TEOSYAL® RHA Ultra Deep and Perlane-L® for the Correction of Nasolabial Folds

• Sponsor: Teoxane SA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02253147
• Collaborator: ethica Clinical Research Inc. (Industry)
• Enrollment: 140
• Locations: 4
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 35
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effectiveness and safety of TEOSYAL® RHA Ultra Deep versus Perlane-L® in the treatment of moderate to severe nasolabial folds. This is a controlled, randomized, double-blinded, within subject (split-face), multicenter, prospective clinical study.

Condition or Disease	Intervention/Treatment	Phase
Nasolabial Folds, Wrinkles	Device: TEOSYAL® RHA Ultra Deep	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Controlled, Randomized, Double-Blinded, Within-Subject, Multicenter, Prospective Clinical Study of TEOSYAL® RHA (Resilient Hyaluronic Acid) Ultra Deep Versus Perlane-L® in the Treatment of Moderate to Severe Nasolabial Folds
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Left side TEOSYAL® RHA Ultra Deep, Right side Perlane-L® Split-face injection of TEOSYAL® RHA Ultra Deep into the left Naso Labial Folds (NLFs) and Perlane-L® into the right NLF (n=120). Up to 3.0 mL injected per NLF. Touch-up treatment provided at 2 weeks (up to 3.0 mL per NLF).	Device: TEOSYAL® RHA Ultra Deep; A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus equi bacteria, formulated to a concentration of 23 mg/mL and 0.3% w/w lidocaine in a physiologic buffer. It is supplied in individual treatment syringes with 27Gauge ½" disposable sterile needles.
Experimental: Left side Perlane-L®, Right side TEOSYAL® RHA Ultra Deep Split-face injection of Perlane-L® into the left Naso Labial Folds (NLFs) and TEOSYAL® RHA Ultra Deep into the right NLF (n=120). Up to 3.0 mL injected per NLF. Touch-up treatment provided at 2 weeks (up to 3.0 mL per NLF).	Device: TEOSYAL® RHA Ultra Deep; A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus equi bacteria, formulated to a concentration of 23 mg/mL and 0.3% w/w lidocaine in a physiologic buffer. It is supplied in individual treatment syringes with 27Gauge ½" disposable sterile needles.

Outcome Measures

Primary Outcome Measures

1. Non-inferiority of the Delta of the WSRS Score Between W24 and Baseline for TEOSYAL® RHA Ultra Deep Versus Perlane-L® for the Correction of Moderate to Severe Naso-Labial Folds Based on the Wrinkle Severity Rating Scale (WSRS) Score Assessed by the BLE. [Baseline and 24 weeks after last treatment]

   WSRS (Wrinkle Severity Rating Scale) is a validated 5-point scale with 1 being 'absent' and 5 being 'extreme'. BLE =Blinded Live Evaluator

Secondary Outcome Measures

1. Post Injection Treatment Responses (From Common Treatment Responses (CTR) Diary) for Safety Evaluation of TEOSYAL® RHA Ultra Deep Versus Perlane-L® [During 14 days after initial treatment (D0) and touch-up (2 weeks)]

   The subjects received a diary booklet and instructions for recording his/her observations of the Common Treatment Responses of the study treatments for the first 14 days after each treatment (initial, touch-up). The diary was discussed during each telephone follow-up visit. Subjects should 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 14-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. The table presents the number of subjects experiencing at least 1 Common Treatment Response (CTR)

2. Assessment of Injection Site Pain (Visual Analog Scale) of TEOSYAL® RHA Ultra Deep Versus Perlane-L® [During Injection and 5, 15, 30 minutes post-injection]

   VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain

3. Delta of the WSRS Score Between W24,36,52 and 64 and Baseline for TEOSYAL® RHA Ultra Deep Versus Perlane-L® for the Correction of Moderate to Severe NLFs Based on the Wrinkle Severity Rating Scale (WSRS) Score Assessed by the Blinded Live Evaluator (BLE) [Baseline and Weeks 24, 36, 52, 64]

   WSRS (Wrinkle Severity Rating Scale) is a validated 5-point scale with 1 being 'absent' and 5 being 'extreme'.

