A Study to Evaluate The Impact on Skin Quality Attributes by Juvederm® Volite Injection on Healthy Volunteers

Study Overview
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Brief Summary
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To evaluate the impact on skin quality attributes, including physical measurements and gene and protein expression (histological and genomic analysis), following administration of Juvéderm® VOLITE in the volar forearms of healthy volunteers.

Official Title
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Prospective, Open-Label Study, to Evaluate The Impact on Skin Quality Attributes by Juvederm® Volite Injection on Healthy Volunteers

Conditions
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Healthy Adults, Skin Enhancement

Intervention / Treatment
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* Device: Juvederm® VOLITE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants Participants with Fitzpatrick skin type II or III Participant willing to receive Juvéderm® VOLITE in the forearms and agrees to complete all study required procedures, including having 6 cutaneous punch biopsies taken in the forearms and blood drawn (Human immunodeficiency virus [HIV], B and C hepatitis analysis at screening) Written informed consent and data privacy consent obtained Exclusion Criteria: Pregnant or nursing woman or planning a pregnancy during the study Participant participating to another research on human beings or being in an exclusion period for a previous study Intensive exposure to sunlight or ultraviolet (UV)-rays within the previous month and foreseen during the study Participant having other resorbable filling product injections, a laser treatment, an ultrasound-based treatment, radiation treatment, a dermabrasion, a surgery, a deep chemical peeling or other ablative procedure on the studied zones within the past 12 months prior to study start Participant with subcutaneous retaining structure on the studied zones (meshing, threads, gold strand) Participant having received injections of permanent or semi-permanent filling products in the studied zones Participant under anti-coagulant treatment or treatment liable to interfere with the healing process or hemostasis, during the previous month and during the study Participant receiving or is planning to receive anti-inflammatory drugs (oral/injectable corticosteroids or Nonsteroidal anti-inflammatory drugs (NSAIDs), e.g., aspirin, ibuprofen), or other substances known to increase coagulation time (herbal supplements with garlic or ginkgo biloba, etc) for 10 days prior to study treatment and 3 days after Participant under immunosuppressive therapy

