old diagnosed with clinically evident fine (mild) to moderate depth periorbital wrinkling Willingness and ability to comply with all required study activities including returning for follow-up visits and protocol requirements. The subject is able to provide written informed consent and perform the study's activities according to HIPAA guidelines and/or Israeli law, depending on each specific study site. Fitzpatrick wrinkle score of 3-7 in the peri-orbital areas per the treating investigator and clinically noticeable wrinkles in the treating area. Stable body weight during the study period. Skin Type I - V as per Fitzpatrick Skin Scale Exclusion Criteria: Past treatment with Tixel device. The subject may not undergo treatment by the Tixel device according to the device's contra-indications for use, as defined in the User Manual and in the Instructions for Use and by any other labeling of the device. Subjects who, in the investigator's opinion, have a history of poor cooperation, noncompliance with medical treatment, or unreliability. Female subjects who are pregnant, or planning to become pregnant, or have given birth less than 3 months ago or are lactating. Subjects with significant exposure to critical amounts of ultraviolet light (Sun-tan). Subjects who have had the following treatments: a cosmetic procedure to improve peri-orbital rhytides (i.e. periorbital or eyelid/eyebrow surgery, brow lift, CO2/Erbium/similar laser/fractional resurfacing, radiofrequency treatment) within 12 months prior facial treatments with laser, surgical, chemical or light-based facial treatments within the previous 12 months, over the periorbital area including botulinum toxin injections, microdermabrasion or prescription level glycolic acid treatments. Injectable filler in cheeks (mid face) temples and in the upper face area to be treated within 12 months of investigation. Any subject who have visible scars or other visible changes over the treated areas that may affect evaluation of response and/or quality of photography. Subjects with any type of active cut, wound, inflammation, lesion (benign, premalignant or malignant) or active bacterial, viral, fungal, or herpetic infection on the skin on the designated treatment sites or in close proximity to it. Existing or history of the following (when discussing skin conditions, refers only to the periorbital sites): skin malignancy, or any diagnosis of suspected malignancy Collagen or vascular or bleeding disease Immunosuppression or autoimmune disease Erythema with or without blistering History of post inflammatory hyperpigmentation. Active Acne Vulgaris, HSV-1, or any existing skin condition/disease that in the investigator's opinion would interfere with the evaluation of the safety of the study treatment and evaluation. Any skin pathology which can induce bullous lesions, urticaria, or demonstrate a Koebner phenomenon (psoriasis, lichen planus, etc.). Any disease that inhibits pain sensation History of keloid formation, or hypertrophic scarring Conditions affecting healing rate (i.e. diabetes mellitus I or II, vascular condition, etc.) neuromuscular disorders Subjects who have used, within 30 days, any medication that can cause dermal hypersensitivity or affect skin characteristics over the treated area (i.e. topically applied Retinoids, Hydroquinone, Chemical peel of any strength: glycolic acid, lactic acid, salicylic acid) Subjects who have used, systemic treatment which may induce dyspigmentation, such as amiodarone, clofazinmine, minocycline or chloroquine. Subjects currently taking or have taken an oral retinoid in the past six months; Subjects currently taking long-term oral steroid treatment. Concurrent therapy that, in the principal investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study treatment. Subjects who anticipate the need for major surgery or overnight hospitalization during the study that can affect the study schedule or treatment evaluation. Enrollment in any active study involving the use of investigational devices or drugs. Any other cause per the principal investigator's discretion.

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All participants will undergo treatment with Tixel 2 Device - 4 treatments, 4 weeks apart and 2 Follow Up visits
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tixel 2<br>Tixel 2 Treatment, 4 treatment sessions, followed by 2 Follow up sessions, 1and 3 months after last treatment visit. Subject would be questioned about pain level, subjective dountime assessment and subjective response assessment. Images would be taken at baseline and in Follow-Up visits | Device: Tixel 2<br>* Thermo-mechanical technology for fractional treatment of human skin. Dermal heating and coagulative effect that occur during the treatment session provide dermal remodeling and collagen restructuring that promote wrinkles appearance improvement.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Adverse Events report | Evaluation of related adverse events up to the 3-month after treatment visit. | Up to 8 months | 
| Effectiveness using Fitzpatrick Wrinkle Classification Scale (FWCS) - Blinded | Comparison of the proportion of subjects with a ≥ 1-score improvement on the Fitzpatrick Wrinkle Classification Scale (FWCS) at the 3-month visit compared to baseline as determined by at least 2 out of 3 blinded Independent Photographic Reviewers. The FWCS is a clinically validated assessment tool used to assess skin wrinkle severity and elastosis on a scale from 1 through 9, where the lower score is considered better. | Up to 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness using Fitzpatrick Wrinkle Classification Scale (FWCS) - Unblinded | Assessment of improvement using Fitzpatrick Wrinkle Classification Scale (FWCS) at each visit compared to baseline by the handling physician. The FWCS is a clinically validated assessment tool used to assess skin wrinkle severity and elastosis on a scale from 1 through 9, where the lower score is considered better. | Up to 8 months | 
| Effectiveness using GAIS - Global Aesthetic Improvement Scale Assessment - Unblinded | Assessment of improvement using Global Aesthetic Improvement Scale Assessment at each visit compared to baseline by the handling physician. Rating: 1) expectational improvement; 2) very improved patient; 3) Improved patient; 4) Unaltered patient; 5) Worsened patient | Up to 8 months | 
| Evaluation of the pain and discomfort | Evaluation of the pain and discomfort of the treatment as reported by the subject on a visual analog scale (VAS). Scoring will consist of making a mark on a 10-points scale. Each line will be awarded a score of 0 - 10 according to the level of pain when 0 is no pain and 10 is the maximum pain possible. | Up to 6 months | 
| Subject Subjective Downtime Assessment | Evaluation of the period of time following the procedure during which the subject felt unable/unwilling to go out in public due to edema and/or erythema | Up to 6 months | 
| Patients' Reported Outcomes | Subject Satisfaction Questionnaire and GAIS - Global Aesthetic Improvement Scale Assessment. Rating: 1) expectational improvement; 2) very improved patient; 3) Improved patient; 4) Unaltered patient; 5) Worsened patient | Up to 8 months |