4. Delta of the WSRS Score Between W2,4,12,24,36,52,64 and Baseline for TEOSYAL® RHA Ultra Deep Versus Perlane-L® for the Correction of Moderate to Severe NLFs Based on the Wrinkle Severity Rating Scale (WSRS) Score Assessed by the Treating Investigator (TI) [Baseline and Weeks 2, 4, 12, 24, 36, 52, 64]

   WSRS (Wrinkle Severity Rating Scale) is a validated 5-point scale with 1 being 'absent' and 5 being 'extreme'.

5. Percentage of Responders Based on the Intra-individual Improvement of at Least One Grade in the Wrinkle Severity Rating Scale (WSRS) Compared to Baseline Assessed by the BLE [Baseline and Weeks 24, 36, 52, 64]

   A responder correspond to a subject with an intra-individual improvement of at least one grade in the WSRS compared to Baseline

6. Percentage of Responders Based on the Intra-individual Improvement of at Least One Grade in the Wrinkle Severity Rating Scale (WSRS) Compared to Baseline Assessed by the TI [Baseline and Weeks 2, 4, 12, 24, 36, 52, 64]

   A responder correspond to a subject with an intra-individual improvement of at least one grade in the WSRS compared to baseline

7. Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) by the Blinded Live Evaluator (BLE) [Weeks 24, 36, 52, 64]

   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 was assessed independently.

8. Number of Global Aesthetic Improvement (GAI) Responders (i.e., Scoring Either "Much Improved" or "Improved") on GAI Scale. [Weeks 4, 12, 24, 36, 52, 64]

   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 will be 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.

9. Subject's Perception of Treatment Effectiveness as Per the FACE-Q (NLF Domain) Questionnaire [Immediately post-injection, and weeks 2, 4, 12, 24, 36, 52, 64]

   The FACE-Q measures the experience and outcomes of aesthetic facial procedures from the patient's perspective. 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 was instructed as follows: "These questions ask about how you look right now. 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 provided response. How deep your nasolabial fold are? How your nasolabial folds look when your face is relaxed (still)? How old your nasolabial folds make you look? How your nasolabial folds look when you smile? How your nasolabial folds look compared with other people your age? To calculate the FACE-Q, outcomes from all 5 questions were pooled and adapted to a scale to 100 units. Data were also transformed so that higher scores reflected a beneficial outcome.

10. Subject's Satisfaction Score [Weeks 2, 4, 12, 24, 36, 52, 64]

    Subjective 5-point scale with 1 being 'very satisfied' and 5 being 'very dissatisfied'

11. Volume to Obtain Optimal Cosmetic Result (Initial Treatment + Touch-up) [Week 2]

12. Number of Subjects Receiving Touch-up Treatment [Week 2]

13. Number of Subjects Receiving Re-treatment [Weeks 24, 36, 52, 64]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Outpatient, male or female of any race, 22 years of age or older; female subjects of childbearing potential must have a negative Urine Pregnancy Test and practice a reliable method of contraception;

• NLFs classified as WSRS grade 3 or 4 (same score for each side);

• Willing to abstain from facial aesthetic procedures/therapies that could interfere with study evaluations;

• Able to follow study instructions and likely to complete all required visits;

• Signed informed consent and HIPAA form.

Exclusion Criteria:

• Female subjects that are pregnant, breast-feeding or of childbearing potential and not practicing reliable birth control;

• Known hypersensitivity/allergy to any component of the study devices;

• Known sensitivity to local anesthetics of the amide type, history of multiple severe allergies, history of anaphylactic shock;

• Known susceptibility to keloid formation, hypertrophic scarring or clinically significant skin pigmentation disorders;

• Clinically significant active skin disease within 6 months;

• History of active chronic debilitating systemic disease;

• History of connective tissue disease;

• History of malignancy (excl. non-melanoma skin cancer) within past 5 years;

• History of bleeding disorders;

• Need for clinically significant and continuous medical treatment within 2 weeks prior to first visit;

• Received/used a prohibited treatment/procedure within certain time periods (e.g., bioresorbable fillers, NSAIDS, ASA, high dose vitamin E, corticosteroids, interferon, anti-coagulation therapies, laser/light therapies, botulinum toxin injections (frontalis and glabella complex treatment permitted), prescription strength topical retinoids, facial peels, excisional facial surgery, clinically significant oral or maxillofacial surgery).

