Polymeric Microspheres vs Sculptra® in the Treatment of Moderate to Severe Nasolabial Folds

Study Overview
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Brief Summary
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This is a single-dose, randomized, double-blind, active-controlled, split-face, multiple centers, non-inferiority study. Approximately 50 nasolabial fold subjects will be enrolled. Each enrolled subject will be randomized equally into one of the following groups: Group 1: right face will be injected with PBF PLLA microsphere, and left face with Sculptra® Group 2: right face will be injected with Sculptra® and left face with PBF PLLA microsphere Subjects will be administrated on Visit 1 by applying PBF PLLA microsphere on one side of face and Sculptra® on the other.

Official Title
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A Controlled, Randomized, Double-Blinded, Intra-Subject, Multicenter, Prospective, Clinical Study to Investigate the Non-Inferiority Between the Polymeric Microspheres and Sculptra® in the Treatment of Moderate to Severe Nasolabial Folds

Conditions
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Nasolabial Fold Wrinkles

Intervention / Treatment
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* Device: PBF PLLA microsphere (injectable poly-L-lactic acid)
* Device: Sculptra®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant whose age is ≥ 18 and ≤ 65 years old. Participant who is able to read, understand, sign, and date a written informed consent form (ICF) before study participation at screening. Participant is able to understand and comply with protocol requirements and instructions and likely to complete the study as planned. Participant who has moderate to severe nasolabial folds on two sides of face, WAS Score ≥ 3. WAS Score is determined by investigator. Participant whose difference in WAS score of nasolabial folds on two sides of face ≤ 1. WAS Score is determined by investigator. Participant's skin condition is considered by Investigator suitable for the treatment of Poly-L-lactic Acid (PLLA). Exclusion Criteria: - 1. Participant who has previous tissue augmenting therapy, contouring or revitalization treatment in or near the treatment area prior to the Baseline visit. Treatment with collagen or hyaluronic acid (HA) in the last 12 months. Had facelift treatment (high intensity focused ultrasound, radio frequency, or thread) within 12 months. Had face laser treatment within 6 months. Had been treated with Calcium Hydroxyapatite (CaHA), PLLA or permanent (non-biodegradable). 2. Participant who has severe allergies with a history of severe reactions (anaphylaxis) or multiple severe allergies or has known/previous allergy or hypersensitivity to any of the PLLA, other constituents of PBF PLLA microsphere or Sculptra®, or drugs containing lidocaine such as Lidiprine Cream and its constituents. 3. Participant who has obvious defects, trauma, or scars near the treatment area. 4. Participant who has been diagnosed head cancer in the last 3 years. 5. Participant who has trauma, open wound, active skin disease or inflammation at the injection site. 6. Participant who has serious systematic disease that judged by Investigator which is not suitable for the treatment. 7. Participant who has connective tissue disease, bleeding disorders, active hepatitis, immune deficiency disease, disease such as cancer, stroke and/or myocardial infarction and on any immunosuppressive therapy. 8. Participant who previously had or have risks factors for hypertrophic scarring or keloid formation near the treatment area. 9. Participant who has used immune system suppression drugs, steroids, anti-inflammatory drugs, anticoagulant drugs, or aspirin within 7 days before treatment. 10. Female participant who is pregnant or lactating.

