RHA® 4 With New Anesthetic - Nasolabial Folds

• Sponsor: Teoxane SA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04087395
• Collaborator: (none)
• Enrollment: 30
• Locations: 3
• Arms: 2
• Actual Duration (Months): 12.4
• Patients Per Site: 10
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This is a randomized, controlled, double-blinded, within-subject (split-face), multicenter, prospective study to investigate whether RHA® 4 with New Anesthetic Agent is non-inferior to RHA® 4 (with lidocaine) in terms of injection site pain felt by the subject during injection.

At screening, the Treating Investigator (TI) evaluated subjects' NLF severity (using the Wrinkle Severity Rating Scale; WSRS) to confirm eligibility and to establish a pre-treatment score for assessing aesthetic improvement.

At Visit 1, RHA® 4 With New Anesthetic Agent was administered in a random sequence (first or second injection) and side of the face (left or right) and RHA® 4 with lidocaine was administered to the other side. Study subjects and the TI injecting study devices were blinded.

Immediately after injection of each side, subjects rated injection site pain experienced during injection using a 100 mm Visual Analog Scale (VAS). Injection site pain in each side of the face was also assessed at 15, 30, 45 and 60 minutes post-injection.

Safety evaluation consisted of AE assessments, a 30-day CTR (Common Treatment Response) diary and a follow-up call performed by the study site at 72 hours after injection.

Subjects attended Visit 2 (30 days post-injection) where efficacy and safety assessments will be conducted. Subjects who present with an unresolved clinically significant device related AE at Visit 2 received the optional follow-up phone call no later than 30 days after Visit 2. If the clinically significant AE remained unresolved, the Investigator requested that the subject attended the optional in-clinic follow-up visit (i.e., Visit 3) within 5 working days. Follow-up of the clinically significant AE continued until the AE was resolved or the TI determines that additional follow-up was not necessary.

Condition or Disease	Intervention/Treatment	Phase
Aging; Pain	Device: RHA®4 with new anesthetic agent; Device: RHA®4-Lidocaine	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Split-face designSplit-face design
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Controlled, Double-blinded, Within-subject (Split-face), Multicenter, Prospective Clinical Study to Compare the Level of Pain Using the Dermal Filler RHA® 4 Formulated With Two Different Anesthetics in the Treatment of Nasolabial Folds
• Actual Study Start Date: Oct 30, 2019
• Actual Primary Completion Date: Feb 18, 2020
• Actual Study Completion Date: Nov 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RHA®4 with new anesthetic agent Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side.	Device: RHA®4 with new anesthetic agent; A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w of new anesthetic agent in a physiologic buffer.
Experimental: RHA®4-Lidocaine Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side.	Device: RHA®4-Lidocaine; A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w lidocaine in a physiologic buffer.

Outcome Measures

Primary Outcome Measures

1. Non-inferiority of RHA® 4 With New Anesthetic Agent Versus RHA® 4-Lidocaine in Terms of Reducing Pain During Device Injection Into Nasolabial Folds. [Visit 1 - During Injection]

   Injection pain during injection will be based on the 100 mm Visual Analog Scale (VAS), as assessed by subjects immediately after injection of each nasolabial fold. VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain.

Secondary Outcome Measures

1. Difference Between RHA® 4 With New Anesthetic Agent Versus RHA® 4-Lidocaine in Term of Reducing Pain at 15, 30, 45 and 60 Minutes Post-injection in Nasolabial Folds of Each Side of the Face. [Visit 1 - 15, 30, 45 and 60 minutes post-injection]

   Injection pain was measured on the 100 mm Visual Analog Scale (VAS), as assessed by subjects in nasolabial fold of each side of the face. VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain

2. Change in NLF WSRS Score Between Baseline and Day 30 as Assessed by the Treating Investigator [Visit 1 - Baseline (pre-injection), Visit 1 (post-injection), Visit 2 (Day 30)]

   NLF-WSRS (Nasolabial Folds- Wrinkle Severity Rating Scale) is a validated 5-grade scale with 1 being "Absent" and 5 being "Extreme"

3. Percentage of Responders Based on the Intra-individual Improvement of at Least One Grade on the Nasolabial Folds Wrinkle Severity Rating Scale (NLF-WSRS) Compared to Baseline, as Assessed by the TI [Visit 1 (Baseline, pre-injection), Visit 1 (post-injection), Visit 2 (Day 30)]

   A responder corresponds to a subject with an intra-individual improvement of at least one grade on the NLF WSRS compared to Baseline, as assessed by the TI