• Evidence of clinically significant alcohol or drug abuse, or history of poor cooperation, non-compliance with medical treatment, or unreliability

• Exhibit a physical attribute(s) that may prevent assessment or treatment of NLFs such as excessive facial hair, traumatic or surgical facial scars, and/or excessive hyperpigmentation in the treatment areas.

• A condition or situation that may put the subject at significant risk, confound the study results, or significantly interfere with the subject participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	United States	Beverly Hills	California	United States
2	United States	Bradenton	Florida	United States
3	United States	Chapel Hill	North Carolina	United States
4	United States	Philadelphia	Pennsylvania	United States

Sponsors and Collaborators

• Teoxane SA
• ethica Clinical Research Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teoxane SA
• ClinicalTrials.gov Identifier: NCT02253147
• Other Study ID Numbers: TEO-RHA-1402
• First Posted: Oct 1, 2014
• Last Update Posted: Mar 27, 2018
• Last Verified: Feb 1, 2018

• Keywords provided by Teoxane SA: Nasolabial folds; Dermal filler; Hyaluronic acid (HA); Wrinkles

Study Results

Participant Flow

Recruitment Details	A total of 120 were randomized for a split-face injection of RHA Ultra Deep and Perlane-L. 20 subjects were randomized to an untreated group (recruited only to avoid Blinded Live Evaluator to be biased so, not presented)
Pre-assignment Detail	2 subjects randomized to the RHA UD/Perlane discontinued participation prior to receiving study treatment (N=118) 2 subjects randomized to the untreated group received injections with RHA UD/Perlane. These subjects were placed in the SAFT population for safety evaluations (SAFT population n=120)

Arm/Group Title	TEOSYAL® RHA Ultra Deep / Perlane-L®
Arm/Group Description	Split-face injection of TEOSYAL® RHA Ultra Deep into one NLF and Perlane-L® into the contralateral NLF. Up to 3.0 mL injected per NLF (deep-dermis to superficial subcutaneous). Touch-up treatment provided at 2 weeks (up to 3.0 mL per NLF). TEOSYAL® RHA Ultra Deep: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus equi bacteria, formulated to a concentration of 23 mg/mL and 0.3% w/w lidocaine in a physiologic buffer. It is supplied in individual treatment syringes with 27G½" disposable sterile needles.
Period Title: Overall Study
STARTED	118
N Patients at W24 (Primary Outcome)	88
N Patients at W36	86
N Patients at W52	84
COMPLETED	71
NOT COMPLETED	47

Baseline Characteristics

Arm/Group Title	TEOSYAL® RHA Ultra Deep / Perlane-L®
Arm/Group Description	Split-face injection of TEOSYAL® RHA Ultra Deep into one NLF and Perlane-L® into the contralateral NLF. Up to 3.0 mL injected per NLF (deep-dermis to superficial subcutaneous). Touch-up treatment provided at 2 weeks (up to 3.0 mL per NLF). TEOSYAL® RHA Ultra Deep: A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus equi bacteria, formulated to a concentration of 23 mg/mL and 0.3% w/w lidocaine in a physiologic buffer. It is supplied in individual treatment syringes with 27G½" disposable sterile needles.
Overall Participants	118
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.4 (10.0)
Sex: Female, Male (Count of Participants)
Female	106 89.8%
Male	12 10.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	30 25.4%
Not Hispanic or Latino	88 74.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.8%
Asian	1 0.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	19 16.1%
White	97 82.2%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	118 100%
Fitzpatrick Skin Type (Count of Participants)
Types I to III	65 55.1%
Types IV to VI	53 44.9%

