Evaluation of the Efficacy and Safety of the Dermal Filler for Female Intimate Area Hydration and Atrophy of the Vagina.

Study Overview
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Brief Summary
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The study is an open-label uncontrolled single-center study for the evaluation of the Performance characteristics (efficacy and safety) of the dermal filler MMG-23-04-2019 on the female genital area for the medicinal, functional and reconstructive indications.

Detailed Description
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The Dermal Filler is recommended for the female intimate areas, especially the internal area of the vagina (vaginal vestibule, introitus, vaginal walls, clitoris, G spot) for the following indications: vaginal dryness or discomfort, vaginal atrophy. The main functional ingredient is cross-linked hyaluronic acid of non-animal origin, produced through bacterial fermentation. The MMG-23-04-2019 is contained in pre-filled, graduated and disposable sterile syringe with Luer Lock adapter with 1 ml of net content and 20 mg/ml hyaluronic acid. The MMG-23-04-2019 has been classified as a Class III medical device under Annex IX of Directive MDD 93/42 EEC since it is a long-term, invasive and absorbable medical device.

Official Title
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An Open-Label Uncontrolled Single Centre Study for the Evaluation of the Performance Characteristics (Efficacy and Safety) of the Dermal Filler MMG-23-04-2019 (Hyaluronic Acid 2,0%) for Female Intimate Area Hydration and Atrophy of the Vagina.

Conditions
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Vaginal Atrophy, Vulvovaginal Signs and Symptoms, Dyspareunia, Urinary Incontinence

Intervention / Treatment
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* Device: MMG-23-04-2019


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subject aged ≥18; Subject presenting vaginal atrophy, dryness, dyspareunia or discomfort in the intimate area; Subject who presents no other type of pathology of the area to be treated; Subject who is willing to abstain from any cosmetic or surgical procedures in the treatment area during the clinical investigation; Subject who is willing to participate in all study related activities and who is available for the duration of their participation in the investigation for follow-up; Absence of a history of significant hypersensitivity to food and drugs or known sensitivity to hyaluronic acid; Clinically and anamnestic healthy individual; Arterial blood pressure (BP) (after 5 min. at rest in the supine position) systolic 90 - 140 mmHg and diastolic 50 - 90 mmHg; Heart rate (HR) (after 5 min. at rest in the supine position) over 50 beats/min and less than 90 beats/min; Respiratory rate between 12 - 24 breaths/min; An axillar body temperature of up to 37 degrees celsius; Clinical-laboratory examinations within the reference ranges or with no clinically significant abnormalities; Negative AIDS/HIV test; Negative pregnancy test for the women with reproductive potential; A reliable and acceptable method of contraception for the women of child-bearing potential: Signed written Informed Consent Form Exclusion Criteria: Subject with known sensitivity to hyaluronic acid or significant hypersensitivity to food and drugs; Subject with a history of vulvar cancer and/or previous regional radiotherapy; Subject with genital prolapse with a surgical indication or stress incontinence with a surgical indication; A subject who suffers from vaginism; Subject with genital bleeding of unknown origin; Subject with frequent or present active herpes simplex or herpes zoster local infection or active herpes simplex or herpes zoster infection in other sites; Subject with a history of frequent or active local dermatitis (of the injection site), vulvar scaly papilloma, mycosis; bacterial infection or laboratory tests indicating for such; A subject suffering from autoimmune diseases or who are undergoing treatment with immunosuppressors or immunotherapy; Subject with uncontrolled systemic diseases or who are undergoing current treatment with antihypertensives, steroid anti-inflammatory drugs anticoagulants, aspirin, major antidepressants; Pregnancy, postpartum period (6 months), lactation or post-lactation period (6 months); Absence of a reliable and effective method of contraception for a subject with childbearing potential; Subjects who are currently receiving another investigational treatment or who had participated in another clinical investigation within 30 days prior to study enrollment; A subject who suffer from another medical condition or who are receiving medication that in the Principal Investigator's judgment would prohibit the inclusion in the study; Subject with limited mental activity and consistent comprehension ability; sportsmen and individuals on strenuous physical loading; prisoners; Refusal to sign the Informed Consent Form.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MMG-23-04-2019<br>MMG-23-04-2019 is composed by sodium hyaluronate at concentration of 2% (20 mg/ml) with 1,4-Butanediol diglycidyl ether (BDDE) acting as a cross-linking agent, in aqueous solution at physiological pH. The filler of 1ml is administered once or twice depending on the individual necessity. | Device: MMG-23-04-2019<br>* The dermal filler MMG-23-04-2019 is applied to the female intimate area (intramucosal administration) of vaginal vestibule, vaginal walls, clitoris, G spot.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaginal Maturation Index (VMI) absolute change | Improvement in the properties of the vaginal wall, measured by the VMI. | From baseline to Day 60 (up to 8 weeks). | 
| Treatment-Emergent Adverse Events [Safety and Tolerability] | Frequency and severity of adverse events (AEs) and adverse device effect | From screening through study completion, an average of 60 days - daily. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the Gloria Bachmann Vaginal Health Index (VHI) | The VHI is a score formed by 5 parameters (vaginal elasticity, vaginal secretions, pH, epithelial mucous membrane, vaginal hydration). The final score defines the degree of atrophy in the genitourinary tract by assigning a single score to each parameter. The maximum possible score is 25, while the minimum possible score is 5. | From baseline to Day 30 (4 weeks) and Day 60 (up to 8 weeks). | 
| The absolute change in Visual Analogous Scale (VAS). | The absolute change in VAS, ranged between 0 (no pain) and 10 (worst possible pain), judged by the Principal Investigator. | From baseline to Day 30 (4 weeks) and Day 60 (up to 8 weeks). | 
| The absolute change in Visual Analogous Scale (VAS) | The absolute change in VAS ranged between 0 (no pain) and 10 (worst possible pain), judged by the subject. | From Day 0 to Day 30 (4 weeks) and Day 60 (up to 8 weeks). | 
| The change of the Female Sexual Function Index (FSFI) score. | The FSFI is a validated questionnaire to measure the sexual functioning of women. The score ranges between 2 (minimum) and 36 (maximum). | From Day 0 to Day 30 and Day 60 (up to 4 weeks and 8 weeks respectively). | 
| Subject satisfaction evaluated by the Global Impression of Improvement (PGI-I) questionnaire | The PGI-I is a transition single question scale, asking the patient to rate their urinary tract condition now, as compared with how it was prior to before beginning treatment on a scale from 1 (Very much better) to 7 (Very much worse) | From Day 30 (4 weeks) to Day 60 (up to 8 weeks). | 
| The change if the Nugent Score | The Nugent Score is a Gram stain scoring system for vaginal swabs to diagnose bacterial vaginosis, relying on scoring of individual types of organisms; a score of 0 to 10 is derived from a weighted combination of the following: large Gram-positive rods (lactobacilli; decrease in Lactobacillus scored as 0 to 4), small Gram-negative or Gram-variable rods (G. vaginalis or other anaerobes; scored as 0 to 4), and curved Gram-negative or Gram-variable rods (Mobiluncus spp.; scored as 0 to 2). | From baseline to Day 60 (up to 8 weeks). | 
| Viganal biopsy (optional) | Evaluation of the mitotic activity of the mucosa (Ki-67 proliferation marker - %). | From Day 0 up to Day 60 (up to 8 weeks). | 
| Participant's Questionnaire | To register the overall discomfort and satisfaction of the subjects. | From Day 0 to Day 30 and Day 60 (up to week 4 and 8 respectively). |