Evaluating the Performance and Safety of the Medical Device Plenhyage® in the Treatment of Dermal Tissue Defects

Study Overview
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Brief Summary
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The Research Question of the present study is the following: in a population of men and women presenting dermal tissue defects (scars, atrophic scars, depressed plaques, and lipodystrophy defects) will Plenhyage® significantly improve the appearance of treated areas, results observed after 4, 8 and 12 weeks?

Detailed Description
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Plenhyage® is a different type of dermal filler, an innovative course of polynucleotides to restore skin damage. The polynucleotide chain attracts water molecules, protecting against free radicals, acting as an absorber of hydroxyl radicals OH, which accumulate from stress, cell damage and UV rays. It also guarantees moisturising action and protection against free radicals. Nucleotides, natural fractions of DNA and RNA, are components of Plenhyage® with an antioxidant, protective effect. These characteristics allow Plenhyage® to be used as a temporary filler for subcutaneous areas to correct small defects in the dermal tissue due to lipodystrophies or the presence of fibrotic tissues as scars, caused by pathologies or trauma.

Official Title
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Open, Non-comparative, Multicentre Clinical Investigation to Evaluate the Performance and Safety of the Medical Device Plenhyage® (Polymerised Polynucleotides Dermal Filler) in the Treatment of Dermal Tissue Defects

Conditions
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Cicatrix, Lipodystrophy, Plaque