Outcome Measures

1. Primary Outcome

Title	Non-inferiority of the Delta of the WSRS Score Between W24 and Baseline for TEOSYAL® RHA Ultra Deep Versus Perlane-L® for the Correction of Moderate to Severe Naso-Labial Folds Based on the Wrinkle Severity Rating Scale (WSRS) Score Assessed by the BLE.
Description	WSRS (Wrinkle Severity Rating Scale) is a validated 5-point scale with 1 being 'absent' and 5 being 'extreme'. BLE =Blinded Live Evaluator
Time Frame	Baseline and 24 weeks after last treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
Mean (95% Confidence Interval) [units on a scale]	-1.34	-1.16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TEOSYAL® RHA Ultra Deep, Perlane-L®
	Comments	Efficacy of TEOSYAL® RHA Ultra Deep versus control is analyzed in a non-inferiority statistical model using the 5-grade Wrinkle Severity Rating Scale (WSRS) as rated by the Blinded Live Evaluator at 24 weeks after baseline. The primary endpoint is the aesthetic improvement from pre-injection of the NLF at the side of the face treated with TEOSYAL® RHA Ultra Deep compared to the one at the side of the face treated with the control device, as assessed by the BLE at 24 weeks after baseline.
	Type of Statistical Test	Non-Inferiority
	Comments	A WSRS change of 1 grade is considered to be clinically significant. A difference of ≤0.5 grade between the two treatment groups (i.e., half of the clinically significant difference) = non-inferiority margin. The primary efficacy endpoint uses a paired-design and is analyzed by calculating two-sided confidence intervals of the mean difference between TEOSYAL® RHA UD and the control device, between the V1 enrollment visit (baseline) and V7 (24 weeks after baseline).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.34 to -0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	The decision is based on the upper limit of the 2-sided confidence interval for the difference for the change from baseline, between test and comparator treatment. For achieving non-inferiority, the upper confidence limit of a 95.0% CI must be ≤0.5

2. Secondary Outcome

Title	Post Injection Treatment Responses (From Common Treatment Responses (CTR) Diary) for Safety Evaluation of TEOSYAL® RHA Ultra Deep Versus Perlane-L®
Description	The subjects received a diary booklet and instructions for recording his/her observations of the Common Treatment Responses of the study treatments for the first 14 days after each treatment (initial, touch-up). The diary was discussed during each telephone follow-up visit. Subjects should 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 14-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. The table presents the number of subjects experiencing at least 1 Common Treatment Response (CTR)
Time Frame	During 14 days after initial treatment (D0) and touch-up (2 weeks)

Outcome Measure Data

Analysis Population Description

CTR are presented for the SAFT population (N=120) (see pre-assignment details) Number of patients for CTR after touch-up treatment are based on number of patients receiving Touch-up treatment (RHA-UD N=32/Perl N=47)

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	120	120
Bruising (initial treatment)	70 59.3%	72 NaN
Bruising (Touch-up)	17 14.4%	22 NaN
Discolouration (initial treatment)	50 42.4%	56 NaN
Discolouration (Touch-up)	9 7.6%	12 NaN
Firmness (initial treatment)	91 77.1%	93 NaN
Firmness (Touch-up)	24 20.3%	36 NaN
Itching (initial treatment)	30 25.4%	44 NaN
Itching (Touch-up)	4 3.4%	10 NaN
Lumps/Bumps (initial treatment)	81 68.6%	90 NaN
Lumps/Bumps (Touch-up)	18 15.3%	30 NaN
Pain (initial treatment)	66 55.9%	87 NaN
Pain (Touch-up)	16 13.6%	31 NaN
Redness (initial treatment)	84 71.2%	91 NaN
Redness (Touch-up)	17 14.4%	31 NaN
Swelling (initial treatment)	97 82.2%	104 NaN
Swelling (Touch-up)	27 22.9%	38 NaN
Tenderness (initial treatment)	90 76.3%	95 NaN
Tenderness (Touch-up)	21 17.8%	35 NaN

3. Secondary Outcome

Title	Assessment of Injection Site Pain (Visual Analog Scale) of TEOSYAL® RHA Ultra Deep Versus Perlane-L®
Description	VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain
Time Frame	During Injection and 5, 15, 30 minutes post-injection

Outcome Measure Data

Analysis Population Description

VAS are presented for the SAFT population (N=120) (see pre-assignment details) Number of patients for pain assessment after touch-up treatment are based on number of patients receiving Touch-up treatment

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	120	120
Initial injection mean pain during injection	23.43 (21.15)	23.85 (21.35)
Initial injection mean pain 5 min post-injection	6.22 (12.37)	5.33 (12.76)
Initial injection mean pain 15 min post-injection	2.67 (7.38)	2.82 (8.35)
Initial injection mean pain 30 min post-injection	1.83 (7.31)	1.65 (7.61)
Touch-up injection mean pain during injection	23.63 (23.06)	23.34 (19.32)
Touch-up injection mean pain 5 min post-injection	8.88 (14.46)	5.30 (8.39)
Touch-up injection mean pain 15 min post-injection	3.56 (6.48)	2.62 (4.88)
Touch-up injection mean pain 30 min post-injection	1.81 (4.49)	1.38 (3.17)