4. Subject's Perception of Treatment Effectiveness as Per the FACE-Q (Nasolabial Folds Domain) Questionnaire. The FACE-Q Measures the Experience and Outcomes of Aesthetic Facial Procedures From the Patient's Perspective. [Visit 1 (Baseline) and Visit 2 (Day 30)]

   FACE-Q questionnaire is composed of 5 questions with a score linked to answers (1 being 'Not at all' and 4 being 'Extremely'). The subject will be instructed as follows: "These questions ask about how you look right now. For each question, circle only one answer. With your nasolabial folds in mind (the deep lines that run downward from the sides of your nose), in the past week, how much have you been bothered by:", and will provide response. To calculate the FACE-Q, outcomes from all 5 questions were pooled, data were transformed so that higher scores reflected a superior outcome, and adapted to a scale of 100 units (i.e. lowest score = 0, highest score = 100).

5. Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) by the Treating Investigator (TI) [Visit 1 (just after receiving treatment) and Visit 2 (Day 30)]

   Global Aesthetic Improvement (GAI) is a subjective 5-grade scale comprised of "much improved, improved, no change, worse, and much worse". GAI was assessed using the baseline photograph. Each side of the face will be assessed independently.

6. Number of Global Aesthetic Improvement (GAI) Responders (i.e., Scoring Either "Much Improved" or "Improved") on GAI Scale According to Subject's Self-assessment [Visit 1 (just after receiving treatment) and Visit 2 (Day 30)]

   Global Aesthetic Improvement (GAI) is a subjective 5-grade scale comprised of "much improved, improved, no change, worse, and much worse". GAI was assessed using the baseline photograph. Subjects were instructed: "Use a mirror to compare your face to the photograph provided to you and rate the degree of aesthetic improvement by using the following scale". Each side of the face was assessed independently.

7. Number of Subjects "Satisfied" or "Very Satisfied" With Study Treatment Using the Subject's Satisfaction Scale [Visit 1 (just after receiving treatment) and Visit 2 (Day 30)]

   The Subject Satisfaction Scale is a subjective, balanced, 5-point scale assessing subject satisfaction with study treatment. Possible scores range from with 1 (very satisfied) to 5 (very dissatisfied). Proportion of subjects who were Satisfied (i.e., 1-Very Satisfied + 2-Satisfied) was compared to the proportion of subjects who were Not Satisfied (i.e., 3-Neither Satisfied nor dissatisfied + 4-Dissatisfied + 5-Very Dissatisfied)

8. Number of Subjects With Post Injection Treatment Responses (From Common Treatment Responses (CTR) Diary) for Safety Evaluation of RHA® 4 With New Anesthetic Agent Versus RHA® 4-Lidocaine [During 30 days after injection]

   The subjects received a diary booklet and instructions for recording their observations of the Common Treatment Responses to the study treatments during 30 days following the injection. The diary were discussed during follow-up phone call and visit. Subjects were instructed to complete the diary at approximately the same time each day (i.e., am or pm). The subject diary captured the following Common Treatment Responses (CTR) that occur following the injection of a dermal filler; specifically, redness, pain, tenderness, firmness, swelling, lumps/bumps, bruising, itching, discoloration, and "other". The 30-day patient CTR diary included a detailed glossary describing all signs/symptoms listed in the diary; an option was provided to rate "other" if the subject experienced a sign/symptom that is not listed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Outpatient, male or female of any race, 22 years of age or older. Female subjects of childbearing potential must have a negative UPT at Visit 1 and practice a reliable method of contraception throughout the study.

2. Moderate to severe bilateral nasolabial folds (grade 3 or 4 on the five-point WSRS).

3. Nasolabial folds of the same WSRS grade on the left and right sides of the face.

4. Able to follow study instructions and complete all required visits.

5. Sign the IRB-approved ICF, Photographic Release Form, the Authorization for Use and release of Health and Research Study Information (HIPAA) form, and if applicable the California Experimental Research Subject's Bill of Rights prior to any study-related procedures being performed.

Exclusion Criteria:

1. Female subjects who are pregnant, breast-feeding, or of childbearing potential and not practicing reliable birth control.

2. Known hypersensitivity or previous allergic reaction to any component of the study devices.

3. Use of a prohibited treatment/procedure within time periods defined in the protocol

4. Known sensitivity to local anesthetics of the amide type, history of multiple severe allergies, or history of anaphylactic shock.

5. History of active chronic debilitating systemic disease that, in the opinion of the investigator, would make the subject a poor candidate in the study.