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 50 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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Juvéderm® VOLITE<br>Participants received Juvéderm® VOLITE, intradermal injection on a zone of 8 centimeter (cm) x 4 cm (32 cm^2) of the volar left forearm on Day 0. The dose to be injected was decided by the investigator as per the Directions for Use. A maximum of 1 milliliter (mL) was injected on the zone treated. | Device: Juvederm® VOLITE<br>* 1 mL of Juvéderm® VOLITE contains hyaluronic acid gel 12.0 milligram (mg), lidocaine hydrochloride 3.0 mg in a phosphate buffer pH 7.2 q.s. 1 mL (or gram).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Skin Hydration as Measured by MoistureMeterD® 0.5 mm | Skin hydration was measured using MoistureMeterD® XS (for epidermis and dermis), a non-invasive probe which measures the dielectric constant of the skin at a depth of 0.5 mm. 5 measurements were done on the same zone and the average value was calculated, expressed as tissue dielectric constant (TDC). The TDC is directly proportional to the amount of water in the tissue. A positive change from Baseline indicates better skin hydration. Values were obtained from a mixed analysis of variance (ANOVA) model. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline [Day 0 (D0)] to Days 28 (D28) and 84 (D84) | 
| Change From Baseline in Skin Hydration as Measured by MoistureMeter D® 1.5 mm | Skin hydration was measured using MoistureMeter D® S15 (for epidermis and dermis), a non-invasive probe which measures the dielectric constant of the skin at a depth of 1.5 mm. 5 measurements were done on the same zone and the average value was calculated, expressed as TDC. The TDC is directly proportional to the amount of water in the tissue. A positive change from Baseline indicates better skin hydration. Values were obtained from a mixed ANOVA model. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Skin Hydration as Measured by Corneometer® | Corneometer® measures the hydration level of the superficial skin surface (epidermis). The measurement is based on capacitance measurement of a dielectric medium in this case skin. It uses fringing field capacitance sensors to measure the dielectric constant of the skin. The dielectric constant of skin will change with water content. This allows for any changes in skin hydration to be measured by the precision measuring capacitor. These changes in water content of the stratum corneum are converted into arbitrary units of hydration. 5 measurements were done on the same zone and average value was calculated. Values were obtained from a mixed ANOVA model and expressed in arbitrary units. A positive change from Baseline indicates better skin hydration rate. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Skin Elasticity Parameters: Uf: Final Deformation (Firmness), Ue: Immediate Extensibility, Ur: Immediate Retraction (Tonicity), Ua: Total Recovery of the Initial State as Measured by Cutometer ® | Skin elasticity was measured by a Cutometer ® which uses an in vivo non-invasive method to evaluate biological extensibility and elasticity variations. The various parameters analysed were Uf: final deformation (firmness), Ue: immediate extensibility, Ur: immediate retraction (tonicity), Ua: total recovery of the initial state. 2 measurements were done on the same zone and the average value was calculated. Values were obtained from a mixed ANOVA model. A Negative change from Baseline indicates firmer skin. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Relative Parameters of Skin Elasticity: Q1, Q2, Q3 as Measured by Cutometer ® | The parameters evaluated were: Elastic Recovery (Q1)=elastic recovery area (QE)/maximum recovery area (QO), Viscous Recovery (Q2)=viscous recovery area (QR)/maximum recovery area (QO) and Viscoelastic Recovery (Q3)= (QE+QR)/QO. 2 measurements were done on the same zone and the average value was calculated. Values were obtained from a mixed ANOVA model. A negative change from Baseline in Q1 and Q2 indicates decreased skin elasticity. A positive change from Baseline in Q3 indicates decreased skin elasticity. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Number of Participants With at Least One Treatment-emergent Adverse Event (AE) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A treatment-emergent AE is an AE that occurs or worsens after a participant receives study drug. | First dose of study treatment to end of the study (Up to 9 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Skin Elasticity as Measured by Elastimeter® | Instant skin elasticity was measured with Elastimeter® and defines the skin elasticity determined as a resistance against deformation caused by the Elastimeter® probe on the skin surface. 3 measurements were done on the same zone and the average value was calculated. The values were expressed in Newton/meter. Higher values of ISE indicate higher skin elasticity. A positive change from Baseline indicates increased skin elasticity. Values were obtained from a mixed ANOVA model. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Skin Thickness as Measured by Skin Scanner® | Skin thickness was measured as the average thickness of the epidermis and dermis (in mm) using SkinScanner®, a high frequency echograph. Values were obtained from a mixed ANOVA model. A positive change from Baseline indicates increased skin thickness. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Skin Density as Measured by Skin Scanner® | Skin density was measured as the percentage of echogenic surface using SkinScanner®, a high frequency echograph. Values were obtained from a mixed ANOVA model. A positive change from Baseline indicates increased skin density. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Skin Roughness as Measured by Vivosight OCT® | Skin roughness was measured by Vivosight optical coherence tomography (OCT®) system which is used to obtain high resolution imaging of skin sub-structures and vascular networks. The skin roughness parameters from the images included Ra and Rz. Ra is a measure of the average length that is between peaks and valleys. Rz helps measure the vertical distance between the highest peak and the lowest valley. Values were obtained from a mixed ANOVA model. A negative change from Baseline indicates decreased skin roughness. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Epidermal Thickness as Measured by Vivosight OCT® | Epidermal thickness is a skin density parameter measured by Vivosight OCT® system used to obtain high resolution imaging of skin sub-structures and vascular networks. Values were obtained from a mixed ANOVA model. A positive change from Baseline indicates increased epidermal thickness. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Optical Attenuation Coefficient (OAC) as Measured by Vivosight OCT® | OAC is a skin density parameter measured by Vivosight OCT® system used to obtain high resolution imaging of skin sub-structures and vascular networks. It analytically describes the reduction of OCT signal intensity with increasing depth-in-tissue. Values were obtained from a mixed ANOVA model. A positive change from Baseline indicates increased skin density. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Plexus Depth as Measured by Vivosight OCT® | Plexus depth is a skin vascularity parameter and was measured by Vivosight OCT® system which is used to obtain high resolution imaging of skin sub-structures and vascular networks. Values were obtained from a mixed ANOVA model. A negative change from Baseline indicates decreased plexus depth. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Vessel Diameter as Measured by Vivosight OCT® | Vessel diameter is a skin vascularity parameter and was measured by Vivosight OCT® system which is used to obtain high resolution imaging of skin sub-structures and vascular networks. Values were obtained from a mixed ANOVA model. A positive change from Baseline indicates increased vessel diameter. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Vessel Density as Measured by Vivosight OCT® | Vessel density is a skin vascularity parameter and was measured by Vivosight OCT® system which is used to obtain high resolution imaging of skin sub-structures and vascular networks. A positive change from Baseline indicates increased vessel density. Values were obtained from a mixed ANOVA model. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in 300 μm Density as Measured by Vivosight OCT® | 300 μm density is a skin vascularity parameter and was measured by Vivosight OCT® system which is used to obtain high resolution imaging of skin sub-structures and vascular networks. Values were obtained from a mixed ANOVA model. A positive change from Baseline indicates increased 300 μm density. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Skin Brightness Index as Measured by Glossymeter® | Skin brightness index was measured using Glossymeter®. 3 measurements were done on the same zone and the average value was calculated. Values were expressed in Glossymeter Units. Values were obtained from a mixed ANOVA model. Higher glossymeter values indicate higher skin brightness. A positive change from Baseline indicates increased skin brightness. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Skin Colour as Measured by Spectrophotometer® | Skin colour was measured by Spectrophotometer®. It converts colours perceived by man to a digital code composed of three parameters: L*: for clarity (from dark to light) a*: for the green-to-red spectrum b*: for the blue-to-yellow spectrum; a* and b* are chrominance parameters, L* is a luminance parameter. Higher values of a*, b*and L* indicates 'skin more red', 'skin more yellow' and 'skin clearer'. Values were obtained from a mixed ANOVA model and expressed in arbitrary units. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Individual Typological Angle (ITA°) as Measured by Spectrophotometer® | Individual typological angle (ITA°), defines the skin pigmentation degree of a participant with taking into account the skin clarity (L*) and the melanin parameter (b*). 3 measurements were done on the same zone and the average values were calculated. Values were obtained from a mixed ANOVA model and expressed in degree (°). Higher values of ITA° indicates 'skin less pigmented'. A positive change from Baseline indicates less pigmented skin. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Change From Baseline in Skin Melanin Index as Measured by Mexameter® | Melanin index measured with Mexameter® defines the skin pigmentation related to melanin content in the skin. Measurements are performed by the application of a probe to the skin surface. The probe has a 5 mm aperture that emits radiations. These radiations are reflected by the skin and captured back by the same probe. The results are expressed as an index value for each parameter in arbitrary units from 0 to 999. 3 measurements were done on the same zone and the average value was calculated. Values were obtained from a mixed ANOVA model. A negative change from Baseline indicates less pigmented skin. The data is presented for area treated with Juvéderm® VOLITE and non-treated area in the same participants. | Baseline (D0) to D28 and D84 | 
| Number of Participants With Injection Site Reactions (ISR) | ISRs are reactions that occur after injection of the study drug. The following ISRs: Redness/Erythema, Pain/Tenderness, Induration, Swelling/Oedema, Lumps/Bumps, Bruising/Hematoma, Itching, Discoloration/Pigmentation were reported as None, Mild, Moderate or Severe. Only those categories reported for at least 1 participant are reported. | Day 0 |