4. Secondary Outcome

Title	Delta of the WSRS Score Between W24,36,52 and 64 and Baseline for TEOSYAL® RHA Ultra Deep Versus Perlane-L® for the Correction of Moderate to Severe NLFs Based on the Wrinkle Severity Rating Scale (WSRS) Score Assessed by the Blinded Live Evaluator (BLE)
Description	WSRS (Wrinkle Severity Rating Scale) is a validated 5-point scale with 1 being 'absent' and 5 being 'extreme'.
Time Frame	Baseline and Weeks 24, 36, 52, 64

Outcome Measure Data

Analysis Population Description

Numbers of patients analyzed correspond to patients that have completed the visits and for which data were available (See participant flow)

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
W24 Delta from baseline	-1.34 (0.57)	-1.16 (0.62)
W36 Delta from baseline	-1.28 (0.63)	-1.12 (0.60)
W52 Delta from baseline	-1.23 (0.74)	-1.05 (0.67)
W64 Delta from baseline	-1.26 (0.71)	-1.11 (0.71)

5. Secondary Outcome

Title	Delta of the WSRS Score Between W2,4,12,24,36,52,64 and Baseline for TEOSYAL® RHA Ultra Deep Versus Perlane-L® for the Correction of Moderate to Severe NLFs Based on the Wrinkle Severity Rating Scale (WSRS) Score Assessed by the Treating Investigator (TI)
Description	WSRS (Wrinkle Severity Rating Scale) is a validated 5-point scale with 1 being 'absent' and 5 being 'extreme'.
Time Frame	Baseline and Weeks 2, 4, 12, 24, 36, 52, 64

Outcome Measure Data

Analysis Population Description

Numbers of patients analyzed correspond to patients that have completed the visits and for which data were available (See participant flow)

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
W2 Delta from baseline	-1.77 (0.60)	-1.51 (0.68)
W4 Delta from baseline	-1.85 (0.58)	-1.60 (0.63)
W12 Delta from baseline	-1.70 (0.78)	-1.34 (0.74)
W24 Delta from baseline	-1.45 (0.76)	-1.05 (0.76)
W36 Delta from baseline	-1.50 (0.78)	-1.16 (0.73)
W52 Delta from baseline	-1.38 (0.71)	-0.99 (0.67)
W64 Delta from baseline	-1.32 (0.82)	-1.03 (0.77)

6. Secondary Outcome

Title	Percentage of Responders Based on the Intra-individual Improvement of at Least One Grade in the Wrinkle Severity Rating Scale (WSRS) Compared to Baseline Assessed by the BLE
Description	A responder correspond to a subject with an intra-individual improvement of at least one grade in the WSRS compared to Baseline
Time Frame	Baseline and Weeks 24, 36, 52, 64

Outcome Measure Data

Analysis Population Description

Numbers of patients analyzed correspond to patients that have completed the visits and for which data were available (See participant flow)

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
W24	97.7	88.6
W36	90.7	87.2
W52	87.0	83.1
W64	89.2	84.6

7. Secondary Outcome

Title	Percentage of Responders Based on the Intra-individual Improvement of at Least One Grade in the Wrinkle Severity Rating Scale (WSRS) Compared to Baseline Assessed by the TI
Description	A responder correspond to a subject with an intra-individual improvement of at least one grade in the WSRS compared to baseline
Time Frame	Baseline and Weeks 2, 4, 12, 24, 36, 52, 64

Outcome Measure Data

Analysis Population Description

Numbers of patients analyzed correspond to patients that have completed the visits and for which data were available (See participant flow)

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
W2	97.7	93.2
W4	100.0	97.7
W12	95.5	88.6
W24	90.9	78.4
W36	90.7	83.7
W52	92.9	77.4
W64	83.1	76.1

8. Secondary Outcome

Title	Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) by the Blinded Live Evaluator (BLE)
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 was assessed independently.
Time Frame	Weeks 24, 36, 52, 64

Outcome Measure Data

Analysis Population Description

Numbers of patients analyzed correspond to patients that have completed the visits and for which data were available (See participant flow)

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
W24	84 71.2%	80 NaN
W36	80 67.8%	77 NaN
W52	65 55.1%	62 NaN
W64	52 44.1%	47 NaN