6. History of connective tissue disease.

7. Malignancy (excluding non-melanoma skin cancer) within the past 5 years.

8. History of skin cancer in the treatment area.

9. Clinically active disease or infection in the NLF area.

10. Medical or psychiatric conditions that may increase the risk associated with study participation or may interfere with the interpretation of study results or compliance of the subject and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.

11. Clinically significant alcohol or drug abuse, or history of poor cooperation or unreliability.

12. Exposure to any other investigational drug/device within 90 days of entering the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California	Beverly Hills	California	United States	90210
2	Florida	Coral Gables	Florida	United States	33146
3	Illinois	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Teoxane SA

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Sep 10, 2019
• Statistical Analysis Plan - Feb 19, 2020

More Information

Publications

None provided.

• Responsible Party: Teoxane SA
• ClinicalTrials.gov Identifier: NCT04087395
• Other Study ID Numbers: TEO-RHA-1802
• First Posted: Sep 12, 2019
• Last Update Posted: Jan 24, 2022
• Last Verified: May 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Teoxane SA: Hyaluronic Acid; Anesthetic; Lidocaine; Nasolabial Folds
• Additional relevant MeSH terms: Lidocaine; Anesthetics

Study Results

Participant Flow

Arm/Group Title	Split-face Study : Bilateral Treatment RHA® 4 With New Anesthetic Agent Vs RHA® 4-Lidocaine
Arm/Group Description	Split-face injection of RHA® 4 with new anesthetic agent in the NLF on one side of the face and RHA® 4- Lidocaine in the NLF on the opposite side of the face. RHA® 4 with new anesthetic agent was administered in a random sequence (first or second injection) on one side and RHA®4-Lidocaine was administered in the side.
Period Title: Overall Study
STARTED	30
COMPLETED	30
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Split-face Study : Bilateral Treatment With RHA®4 With New Anesthetic Agent Vs RHA®4-Lidocaine
Arm/Group Description	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial folds on one side of the face and RHA®4-Lidocaine in the perioral rhytids on the opposite side of the face
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.0 (9.7)
Sex: Female, Male (Count of Participants)
Female	27 90%
Male	3 10%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 40%
Not Hispanic or Latino	18 60%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 10%
White	27 90%
More than one race	0 0%
Unknown or Not Reported	0 0%
Fitzpatrick Skin Type (Count of Participants)
Types I to III (as assessed by TI at screening)	19 63.3%
Types IV to VI (as assessed by TI at screening)	11 36.7%

Outcome Measures

1. Primary Outcome

Title	Non-inferiority of RHA® 4 With New Anesthetic Agent Versus RHA® 4-Lidocaine in Terms of Reducing Pain During Device Injection Into Nasolabial Folds.
Description	Injection pain during injection will be based on the 100 mm Visual Analog Scale (VAS), as assessed by subjects immediately after injection of each nasolabial fold. VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain.
Time Frame	Visit 1 - During Injection

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RHA®4 With New Anesthetic Agent	RHA®4-Lidocaine
Arm/Group Description	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face.	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face.
Measure Participants	30	30
Mean (Standard Deviation) [mm]	17.1 (18.38)	16.3 (18.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RHA®4 With New Anesthetic Agent, RHA®4-Lidocaine
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	To achieve non-inferiority, the observed p-value must be <= 0.5 taking into account of the non-inferiority margin (i.e., 10mm difference in Pain VAS between the two treatment groups).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	One-sided paired student t-test
	Method	t-test, 1 sided
	Comments

2. Secondary Outcome

Title	Difference Between RHA® 4 With New Anesthetic Agent Versus RHA® 4-Lidocaine in Term of Reducing Pain at 15, 30, 45 and 60 Minutes Post-injection in Nasolabial Folds of Each Side of the Face.
Description	Injection pain was measured on the 100 mm Visual Analog Scale (VAS), as assessed by subjects in nasolabial fold of each side of the face. VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain
Time Frame	Visit 1 - 15, 30, 45 and 60 minutes post-injection

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RHA®4 With New Anesthetic Agent	RHA®4-Lidocaine
Arm/Group Description	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4 with new anesthetic agent: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w of new anesthetic agent in a physiologic buffer.	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4-Lidocaine: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w lidocaine in a physiologic buffer.
Measure Participants	30	30
15 Min	4.9 (12.33)	5.1 (15.94)
30 Min	2.0 (5.66)	3.1 (12.30)
45 Min	0.0 (0.00)	2.1 (11.68)
60 Min	0.0 (0.00)	1.9 (10.22)

