Safety and Efficacy Study of Lidocaine Mixed Hyaluronate on Nasolabial Folds Correction

Study Overview
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Brief Summary
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This clinical trial is a double-blind, randomized, within-subject controlled, 2-armed, single-center study sponsored by SciVision Biotech Inc. and approved by National Taiwan University Hospital Research Ethics Committee. The aim of this post-marketing study is to evaluate the safety and efficacy of Hya-Dermis mixed with lidocaine, as well as the effectiveness of corrections of Hya-Dermis mixed with lidocaine. Accounting for potential loss to follow-up, the minimum enrollment was statistically determined to be 40 patients. The study was estimated to be held one and half year including a 0-2 weeks screening period, a day of treatment, and follow-up at month 1, 3, 6, 9, 12. Patient informed consent forms will be obtained before the treatment. A pre-treatment photograph, nasolabial folds (NLF) severity scale scores, and individual aesthetic satisfaction will be the baseline. Two sets of randomized numbers are used, patient numbers and treatment numbers. Participants with odd patient numbers will be assigned to nasolabial group and those with even patient numbers will be assigned to nasolabial&cheekbone group. Participants receive experiment treatment (Hya-Dermis mixed with lidocaine) in one side and control treatment (Hya-Dermis mixed with normal saline) in the other side of the face randomly depending on the treatment numbers. Both physicians and participants are only blind to the treatment assignment. 30 minutes after the injection, a post-photograph will be used to evaluate NLF severity scale scores and global aesthetic improvement scale (GAIS) by physicians. A questionnaire including the Visual Analog Scale (VAS) of pain during the treatment and individual aesthetic satisfaction will be collected from patients. The effectiveness analyses compare NLF severity scale scores and GAIS based on photograph records from physicians, as well as participant questionnaires for each group on every visit. The safety assessment evaluates any recorded adverse events following the device treatment.

Official Title
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Safety and Efficacy Study of Hya-Dermis Mixed With Lidocaine Injection for the Improvement of Nasolabial Folds

Conditions
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Nasolabial Folds Correction, Pain

Intervention / Treatment
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* Drug: Lidocaine
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be 30 to 60 years of age and of any sex and willing to receive nasolabial folds correction by intradermal injection procedures Have ability to understand and comply with the study requirements Have approximately symmetrical nasolabial folds with a nasolabial folds severity score of 2-3 and the score difference between two sides is less 1 Agree to refrain from undergoing other anti-wrinkle treatments in the injective areas 12 months after the injections. If female of child-bearing potential, not be breastfeeding, have a negative urine pregnancy test on the treatment day and agree to use any approved contraceptives or medically acceptable method of birth control throughout the study Be willing to provide written informed consent prior to any procedures Exclusion Criteria: Have history or active dermal diseases, inflammation, or any related disease, such as infection, psoriasis, and herpes. Have history of coagulation defect diseases and still take aspirin, other anti-clotting, or blood activating medications 1 week before the treatments Had permanent or semi-permanent implantation on nasolabial areas Had dermal-related surgeries history (for example, laser, chemical dermabrasion, fraxel laser, thermocool) 6 months before the treatments. Had facial wrinkles and folds corrections (for example, botox or other dermal fillers) 6 months before the study starts Have a known history of allergic reactions like hypersensitivity to hyaluronic acid Have a known history of allergic reactions to lidocaine other local anesthesia Have poor compliance with the study or follow-up schedule

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Normal saline<br>Participants will be randomly assigned to nasolabial or nasolabial&cheekbone group and receive control treatment (20mg/ml hyaluronic acid mixed with 0.175 ml normal saline) in one side of the face. | Drug: Normal Saline<br> <br> |
| Active Comparator: Lidocaine<br>Participants will be randomly assigned to nasolabial or nasolabial&cheekbone group and receive experiment treatment (20mg/ml hyaluronic acid mixed with 0.175 ml 2% lidocaine) in one side of the face. | Drug: Lidocaine<br>* Xylocaine is a 2 % lidocaine hydrochloride contained liquid anesthesia<br>* Other names: Xylocaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Visual Analog Scale | A quantification of the severity of pain experienced by individuals during the treatments. A scale of 100 mm horizontal line will be labeled by participants to assess pain on both sides of the injected areas 30 minutes after the treatment. The one on the extreme left (0) represents painless while the one on the extreme right (100) is set as the most pain could be imagined by participants. | 30 miuntes post-treatment | 
| Adverse events report | Any adverse events and abnormal physical parameters or reports occurred and disappeared should be monitored throughout the trial. The records should be assessed and keep on track of the severity of individual adverse events and correlation with the treatment. Severity assessment: To assess the level of severity by rating 0 (none), 1 (mild), 2 (median), and 3 (sever). Correlation assessment: Physicians evaluate the impact of adverse events for each individual and determine their causality of the treatment. Based on the correlation with the treatment, giving score 0 (no correlated), 1 (low correlated), 2 (suspected correlated), 3 (most likely correlated). Adverse events tracking: Any adverse events should be reported to the physicians by participants. Physicians keep following up adverse events experienced participants until the event disappeared or the symptoms stabilized. | From date of treatment to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nasolabial folds (NLF) severity scale | Based on Skin Aging Atlas: Volume 2, Asian type photographs13, taking gender and NLF into consideration to quantify the degree of NLF severity. A validated 8-point photographic scale scored the severity grade from 0 (absent) to 7 (extreme) will be used to assess the severity of NLF at baseline, 30 minutes post-treatment, and every follow-up at 1, 3, 6, 9, 12 months. | From the baseline, 30 minutes post-treatment, to every follow-up at 1, 3, 6, 9, 12 months | 
| Global aesthetic improvement scale (GAIS) | To quantify the level of overall aesthetic improvement 30 minutes after treatments and every follow-up at 1, 3, 6, 9, 12 months. A scale from 1 to 5 represent worse (1), no change (2), improved (3), much improved (4), and very much improved (5). | 30 minutes post-treatments and follow-ups at 1, 3, 6, 9, 12 months | 
| Aesthetic satisfaction questionnaire | Subjects subjectively assessed overall satisfaction of general appearance toward the effectiveness of the treatment by rating 1 (not at all satisfied), 2 (not satisfied), 3 (neither satisfied nor dissatisfied), 4 (somewhat satisfied), and 5 (highly satisfied). | From the baseline, 30 minutes post-treatment, to every follow-up at 1, 3, 6, 9, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hya-Dermis mixed with lidocaine on reducing pain