Emervel Classic Lidocaine Versus Juvederm® Ultra in Treatment of Moderate to Severe Facial Wrinkles and Folds

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness and safety of Emervel Classic Lidocaine versus Juvederm® Ultra in the treatment of moderate to severe facial wrinkles and folds.

Official Title
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A Pivotal USA Randomized, Evaluator-blinded, Active-controlled, Multi-center, Split-face Comparison Study of Emervel Classic Lidocaine Versus Juvederm® Ultra in the Treatment of Moderate to Severe Facial Wrinkle Folds

Conditions
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Skin Wrinkling

Intervention / Treatment
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* Device: Emervel Classic Lidocaine
* Device: Juvederm® Ultra


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is a male or female 18 years of age or older The subject has bilateral nasolabial folds that, in the opinion of both the Blinded Evaluating Investigator and the Unblinded Injecting Investigator, can be corrected with an injectable dermal implant The subject has the same Wrinkle Severity Rating Scale (WSRS) score of 3 or 4 (moderate or severe) for each nasolabial fold Exclusion Criteria: The subject has active skin disease or inflammation on or near a nasolabial fold that, in the Principal Investigator's opinion, would interfere with the study device injections and/or study assessments. The subject has a history of sensitivity to hyaluronic acid The subject has a history of sensitivity to lidocaine or other amide type anesthetics The subject is, in the Principal Investigator's opinion, at undue risk based on the precautions, warnings and contraindications for local lidocaine anesthetics.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Emervel Classic Lidocaine<br>NLFs (Nasolabial Folds) were injected with Emervel Classic Lidocaine (20 mg/mL with 0.3% lidocaine). | Device: Emervel Classic Lidocaine<br>* 20 mg/mL + 0.3% lidocaine<br>|
| Active Comparator: Juvederm® Ultra<br>NLFs were injected with Juvéderm Ultra (24 mg/mL). | Device: Juvederm® Ultra<br>* 24mg/mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 24 After Final Initial Injection | WSRS is a validated 5-point reference scale with photographs that classifies facial wrinkles (nasolabial folds). WSRS represents clinically meaningful change in NLF severity from the adjacent grades where 1= absent (no visible fold; continuous skin line), 2 = mild (shallow but visible fold with a slight indentation; minor facial feature; implant expected to produce a slight improvement in appearance), 3 = excellent (correction is expected from injectable implant), 4 = severe (very long and deep folds; prominent facial feature; less than 2 mm visible fold when stretched; significant improvement expected from injectable implant), 5 = extreme (extremely deep and long folds, detrimental to facial appearance; 2 to 4 millimeter (mm) visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone). A negative change from baseline indicates improvement. | Baseline, Week 24 after final initial injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 3 After the Final Initial Injection | WSRS is a validated 5-point reference scale with photographs that classifies facial wrinkles (nasolabial folds). WSRS represents a clinically meaningful change in NLF severity from the adjacent grades where 1 = absent (no visible fold; continuous skin line), 2 = mild (shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance), 3 = excellent (correction is expected from injectable implant), 4 = severe (very long and deep folds; prominent facial feature; less than 2 mm visible fold when stretched; significant improvement is expected from injectable implant), 5 = extreme (extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone). A negative change from baseline indicates improvement. | Baseline, Week 3 after final initial injection | 
| Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 12 After Final Initial Injection | WSRS is a validated 5-point reference scale with photographs that classifies facial wrinkles (nasolabial folds). WSRS represents a clinically meaningful change in nasolabial fold severity from the adjacent grades where 1 = absent (no visible fold; continuous skin line), 2 = mild (shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance), 3 = excellent (correction is expected from injectable implant), 4 = severe (very long and deep folds; prominent facial feature; less than 2 mm visible fold when stretched; significant improvement is expected from injectable implant), 5 = extreme (extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone). A negative change from baseline indicates improvement. | Baseline, Week 12 after final initial injection | 
| Mean Change From Baseline in Wrinkle Severity Scale (WSRS) at Week 36 After Final Initial Injection | WSRS is a validated 5-point reference scale with photographs that classifies facial wrinkles (nasolabial folds). WSRS represents a clinically meaningful change in NLF severity from the adjacent grades where 1 = absent (no visible fold; continuous skin line), 2 = mild (shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance), 3 = excellent (correction is expected from injectable implant), 4 = severe (very long and deep folds; prominent facial feature; less than 2 mm visible fold when stretched; significant improvement is expected from injectable implant), 5 = extreme (extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone). A negative change from baseline indicates improvement. | Baseline, Week 36 after final initial injection | 
| Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 48 After Final Initial Injection | WSRS is a validated 5-point reference scale with photographs that classifies facial wrinkles (nasolabial folds). WSRS represents a clinically meaningful change in NLF severity from the adjacent grades where 1 = absent (no visible fold; continuous skin line), 2 = mild (shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance), 3 = excellent (correction is expected from injectable implant), 4 = severe (very long and deep folds; prominent facial feature; less than 2 mm visible fold when stretched; significant improvement is expected from injectable implant), 5 = extreme (extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone). A negative change from baseline indicates improvement. | Baseline, Week 48 after final initial injection | 
| Mean Change From Baseline in Participant Self-Assessment of Wrinkle Severity at Week 24 After Final Initial Injection | Participants self-assessment was measured by using a wrinkle severity scale with 1 being absent and 5 being extreme. Each participant was to perform an assessment of the wrinkle severity based on self-assessment score: 1= Absent (No visible fold; continuous skin line), 2= Mild (Shallow but visible fold with a slight indentation), 3= Moderate (Moderately deep folds), 4= Severe (Very long and deep fold), 5= Extreme (Extremely deep and long folds). A negative change from baseline indicates improvement. | Baseline, Week 24 after final initial injection | 
| Participant Pain Assessment After the Initial Injection | Participant pain severity for each NLF was assessed at time 0, 15, 30, 45, 60 minutes and 24 hours after the initial injection using an 11-point Numeric Pain Intensity Scale (NPIS).The NPIS was a pain screening tool, commonly used to assess pain severity at that moment in time using a 0-10 scale, with 0 is no pain and 10 is the worst possible pain. | At 0 ,15, 30, 45, 60 minutes and 24 hours after the initial injection | 
| Participant Pain Assessment After the Initial Touch-up Injection | Participant pain severity for each NLF was assessed at time 0, 15, 30, 45, 60 minutes and 24 hours after the initial injection using an 11-point Numeric Pain Intensity Scale (NPIS).The NPIS was a pain screening tool, commonly used to assess pain severity at that moment in time using a 0-10 scale, with 0 is no pain and 10 is the worst possible pain. | At 0, 15, 30, 45, 60 minutes and 24 hours after the Initial Touch-up Injection | 
| Number of Participants With Adverse Events (AEs) | AE was defined as any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the study drug. Number of participants with AEs were reported. Event was unrelated to study product or injection procedure. If the treated side where an AE occurred was not applicable, this AE was summarized under each treatment group. | From start of study drug administration up to 56 weeks |