3. Secondary Outcome

Title	Change in NLF WSRS Score Between Baseline and Day 30 as Assessed by the Treating Investigator
Description	NLF-WSRS (Nasolabial Folds- Wrinkle Severity Rating Scale) is a validated 5-grade scale with 1 being "Absent" and 5 being "Extreme"
Time Frame	Visit 1 - Baseline (pre-injection), Visit 1 (post-injection), Visit 2 (Day 30)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RHA®4 With New Anesthetic Agent	RHA®4-Lidocaine
Arm/Group Description	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4 with new anesthetic agent: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w of new anesthetic agent in a physiologic buffer.	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4-Lidocaine: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w lidocaine in a physiologic buffer.
Measure Participants	30	30
Visit 1 (post-injection)	-1.8 (0.57)	-1.8 (0.57)
Visit 2 (Day 30)	-1.9 (0.48)	-1.8 (0.63)

4. Secondary Outcome

Title	Percentage of Responders Based on the Intra-individual Improvement of at Least One Grade on the Nasolabial Folds Wrinkle Severity Rating Scale (NLF-WSRS) Compared to Baseline, as Assessed by the TI
Description	A responder corresponds to a subject with an intra-individual improvement of at least one grade on the NLF WSRS compared to Baseline, as assessed by the TI
Time Frame	Visit 1 (Baseline, pre-injection), Visit 1 (post-injection), Visit 2 (Day 30)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RHA®4 With New Anesthetic Agent	RHA®4-Lidocaine
Arm/Group Description	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4 with new anesthetic agent: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w of new anesthetic agent in a physiologic buffer.	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4-Lidocaine: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w lidocaine in a physiologic buffer.
Measure Participants	30	30
Responder	30 100%	30 NaN
Not Responder	0 0%	0 NaN
Responder	30 100%	29 NaN
Not Responder	0 0%	1 NaN

5. Secondary Outcome

Title	Subject's Perception of Treatment Effectiveness as Per the FACE-Q (Nasolabial Folds Domain) Questionnaire. The FACE-Q Measures the Experience and Outcomes of Aesthetic Facial Procedures From the Patient's Perspective.
Description	FACE-Q questionnaire is composed of 5 questions with a score linked to answers (1 being 'Not at all' and 4 being 'Extremely'). The subject will be instructed as follows: "These questions ask about how you look right now. For each question, circle only one answer. With your nasolabial folds in mind (the deep lines that run downward from the sides of your nose), in the past week, how much have you been bothered by:", and will provide response. To calculate the FACE-Q, outcomes from all 5 questions were pooled, data were transformed so that higher scores reflected a superior outcome, and adapted to a scale of 100 units (i.e. lowest score = 0, highest score = 100).
Time Frame	Visit 1 (Baseline) and Visit 2 (Day 30)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RHA®4 With New Anesthetic Agent	RHA®4-Lidocaine
Arm/Group Description	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4 with new anesthetic agent: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w of new anesthetic agent in a physiologic buffer.	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4-Lidocaine: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w lidocaine in a physiologic buffer.
Measure Participants	30	30
Baseline Face-Q Score	25.2 (21.12)	24.3 (20.34)
Day 30 Face-Q Score	89.0 (15.19)	88.5 (16.16)
Face-Q Change from Baseline to Day 30	63.8 (24.69)	64.2 (25.06)

6. Secondary Outcome

Title	Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) by the Treating Investigator (TI)
Description	Global Aesthetic Improvement (GAI) is a subjective 5-grade scale comprised of "much improved, improved, no change, worse, and much worse". GAI was assessed using the baseline photograph. Each side of the face will be assessed independently.
Time Frame	Visit 1 (just after receiving treatment) and Visit 2 (Day 30)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RHA®4 With New Anesthetic Agent	RHA®4-Lidocaine
Arm/Group Description	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4 with new anesthetic agent: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w of new anesthetic agent in a physiologic buffer.	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4-Lidocaine: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w lidocaine in a physiologic buffer.
Measure Participants	30	30
Visit 1 (post-injection)	30 100%	30 NaN
Visit 2 (Day 30)	30 100%	29 NaN

