A Study to Compare the Safety and Effectiveness of a Non-FDA Approved Device Dermal Gel Extra (DGE) and an FDA Approved Device for the Correction of Nasolabial Folds (NLFs)

Study Overview
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Brief Summary
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The purpose of this research study is to evaluate the safety and effectiveness of injection with DGE Injectable Gel (hyaluronic acid with lidocaine manufactured by Genzyme Biosurgery) as compared to injection with Restylane (a Food and Drug Administration (FDA) approved dermal filler) in patients undergoing cutaneous correction of the nasolabial folds (NLFs).

Detailed Description
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This study included an Initial and a Repeat Treatment period. The Initial Treatment period was a subject and evaluator-blinded, randomized split face study in which subjects received DGE in one nasolabial fold and Restylane in the other nasolabial fold. Both safety and efficacy were evaluated. In the Repeat Treatment Period, participants received DGE in both NLFs. Safety was evaluated.

Official Title
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A Subject- and Evaluator-Blinded, Randomized, Multi-Center Study to Evaluate the Safety and Effectiveness of Injection With DGE Injectable Gel as Compared to an FDA-Approved Dermal Filler in Subjects Undergoing Cutaneous Correction of Nasolabial Folds

Conditions
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Facial Wrinkles at the Nasolabial Folds

Intervention / Treatment
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* Device: Dermal Gel Extra (DGE)
* Device: Restylane
* Drug: EMLA Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (abbreviated list): Bilateral nasolabial folds (NLF) with severity score of 3 or 4 on the 6 point scale. Exclusion Criteria (abbreviated list): Pregnant/lactating women. Subjects who have an allergy to lidocaine, prilocaine or other amide-type anesthetic. Had a chemical peel at the NLF area within 4 weeks prior to study entry. In addition, subjects were restricted from undergoing chemical peels at the NLF area for the duration of the study. Had any treatment with Botox® injections in the upper 1/3 of the face within 2 weeks prior to entry into the study, or in the lower 2/3 of the face within 24 weeks prior to entry. In addition, subjects were restricted from receiving Botox injections in the face for the duration of the study. Received prior therapy to the face and/or neck (e.g., dermabrasion, face-lift, Thermage®,laser resurfacing, contour threads, non-ablative laser treatments) within 24 weeks prior to study entry. In addition, subjects were restricted from undergoing such therapy for the duration of the study. Had previous tissue augmentation at the NLF area within 24 weeks prior to study entry. In addition, subjects were restricted from undergoing tissue augmentation at the NLF area for the duration of the study. Had previous treatment at the NLF area with permanent implants (e.g., silicone,Softform®) or long-lasting fillers (e.g., RadiesseTM, Sculptra®, ArteFill® [Artecoll], or Bio-AlcamidTM). In addition, subjects were restricted from undergoing treatment with permanent implants or long-lasting fillers at the NLF area for the duration of the study. Had evidence of scar-related disease or delayed healing activity within one year prior to study enrollment. (Note: subjects with scars were eligible for study enrollment, although scars at the intended treatment sites were not treated.) Had a history of keloid formation. Had a history of hypo- or hyperpigmentation of the skin. Had any infection, unhealed wound, or active inflammatory process (e.g., skin eruptions such as cysts, pimples, rashes, or hives) at the injection site(s). Immunocompromised/immunosuppressed (e.g., HIV-positive, transplant recipient, or presently receiving chemotherapy).

