Proof of Concept Anti-ageing Clinical Study in Healthy Subjects

Study Overview
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Brief Summary
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The objective of this POC clinical study is to evaluate the moisturising effects on fine lines and wrinkles, texture, barrier function, hydration and elasticity delivered by 4 weeks of twice daily application of the test product on participants presenting visible signs of ageing.

Detailed Description
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Participants who meet all the inclusion/exclusion criteria will be randomised to one of three treatment groups: test product/positive control, test product/no treatment or positive control/no treatment at the baseline visit. Product application within treatment group will be further randomised to either the right or left side of the face. Participants will apply one of the assigned treatments to one side of the face (left or right) and another assigned treatment to the other side of the face as per the randomisation schedule. Participants will be instructed to apply the assigned treatments twice daily (morning and evening, approximately 8-12 hours apart) for 4 weeks (28 days).

Official Title
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A Proof of Concept (POC) Clinical Study to Evaluate the Appearance of Fine Lines and Wrinkles on a Developmental Cosmetic Moisturising Cream in Healthy Subjects Presenting Visible Signs of Ageing

Conditions
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Skin Aging

Intervention / Treatment
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* Other: Test product (Moisturising cream)
* Other: Positive control (Commercial market place moisturising cream)
* Other: No treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Demonstrates understanding of the study procedures, restrictions and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form Good general and mental health with, in the opinion of the investigator or medically qualified designee, no clinically significant and relevant abnormalities in medical history or upon physical examination Females of childbearing potential who are, in the opinion of the investigator, practising a reliable method of contraception. Adequate contraception is defined as abstinence, oral contraceptive, either combined or progestogen alone OR injectable progestogen OR implants of levonorgestrel OR estrogenic vaginal ring OR percutaneous contraceptive patches OR intrauterine device or intrauterine system OR double barrier method (condom or occlusive cap [diaphragm or cervical vault caps] plus spermicidal agent [foam, gel, film, cream, suppository]) OR male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that participant Willingness to actively participate in the study and to attend all scheduled visits Fitzpatrick phototype I-IV Visual Clinical Fitzpatrick Wrinkle Score 3- 6 in the eye (crow's feet) area on both sides of the face at screening and baseline Subjects with self-reported sensitive skin Exclusion Criteria: Women who are known to be pregnant or who are intending to become pregnant over the duration of the study Women who are breast-feeding Any history of significant dermatological diseases or conditions or medical conditions known to alter skin appearance or physiologic response (e.g.diabetes,) which could, in the opinion of the Investigator, preclude topical application of the investigational products and/or interfere with the evaluations Change in contraception within the last 3 months Presence of open sores, pimples, cysts, irritated skin, hairs or tattoos at the application site Active dermatosis (local or disseminated) that might interfere with the results of the study Considered immune compromised Currently using any medication which in the opinion of the investigator, may affect the evaluation of the study product, or place the subject at undue risk Use of the following topical or systemic medications: immunosuppressants, antihistamines, non-hormonal anti-inflammatory drugs, and corticosteroids up to 2 weeks before screening visit Intention of using any oral or topical steroids Regular use of inhaled steroids (occasional use is permitted) Regular use of topical anti-itch medications (occasional use permitted; the product should be applied with an applicator but not to the proposed application areas Use of any topical drug or medication in the proposed application areas Intention of being vaccinated during the study period or has been vaccinated within 3 weeks of the screening visit Currently receiving allergy injections, or received an allergy injection within 7 days prior to Visit 1, or expects to begin injections during study participation Blepharitis, conjunctivitis, uveitis Topical ocular treatment within the last month Aesthetic, cosmetic or dermatological treatment on the face within the last 3 months Intense sun exposure, Ultra Violet-treatments or tanning salon visit within the last 2 weeks Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients Participation in another clinical study (including cosmetic studies) or receipt of an investigational drug within 14 days of the screening visit Previous participation in this study Recent history (within the last 5 years) of alcohol or other substance abuse An employee of the sponsor or the study site or members of their immediate family A smoker