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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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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>right face will be injected with PBF PLLA microsphere, and left face with Sculptra® | Device: PBF PLLA microsphere (injectable poly-L-lactic acid)<br>* Poly-L-lactic acid (PLLA) is a collagen stimulator, helps restore the deep, underlying structure of the skin to diminish facial wrinkles. PLLA microparticles are absorbable for human body, and it works with human body within the deep dermis to help revitalize collagen production and help restore human skin's inner structure and volume. PLLA can rebuilt collagen strands begin gradually helping to restore facial volume and the look of fullness to wrinkles and folds.<br>Device: Sculptra®<br>* Sculptra®<br>|
| Experimental: Group 2<br>right face will be injected with Sculptra® and left face with PBF PLLA microsphere | Device: PBF PLLA microsphere (injectable poly-L-lactic acid)<br>* Poly-L-lactic acid (PLLA) is a collagen stimulator, helps restore the deep, underlying structure of the skin to diminish facial wrinkles. PLLA microparticles are absorbable for human body, and it works with human body within the deep dermis to help revitalize collagen production and help restore human skin's inner structure and volume. PLLA can rebuilt collagen strands begin gradually helping to restore facial volume and the look of fullness to wrinkles and folds.<br>Device: Sculptra®<br>* Sculptra®<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta of the WAS score between the Baseline and 26 weeks after treatment assessed by the Independent Evaluators of PLLA(PBF) versus Sculptra® | Wrinkle Assessment Scale (WAS): 0 No wrinkles; 1 Just perceptible wrinkle; 2 Shallow wrinkles; 3 Moderately deep wrinkle; 4 deep wrinkle, well-defined edges; 5 Very deep wrinkle, redundant fold | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall operation time during subcutaneous injection of PLLA(PBF) versus Sculptra® | To compare the operational smoothness for physicians between the two medical devices | First week from the Start of administration to the end of administration | 
| Delta of the WAS score assessed by the Investigator between each follow-up visit (13th, 26th, 39th and 52nd week post-administration) and the Baseline of PLLA(PBF) versus Sculptra® | Wrinkle Assessment Scale (WAS): 0 No wrinkles; 1 Just perceptible wrinkle; 2 Shallow wrinkles; 3 Moderately deep wrinkle; 4 deep wrinkle, well-defined edges; 5 Very deep wrinkle, redundant fold | 13th, 26th, 39th and 52nd week post-administration | 
| Delta of the WSRS score between the Baseline and 26 weeks after treatment assessed by the Independent Evaluators of PLLA(PBF) versus Sculptra® | Grade 1: No visible nasolabial fold; continuous skin line Grade 2: Shallow but visible nasolabial fold with a slight indentation; minor facial feature; the implant is expected to produce a slight improvement in appearance Grade 3: Moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected with injectable implant Grade 4: Very long and deep nasolabial folds; prominent facial feature; 2mm visible fold when stretched; significant improvement is expected with injectable implant Grade 5: Extremely deep and long nasolabial folds, detrimental to facial appearance; 2-4mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone | 26 weeks | 
| Delta of the WSRS score assessed by the Investigator between each follow-up visit (13th, 26th, 39th and 52nd week post-administration) and the Baseline of PLLA(PBF) versus Sculptra® | Grade 1: No visible nasolabial fold; continuous skin line Grade 2: Shallow but visible nasolabial fold with a slight indentation; minor facial feature; the implant is expected to produce a slight improvement in appearance Grade 3: Moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected with injectable implant Grade 4: Very long and deep nasolabial folds; prominent facial feature; 2mm visible fold when stretched; significant improvement is expected with injectable implant Grade 5: Extremely deep and long nasolabial folds, detrimental to facial appearance; 2-4mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone | 13th, 26th, 39th and 52nd week post-administration | 
| Percentage of responders based on the intra-individual improvement of at least one grade in the WAS score compared to baseline assessed by the Investigator of PLLA(PBF) versus Sculptra® | Wrinkle Assessment Scale (WAS): 0 No wrinkles; 1 Just perceptible wrinkle; 2 Shallow wrinkles; 3 Moderately deep wrinkle; 4 deep wrinkle, well-defined edges; 5 Very deep wrinkle, redundant fold | 13th, 26th, 39th and 52nd week post-administration | 
| Percentage of responders based on the intra-individual improvement of at least one grade in the WSRS score compared to baseline assessed by the Investigator of PLLA(PBF) versus Sculptra® | Grade 1: No visible nasolabial fold; continuous skin line Grade 2: Shallow but visible nasolabial fold with a slight indentation; minor facial feature; the implant is expected to produce a slight improvement in appearance Grade 3: Moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected with injectable implant Grade 4: Very long and deep nasolabial folds; prominent facial feature; 2mm visible fold when stretched; significant improvement is expected with injectable implant Grade 5: Extremely deep and long nasolabial folds, detrimental to facial appearance; 2-4mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone | 13th, 26th, 39th and 52nd week post-administration | 
| Number of subjects scored either 'Much Improved' or 'Improved' on GAIS evaluated by the Investigator for PLLA(PBF) versus Sculptra® |  | 13th, 26th, 39th and 52nd week post-administration | 
| Subject's satisfaction score (Subjective 5-point scale with 1 being 'very satisfied' and 5 being 'very dissatisfied') of PLLA(PBF) versus Sculptra® |  | 13th, 26th, 39th and 52nd week post-administration |