Evaluation of HA Dermal Fillers in the Treatment of Pathological Facial Lipoatrophy

A Prospective and Multicentric Investigation Evaluating the Clinical Safety of FASY F and FASY P Hyaluronic Acid Gel for the Treatment of Pathological Facial Lipoatrophy

Facial lipoatrophy (FLA) refers to the loss of adipose tissue and is manifested by flattening or indentation of convex contours of the face. Most frequently, the subcutaneous layer is affected and most common locations of adipose tissue loss are the cheeks, temples, preauricular, orbital or perioral and oral areas. Most common etiology for FLA is related to HIV. In 1998, first FLA was described in Subjects under highly active antiretroviral therapy (HAART). Currently, no specific treatment for FLA is known. For HIV-associated FLA, the European AIDS Clinical Society (EACS) recommends in prevention, the avoidance of some ART (Active Antiretroviral therapy) such as stavudine and zidovudine. In corrective purpose, the switch of ART is advisable as well as surgical intervention involving dermal fillers.

Different filling treatment options are available to treat volume defect on FLA Subjects including PolyLactic Acid (PLLA) (i.e.; Sculptra®), Calcium hydroxyapatite ( CaHa - i.e.: Radiesse®), autologous fat graft and hyaluronic acid (HA). Several studies shown promising results for the use of HA in this indication with good reconstructive and aesthetic outcomes, excellent safety profile and comparable to the autologous fat transfer treatment. HA fillers are described as voluming agents for treatment of FLA associated with fat wasting disorders, lasting at least 6 months but the persistent volumetric effect depends on HA crosslinking level and concentration.

The study is a pilot, prospective, multicenter, proof-of-concept clinical trial that aims to evaluate the safety and efficacy of FASY F and FASY P products for the treatment of FLA.

Inclusion Criteria:

1. Sex: male or female.

2. Age: 18 years and older.

3. If female of child-bearing potential, must have a negative urine pregnancy test before the first injection and use a reliable form of contraception for more than 12 weeks prior to screening and throughout the investigation.

   Note: to be considered females of non-child-bearing potential, females must be surgically sterile or postmenopausal or under highly effective birth control methods as: combined hormonal contraception (containing estrogens and progestogen) associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; sexual abstinence documented in medical history for at least 1 year.

4. In case of HIV:

   • HIV infection with a non-detectable viral charge (viral load <50 copies/mL) confirmed by a recent blood analysis.
   • Patient with platelet count greater than 50,000 cells/L by a recent blood analysis.

5. Patient with mild to moderate facial lipoatrophy based on "Ascher lipoatrophy Scale" scale (grade II to IV).

6. Patient, having given freely and expressly his/her informed consent.

7. Patient who is able to comply with the study requirements, as defined in the present clinical investigation protocole, at the Investigator's appreciation.

8. Patient being affiliated to a health social security system.

Exclusion Criteria:

1. Pregnant and breastfeeding women
2. Subject who is deprived of their freedom by administrative or legal decision.
3. Subject living in a social or sanitary establishment.
4. Major subject who is under guardianship or who is not able to express his consent.
5. Subject being in an exclusion period for a previous study or with a current or recent (<3 months) participation in another investigational study involving a drug or combined device with drug.
6. Subject who has scars, moles, sunburn, too many hairs, or other blemishes in the test area (face) which would interfere with the evaluation.
7. Subject suffering from a severe or progressive disease or any other pathology that may interfere with the evaluation of the study results: diabetes, autoimmune pathology, cardiac pathologies, hepatic deficiency, epilepsy, porphyria (other than HIV and related HIV disease).
8. Subject who has a known history of severe multiple allergies, angioedema or anaphylactic shock.
9. Subject with a known allergy or hypersensitivity to Hyaluronic Acid or local anesthesia (Lidocaine or anesthetics of the amide type or any of the excipients)
10. Subject with an acute inflammatory process or active skin disease, or related conditions, such as infection, psoriasis, rosacea, acne, blotches or other pathology near or on the injection sites with the potential to interfere with the study results or increase the risk of Adverse Events at the Investigator appreciation (other than HIV and related HIV disease).
11. Subject with a past history of severe streptococcal disease or an active streptococcus infection.
12. Subject predisposed to keloid or hypertrophic scarring.
13. Subject with a disorder that may impact wound healing such as connective tissue or immunosuppressive disorder (other than HIV and related HIV disease).
14. Subject with a history of precancerous lesions/skin malignancies on the injection sites.
15. Subject with history of hyper- or hypo-pigmentation on the face.
16. Subject with a known bleeding disorder or receiving medication that will likely increase the risk of bleeding during treatment, at the Investigator appreciation.
17. Subject having received high dose of Lidocaine (more than 200mg) and/or high dose of anesthetics structurally related to amide-type within the past week.
18. Subject having received chemotherapy agents, immunosuppressive medications or systemic corticosteroids within the past 3 months.
19. Patient having taken high-dose aspirin, anti-inflammatories, antiplatelet, thrombolytic during the week before the injection session.
20. Subject having received within the past 12 months any injections including nonpermanent fillers (e.g., Hyaluronic Acid, CaHA), mesotherapy or neurotoxin near or on the cheeks and/or cheekbones and/or infraorbital hollows or plan to undergo such treatment during the study.
21. Subject with prior permanent implant or treatment with non-HA or non-collagen filler near or on the cheeks and/or cheekbones and/or infraorbital hollows or plan to implement these products at any time during the study.
22. Subject having received within the past 6 months mesotherapy, resurfacing laser, photo modulation, intense pulsed light, radio frequency, photo-rejuvenation, dermabrasion, chemical peel, or other ablative or none ablative procedures near or on cheekbones and/or infraorbital hollows.
23. Subject with subcutaneous retaining structure on the face (meshing, threads, gold strand etc.).
24. Patient having received fat grafting within the past 12 months
25. Other condition preventing the subject to participate the study in the Investigator's opinion: subject deemed unreliable or incapable of understanding and complying with the study assessment or unrealistic expectations of treatment results.
26. Subject willing to perform any aesthetic treatment on the face other than treatment planned in the protocol during the study period.
27. Subject who have planned an intensive exposure to sunlight or UV-rays in the 2 weeks following injection.