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Test product/ No treatment<br>Participants randomized to this arm will apply Test product at allocated sites and leave other sites untreated. | Other: Test product (Moisturising cream)<br>* Participants will be instructed to apply their assigned product to the randomly assigned side of the face, to include, the crow's feet area, cheek, forehead and chin twice daily (in the morning and evening).<br>Other: No treatment<br>* No treatment<br>|
| Other: Test product/ Positive control<br>Participants randomized to this arm will apply Test and positive product at allocated sites. | Other: Test product (Moisturising cream)<br>* Participants will be instructed to apply their assigned product to the randomly assigned side of the face, to include, the crow's feet area, cheek, forehead and chin twice daily (in the morning and evening).<br>Other: Positive control (Commercial market place moisturising cream)<br>* Participants will be instructed to apply their assigned product to the randomly assigned side of the face, to include, the crow's feet area, cheek, forehead and chin twice daily (in the morning and evening).<br>|
| Other: Positive control /No treatment<br>Participants randomized to this arm will apply Positive product at allocated sites and leave other sites untreated. | Other: Positive control (Commercial market place moisturising cream)<br>* Participants will be instructed to apply their assigned product to the randomly assigned side of the face, to include, the crow's feet area, cheek, forehead and chin twice daily (in the morning and evening).<br>Other: No treatment<br>* No treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Ra (a dermaTOP Parameter), of Test Product Treated Versus (vs.) Untreated Side at Day 29 | Using fringe projection and optical triangulation techniques, the 3D (three dimensional) surface structure of a designated investigational skin site on each side of the face was captured as an in vivo measurement using dermaTOP. From the captured 3D structure, roughness parameters were calculated. Ra is usually used for wrinkle assessments, representing the finer skin structure (Ra). Ra was the average deviation of the profile from the mean line (arithmetic mean of the absolute values of the point's heights). | At Baseline and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Ra (a dermaTOP Parameter), of Test Product Treated vs. Untreated Side at Day 15 | Using fringe projection and optical triangulation techniques, the 3D surface structure of a designated investigational skin site on each side of the face was captured as an in vivo measurement using dermaTOP. From the captured 3D structure, roughness parameters were calculated. Ra is usually used for wrinkle assessments, representing the finer skin structure (Ra). Ra was the average deviation of the profile from the mean line (arithmetic mean of the absolute values of the point's heights). | At Baseline and Day 15 | 
| Change From Baseline in Ra (a dermaTOP Parameter), of Positive Control Treated vs. Untreated Side at Day 15 and 29 | Using fringe projection and optical triangulation techniques, the 3D surface structure of a designated investigational skin site on each side of the face was captured as an in vivo measurement using dermaTOP. From the captured 3D structure, roughness parameters were calculated. Ra is usually used for wrinkle assessments, representing the finer skin structure (Ra). Ra is the average deviation of the profile from the mean line (arithmetic mean of the absolute values of the point's heights). | At Baseline, Day 15 and 29 | 
| Change From Baseline in Rz (a dermaTOP Parameter) at Day 15 and 29 | Using fringe projection and optical triangulation techniques, the 3D surface structure of a designated investigational skin site on each side of the face was captured as an in vivo measurement using dermaTOP. From the captured 3D structure, roughness parameters were calculated. Rz usually used for wrinkle assessments, representing the rough structure, such as wrinkles. Rz was an average of the 5 sub-profiles (peak to valley heights) local maximum. From each local profile the peak to peak height value is calculated; the average of the 5 peak to peak height values was Rz. | At Baseline, Day 15 and 29 | 
| Change From Baseline in Sa (dermaTOP Parameters) at Day 15 and 29 | Using fringe projection and optical triangulation techniques, the 3D surface structure of a designated investigational skin site on each side of the face was captured as an in vivo measurement using dermaTOP. The 3D skin surface profile was calculated from the position of the fringes in combination with the Gray values of each pixel. From the captured 3D structure, roughness parameters were calculated. Sa was the arithmetic average of the absolute (non- signed) heights of the topography points. Sa was the 3D Area -Equivalent of 2D profile roughness parameter Ra. | At Baseline, Day 15 and 29 | 