7. Secondary Outcome

Title	Number of Global Aesthetic Improvement (GAI) Responders (i.e., Scoring Either "Much Improved" or "Improved") on GAI Scale According to Subject's Self-assessment
Description	Global Aesthetic Improvement (GAI) is a subjective 5-grade scale comprised of "much improved, improved, no change, worse, and much worse". GAI was assessed using the baseline photograph. Subjects were instructed: "Use a mirror to compare your face to the photograph provided to you and rate the degree of aesthetic improvement by using the following scale". Each side of the face was assessed independently.
Time Frame	Visit 1 (just after receiving treatment) and Visit 2 (Day 30)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RHA®4 With New Anesthetic Agent	RHA®4-Lidocaine
Arm/Group Description	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4 with new anesthetic agent: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w of new anesthetic agent in a physiologic buffer.	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4-Lidocaine: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w lidocaine in a physiologic buffer.
Measure Participants	30	30
Visit 1 (post-injection)	30 100%	30 NaN
Visit 2 (Day 30)	30 100%	30 NaN

8. Secondary Outcome

Title	Number of Subjects "Satisfied" or "Very Satisfied" With Study Treatment Using the Subject's Satisfaction Scale
Description	The Subject Satisfaction Scale is a subjective, balanced, 5-point scale assessing subject satisfaction with study treatment. Possible scores range from with 1 (very satisfied) to 5 (very dissatisfied). Proportion of subjects who were Satisfied (i.e., 1-Very Satisfied + 2-Satisfied) was compared to the proportion of subjects who were Not Satisfied (i.e., 3-Neither Satisfied nor dissatisfied + 4-Dissatisfied + 5-Very Dissatisfied)
Time Frame	Visit 1 (just after receiving treatment) and Visit 2 (Day 30)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RHA®4 With New Anesthetic Agent	RHA®4-Lidocaine
Arm/Group Description	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4 with new anesthetic agent: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w of new anesthetic agent in a physiologic buffer.	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4-Lidocaine: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w lidocaine in a physiologic buffer.
Measure Participants	30	30
Visit 1 (post-injection) : Satisfied	30 100%	30 NaN
Visit 1 (post-inj): Not Satisfied	0 0%	0 NaN
Visit 2 (Day 30) : Satisfied (i.e., 1-Very Satisfied + 2-Satisfied)	29 96.7%	29 NaN
Visit 2 (Day 30) : Not Satisfied	1 3.3%	1 NaN

9. Secondary Outcome

Title	Number of Subjects With Post Injection Treatment Responses (From Common Treatment Responses (CTR) Diary) for Safety Evaluation of RHA® 4 With New Anesthetic Agent Versus RHA® 4-Lidocaine
Description	The subjects received a diary booklet and instructions for recording their observations of the Common Treatment Responses to the study treatments during 30 days following the injection. The diary were discussed during follow-up phone call and visit. Subjects were instructed to complete the diary at approximately the same time each day (i.e., am or pm). The subject diary captured the following Common Treatment Responses (CTR) that occur following the injection of a dermal filler; specifically, redness, pain, tenderness, firmness, swelling, lumps/bumps, bruising, itching, discoloration, and "other". The 30-day patient CTR diary included a detailed glossary describing all signs/symptoms listed in the diary; an option was provided to rate "other" if the subject experienced a sign/symptom that is not listed.
Time Frame	During 30 days after injection

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RHA®4 With New Anesthetic Agent	RHA®4-Lidocaine
Arm/Group Description	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4 with new anesthetic agent: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w of new anesthetic agent in a physiologic buffer.	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. RHA®4-Lidocaine: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 23 mg/g and 0.3% w/w lidocaine in a physiologic buffer.
Measure Participants	30	30
Bruising	19 63.3%	21 NaN
Discoloration	11 36.7%	12 NaN
Firmness	24 80%	22 NaN
Itching	7 23.3%	6 NaN
Lumps/Bumps	22 73.3%	21 NaN
Pain	12 40%	9 NaN
Redness	21 70%	20 NaN
Swelling	21 70%	23 NaN
Tenderness	24 80%	24 NaN
Paresthesia	1 3.3%	0 NaN

Adverse Events

Time Frame	approximatly 1 month (35 days, overall study duration)
Arm/Group Title	RHA®4 With New Anesthetic Agent		RHA®4-Lidocaine
Arm/Group Description	Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face.		Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face.
All Cause Mortality
	RHA®4 With New Anesthetic Agent		RHA®4-Lidocaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Serious Adverse Events
	RHA®4 With New Anesthetic Agent		RHA®4-Lidocaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	RHA®4 With New Anesthetic Agent		RHA®4-Lidocaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/30 (16.7%)		4/30 (13.3%)
General disorders
Injection site induration	3/30 (10%)	3	4/30 (13.3%)	4
Injection site mass	1/30 (3.3%)	1	0/30 (0%)	0
Injection site pruritus	1/30 (3.3%)	1	1/30 (3.3%)	1
Nervous system disorders
Paresthesia oral	1/30 (3.3%)	1	0/30 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.