Intervention / Treatment
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* Device: Plenhyage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women with age ≥ 18 and ≤ 65 years. Patients presenting dermal tissue defects (scars, atrophic scars, depressed plaques, and lipodystrophy defects), seeking tissue augmentation treatment and willing to receive Polymerized Polynucleotides Filler. Patients who agree to discontinue any other dermatological treatment and procedures during the study. Patients willing to provide signed informed consent to clinical investigation participation. Patients able to communicate adequately with the Investigator and to comply with the requirements for the entire study. Exclusion Criteria: Use of aspirin and antiplatelet agents a week prior to treatment. Patients with history of allergy or hypersensitivity to polymerised polynucleotides or to other ingredients of the dermal filler or hypersensitivity skin reaction to the investigational device based on intradermal test results at visit 1. Patients with any dermal systemic pathologies, such as systemic lupus erythematosus, psoriasis, scleroderma etc.. Patients presenting bleeding disorders in the past or present. Patients taking or having indications for anticoagulant therapy. Use of concomitant treatments or procedures aimed to improve skin appearance over the last six months before the clinical investigation enrolment, such as chemical peeling, dermabrasion, laser resurfacing. Patients suffering from infectious diseases including herpes simplex virus infection, active hepatitis or human immunodeficiency virus. Patients suffering from active eczema, acne and keloids. Patients with any cutaneous manifested infection, disease or alteration. Patients at risk in term of precautions, warnings and contra-indications referred in the package insert of the clinical investigation device. Patients with any facial aesthetic surgery in the preceding 12 months before the clinical investigation enrolment Patients with any active irritation or inflammation in the target areas of injection. Patients who received botulinum toxin A injections in the face in the preceding 6 months. Patients unlikely to cooperate in the clinical investigation or to comply with the treatment or with the clinical investigation visits. Pregnant woman, lactating woman, and man or woman of childbearing potential who is planning a pregnancy or is unwilling to use appropriate methods of contraception* during the study. *Methods of contraception: hormonal contraceptive, intrauterine device or intrauterine system, double barrier method (condom with spermicide/diaphragm or cervical cap with spermicide), surgical sterilization (vasectomy, tubal ligation, etc.). Patients with illness, or other medical condition that, in the opinion of the Investigator, would compromise participation or be likely to lead to hospitalization during the study. Participation in an interventional clinical study or administration of any investigational agents in the previous 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a multi-center, open-label, non-randomized clinical investigation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plenhyage Thin<br>Sixteen patients will be administered Plenhyage® Thin for the treatment of minor -sized dermal tissue defects (scars, atrophic scars, depressed plaques, and lipodystrophy defects). | Device: Plenhyage<br>* Plenhyage® is an elastic, sterile, injectable, non-pyrogenic, re-absorbable gel made with polymerised polynucleotides (PDRN) of animal origin (fish). Due to its hydrophilic and polyanionic nature, PDRN binds water molecules, thereby filling intradermal spaces and making tissues firmer and more hydrated. The polynucleotide chain binds water molecules, has an anti-free radical action, and serves as a scavenger of hydroxyl radicals (OH), which accumulate under stress or due to foreign agents, such as UV radiation. Its hydration and anti-free radical activity help create the optimal environment for fibroblast growth, thereby restoring tissue elasticity. Plenhyage® is a colourless gel contained in a pre-filled, graduated, disposable, and sterile syringe with a Luer Lok adapter.<br>|
| Experimental: Plenhyage Medium<br>Sixteen patients will be administered Plenhyage® Medium for the treatment of medium-sized dermal tissue defects (scars, atrophic scars, depressed plaques, and lipodystrophy defects). | Device: Plenhyage<br>* Plenhyage® is an elastic, sterile, injectable, non-pyrogenic, re-absorbable gel made with polymerised polynucleotides (PDRN) of animal origin (fish). Due to its hydrophilic and polyanionic nature, PDRN binds water molecules, thereby filling intradermal spaces and making tissues firmer and more hydrated. The polynucleotide chain binds water molecules, has an anti-free radical action, and serves as a scavenger of hydroxyl radicals (OH), which accumulate under stress or due to foreign agents, such as UV radiation. Its hydration and anti-free radical activity help create the optimal environment for fibroblast growth, thereby restoring tissue elasticity. Plenhyage® is a colourless gel contained in a pre-filled, graduated, disposable, and sterile syringe with a Luer Lok adapter.<br>|
| Experimental: Plenhyage Strong<br>Sixteen patients will be administered Plenhyage® Strong for the treatment of major-sized dermal tissue defects (scars, atrophic scars, depressed plaques, and lipodystrophy defects). | Device: Plenhyage<br>* Plenhyage® is an elastic, sterile, injectable, non-pyrogenic, re-absorbable gel made with polymerised polynucleotides (PDRN) of animal origin (fish). Due to its hydrophilic and polyanionic nature, PDRN binds water molecules, thereby filling intradermal spaces and making tissues firmer and more hydrated. The polynucleotide chain binds water molecules, has an anti-free radical action, and serves as a scavenger of hydroxyl radicals (OH), which accumulate under stress or due to foreign agents, such as UV radiation. Its hydration and anti-free radical activity help create the optimal environment for fibroblast growth, thereby restoring tissue elasticity. Plenhyage® is a colourless gel contained in a pre-filled, graduated, disposable, and sterile syringe with a Luer Lok adapter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| POSAS score assessed by Investigator and patient | To evaluate the overall performance of the medical dermal filler Plenhyage® in treating dermal tissue defects (scars, atrophic scars, depressed plaques, and lipodystrophy defects) in terms of change in Patient and Observer Scar Assessment Scale (POSAS) score [Draaijers, 2004; van de Kar, 2005], assessed by Investigators and patients at 8 weeks ( 56 days) after the initiation of treatment, compared to Visit 1 (day 0) | 8 weeks | 
| POSAS score assessed by Investigator and patient | To evaluate the overall performance of the medical dermal filler Plenhyage® in treating dermal tissue defects (scars, atrophic scars, depressed plaques, and lipodystrophy defects) in terms of change in Patient and Observer Scar Assessment Scale (POSAS) score [Draaijers, 2004; van de Kar, 2005], assessed by Investigators and patients at 4 (28 days) after the initiation of treatment, compared to Visit 1 (day 0) | 4 weeks | 
| POSAS score assessed by Investigator and patient | To evaluate the overall performance of the medical dermal filler Plenhyage® in treating dermal tissue defects (scars, atrophic scars, depressed plaques, and lipodystrophy defects) in terms of change in Patient and Observer Scar Assessment Scale (POSAS) score [Draaijers, 2004; van de Kar, 2005], assessed by Investigators and patients at 12 weeks (84 days) after the initiation of treatment, compared to Visit 1 (day 0) | 12 weeks | 
| Investigator Global Assessment of Performance (IGAP) | To evaluate the global performance of product assessed by Investigator through photos taken at each visit (IGAP), at week 12 (day 84), compared to Visit 1 (day 0) | 12 weeks | 
| Adverse Event incidence | To evaluate the safety of the device through Adverse Event incidence assessed by Investigators at all visits and reported according to the current legislation | 12 weeks | 
| Serious Adverse Event incidence | To evaluate the safety of the device through Serious Adverse Event incidence assessed by Investigators at all visits and reported according to the current legislation | 12 weeks | 
| Adverse Device Event incidence | To evaluate the safety of the device through Adverse Device Event incidence assessed by Investigators at all visits and reported according to the current legislation | 12 weeks | 
| Serious Adverse Device Event incidence | To evaluate the safety of the device through Serious Adverse Device Event incidence assessed by Investigators at all visits and reported according to the current legislation | 12 weeks | 
| Device deficiency incidence | To evaluate the safety of the device through Device deficiency incidence assessed by Investigators at all visits and reported according to the current legislation | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Aesthetic Improvement Scale evaluated by the patient (GAIS) | To evaluate general appearance after treatment assessed by the patient at 4, 8 and 12 weeks (28, 56 and 84 days) using the Global Aesthetic Improvement Scale (GAIS) [Kim, 2016], [Kopera, 2015 - 2018], [McCall-Perez, 2011], [Savoia, 2015]. The scale evaluates the appearance from 1 (very much improved) to 5 (worse than original condition) . | 12 weeks | 
| Treatment satisfaction assessment by the patient | To assess the patient satisfaction at 4, 8 and 12 weeks (28, 56 and 84 days), providing their degree of satisfaction with the treatment on a four-point scale (very satisfied, satisfied, moderately satisfied, or not satisfied) | 12 weeks | 
| Investigator Global Assessment of Safety (IGAS) | To evaluate the global safety of product assessed by Investigator (IGAS), at week 12 (day 84), compared to Visit 1 (day 0), providing the safety on a four point scale from 4 meaning poor safety to 1 meaning very good safety. | 12 weeks | 
| Patient Global Assessment of Safety (PGAS). | To evaluate the global safety of product assessed by the patient (PGAS), at week 12 (day 84), compared to Visit 1 (day 0), providing the safety on a four point scale from 4 meaning poor safety to 1 meaning very good safety. | 12 weeks |