| Change From Baseline in Stm (dermaTOP Parameters), at Day 15 and 29 | Using fringe projection and optical triangulation techniques, the 3D surface structure of a designated investigational skin site on each side of the face was captured as an in vivo measurement using dermaTOP. The 3D skin surface profile was calculated from the position of the fringes in combination with the Gray values of each pixel. From the captured 3D structure, roughness parameters were calculated. Stm was an average of the 5x5 sub-areas (peak to valley heights) local maximum: The surface was virtually divided into 25 sub-surfaces (5 rows, 5 columns); from each local surface the peak to peak height value is calculated; the average of the 25 peak to height values was Stm. | At Baseline, Day 15 and 29 | 
| Change From Baseline in Clinical Fitzpatrick Wrinkle Score, at Day 15 and 29 | A blinded, trained and qualified examiner performed Clinical Fitzpatrick Wrinkle Score assessments by visually grading the crow's feet area under standard conditions of illumination. Fitzpatrick Wrinkle Scores range between 1-9 where 1-3= Fine wrinkles, 4-6= Fine to moderate depth wrinkles, a moderate number of wrinkles, 7-9= Fine to deep wrinkles, numerous lines, with or without redundant skin folds. Low value indicated better results. | At Baseline, Day 15 and 29 | 
| Change From Baseline in Instrumental Corneometer Values, at Day 15 and 29 | Measurement of Stratum Corneum (SC) hydration was performed by the electrical capacitance method with a Corneometer. The measuring principle was based on changes in the capacitance of the measuring head, functioning as a condensator. An electric field was created between gold conductors to enable the dielectricity of the SC to be measured. Because the dielectricity varies as a function of the skin's water content, the SC moisturisation was measured. Higher value of corneometery indicates high moisture content. | At Baseline, Day 15 and 29 | 
| Percent Improvement From Baseline in Skin Texture Rankings Based on Lay Grader Assessment of High Resolution Images at Day 29 | High resolution images of the left and right side of each participant's whole half-face were taken at baseline and Day 29. Each blinded image pair was randomly displayed on a color-calibrated screen and assessed by a panel of lay graders, who ranked each image based on texture, defined as pores, smoothness and unevenness, on a scale of: 1 = better; or 2 = worse (lower score indicated improvement). The total proportion of improvement (from all lay graders) on Day 29 than baseline is reported for this endpoint. | At Baseline and Day 29 | 
| Change From Baseline in Instrumental Cutometer Parameters R5, at Day 15 and 29 | The Cutometer measures elasticity of the upper skin layer using negative pressure which deforms the skin mechanically. Negative pressure was created in the device and the skin was drawn into the aperture of the probe and after a defined time released again. Inside the probe, the penetration depth was determined by a non-contact optical measuring system. The light intensity varies due to the penetration depth of the skin. The resistance of the skin to the negative pressure (firmness) and its ability to return into its original position (elasticity) was displayed as curves (penetration depth in mm/time) in real time during the measurement. This measurement principle provides information about the elastic and mechanical properties of the skin surface and enables objective quantification of skin ageing. R5 (net elasticity): the elastic portion of the suction part versus the elastic portion of the relaxation part. | At Baseline, Day 15 and 29 | 
| Change From Baseline in Instrumental Cutometer Parameter R7, at Day 15 and 29 | The Cutometer measures elasticity of the upper skin layer using negative pressure which deforms the skin mechanically. Negative pressure was created in the device and the skin was drawn into the aperture of the probe and after a defined time released again. Inside the probe, the penetration depth was determined by a non-contact optical measuring system. The light intensity varies due to the penetration depth of the skin. The resistance of the skin to the negative pressure (firmness) and its ability to return into its original position (elasticity) are displayed as curves (penetration depth in mm/time) in real time during the measurement. This measurement principle provides information about the elastic and mechanical properties of the skin surface and enables objective quantification of skin ageing. R7: Portion of the elasticity compared to the complete curve values. | At Baseline, Day 15 and 29 | 
| Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Day 15 and 29 | TEWL measuring principle was based on water vapour gradient determination between two pairs of sensors (temperature and relative humidity) placed at different distances perpendicularly to the skin. Measurements were taken in triplicate and then an average (mean) reading was calculated on the left and right Sub-ocular/ Cheek Area directly from the corner of the eyes onto the middle of the cheekbone. A decrease in TEWL corresponds to an improved skin barrier function. | At Baseline, Day 15 and 29 |