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DGE<br>Participants received DGE in one nasolabial fold (NLF) of one side of their face (blinded, split-face study design) in the Initial Treatment period. Participants who continued into the Repeat Treatment period were treated with DGE as an open-label treatment. | Device: Dermal Gel Extra (DGE)<br>* Dermal Gel Extra (DGE) Injectable Gel contains hyaluronic acid with lidocaine. DGE was administered to nasolabial folds via the intradermal route. The Principal Investigator was instructed to inject a sufficient amount of DGE to ensure full correction of the NLF wrinkles (i.e., to the optimal level of correction achievable). Up to 2 touch-up treatments were allowed in the Initial Treatment period.<br>* Other names: hyaluronic acid and lidocaine;Drug: EMLA Cream<br>* EMLA Cream (Eutectic Mixture of Local Anesthetics) is an FDA-approved topical anesthetic comprised of 2.5% each of lidocaine/prilocaine. EMLA Cream was applied in approximately equal amounts prior to all injections of DGE and Restylane.<br>* Other names: prilocaine;|
| Active Comparator: Restylane<br>Participants received Restylane in one nasolabial fold (NLF) of one side of their face (blinded, split-face study design) in the Initial Treatment period. | Device: Restylane<br>* Restylane was administered to nasolabial folds via the intradermal route. The Principal Investigator was instructed to inject a sufficient amount of Restylane to ensure full correction of the NLF wrinkles (i.e., to the optimal level of correction achievable). Up to 2 touch-up treatments were allowed in the Initial Treatment period.<br>* Other names: hyaluronic acid;Drug: EMLA Cream<br>* EMLA Cream (Eutectic Mixture of Local Anesthetics) is an FDA-approved topical anesthetic comprised of 2.5% each of lidocaine/prilocaine. EMLA Cream was applied in approximately equal amounts prior to all injections of DGE and Restylane.<br>* Other names: prilocaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Blinded Evaluator's Assessment of Nasolabial Fold (NLF) Wrinkle Severity at Week 24 | This was a comparison of the mean change between Baseline and the Week 24 score (baseline minus week 24 scores) in the blinded evaluators' assessments of NLF wrinkle severity. A positive value for the mean change indicates an improvement. Genzyme 6-Point Grading Scale (GGS) for NLF was used for the assessment. A GGS score of zero indicates no wrinkles and a score of 5 indicates very deep wrinkles with redundant folds. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant's Pain Assessment During the Initial Treatment Measured on a Visual Analog Scale (VAS) | The pain experienced by each participant at the time of injection (time 0) and at 15 and 30 minutes after injection during the initial treatment visit was evaluated. Pain was measured using a VAS of 0 mm (no pain) to 100 mm (extreme pain). | Day 1 | 
| Change From Baseline in the Blinded Evaluator's Assessment of Nasolabial Folds (NLF) Wrinkle Severity at Week 36 | Mean change between Baseline and the Week 36 score (Baseline minus week 36 scores) in the blinded evaluators' assessments of NLF wrinkle severity. A positive value for the mean change indicates an improvement. Genzyme 6-Point Grading Scale (GGS) for NLF was used for the assessment. A GGS score of zero indicates no wrinkles and a score of 5 indicates very deep wrinkles with redundant folds. | Week 36 | 
| Number of Participants With at Least a 1 Point Improvement From Baseline in the Blinded Evaluator's Assessment of Wrinkle Severity at Week 24 | Count of participants with at least a 1-point improvement from Baseline in the Genzyme 6-Point Grading Scale (GGS) at Week 24. A GGS score of zero indicates no wrinkles and a score of 5 indicates very deep wrinkles with redundant folds. | Week 24 | 
| Participant Product Preference at Week 24 | Participants indicated their product preference at Week 24 after Date of Optimal Correction (DOC). | Week 24 | 
| Participant Product Preference at Week 36 | Participants indicated their product preference at Week 36 after Date of Optimal Correction (DOC). | Week 36 | 
| Number of Participants With Treatment-Emergent Adverse Events During the Initial Treatment Period | Counts of participants with treatment-emergent adverse events (AEs) from the time of injection up to Week 36. AEs are presented regardless of relationship to study device and/or procedure. If a participant had more than one occurrence of the same AE, he/she was counted only once. The most severe occurrence of an AE, as well as the most extreme relationship of the AE to the device, was indicated in cases of multiple occurrences of the same AE. For AEs by relationship, procedure-related and device-related AEs are not mutually exclusive and therefore are not additive. | Weeks 1-36 | 
| Number of Participants With Treatment-Emergent Adverse Events During the Repeat Treatment Period | Count of participants with treatment-emergent adverse events (AEs) from the time of injection for the repeat treatment period up to week 47. AEs are presented regardless of relationship to study device and/or procedure. If a participant had more than one occurrence of the same AE, he/she was counted only once. The most severe occurrence of an AE, as well as most extreme relationship of the AE to the device, was indicated in cases of multiple occurrences of the same AE. For AEs by relationship, procedure-related and device-related AEs are not mutually exclusive and therefore are not additive. | weeks 36 up to 47 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nasolabial folds, facial wrinkles