9. Secondary Outcome

Title	Number of Global Aesthetic Improvement (GAI) Responders (i.e., Scoring Either "Much Improved" or "Improved") on GAI Scale.
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 will be 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	Weeks 4, 12, 24, 36, 52, 64

Outcome Measure Data

Analysis Population Description

Numbers of patients analyzed correspond to patients that have completed the visits and for which data were available (See participant flow)

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
W4	87 73.7%	88 NaN
W12	87 73.7%	85 NaN
W24	82 69.5%	78 NaN
W36	81 68.6%	78 NaN
W52	77 65.3%	73 NaN
W64	64 54.2%	58 NaN

10. Secondary Outcome

Title	Subject's Perception of Treatment Effectiveness as Per the FACE-Q (NLF Domain) Questionnaire
Description	The FACE-Q measures the experience and outcomes of aesthetic facial procedures from the patient's perspective. 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 was instructed as follows: "These questions ask about how you look right now. 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 provided response. How deep your nasolabial fold are? How your nasolabial folds look when your face is relaxed (still)? How old your nasolabial folds make you look? How your nasolabial folds look when you smile? How your nasolabial folds look compared with other people your age? To calculate the FACE-Q, outcomes from all 5 questions were pooled and adapted to a scale to 100 units. Data were also transformed so that higher scores reflected a beneficial outcome.
Time Frame	Immediately post-injection, and weeks 2, 4, 12, 24, 36, 52, 64

Outcome Measure Data

Analysis Population Description

Numbers of patients analyzed correspond to patients that have completed the visits and for which data were available (See participant flow)

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
pre-treatment	24.7 (19.2)	25.7 (19.6)
W2	77.1 (23.3)	74.0 (23.9)
W4	84.3 (21.0)	81.2 (21.0)
W12	80.1 (22.3)	74.4 (25.0)
W24	70.9 (22.3)	66.1 (24.2)
W36	68.9 (25.0)	61.5 (25.5)
W52	72.0 (25.6)	65.9 (27.2)
W64	69.7 (24.0)	64.2 (27.5)

11. Secondary Outcome

Title	Subject's Satisfaction Score
Description	Subjective 5-point scale with 1 being 'very satisfied' and 5 being 'very dissatisfied'
Time Frame	Weeks 2, 4, 12, 24, 36, 52, 64

Outcome Measure Data

Analysis Population Description

Numbers of patients analyzed correspond to patients that have completed the visits and for which data were available (See participant flow)

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
W2	1.49 (0.61)	1.63 (0.88)
W4	1.28 (0.57)	1.31 (0.58)
W12	1.41 (0.62)	1.62 (0.83)
W24	1.53 (0.66)	1.79 (0.84)
W36	1.64 (0.75)	1.95 (0.96)
W52	1.54 (0.70)	1.77 (0.87)
W64	1.40 (0.60)	1.67 (0.90)

12. Secondary Outcome

Title	Volume to Obtain Optimal Cosmetic Result (Initial Treatment + Touch-up)
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
Mean (Standard Deviation) [mL]	1.79 (0.87)	1.75 (0.90)

13. Secondary Outcome

Title	Number of Subjects Receiving Touch-up Treatment
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
Count of Participants [Participants]	28 23.7%	38 NaN

14. Secondary Outcome

Title	Number of Subjects Receiving Re-treatment
Time Frame	Weeks 24, 36, 52, 64

Outcome Measure Data

Analysis Population Description

Numbers of patients analyzed correspond to patients that have completed the visits (See participant flow)

Arm/Group Title	TEOSYAL® RHA Ultra Deep	Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF	Injection of Perlane-L® into the controlateral NLF
Measure Participants	88	88
W24	6 5.1%	6 NaN
W36	3 2.5%	6 NaN
W52	12 10.2%	13 NaN
W64	49 41.5%	50 NaN

Adverse Events

Time Frame	64 weeks or 68 weeks for patients receiving a re-treatment at W64
Adverse Event Reporting Description	The TI assessed all AEs and recorded details of seriousness, severity, duration, and action taken with study device, and relationship to the study device. Adverse Events are presented for the SAFT population (N=120) (see pre-assignment details)
Arm/Group Title	TEOSYAL® RHA Ultra Deep		Perlane-L®
Arm/Group Description	Injection of TEOSYAL® RHA Ultra Deep into one NLF		Injection of Perlane-L® into the controlateral NLF
All Cause Mortality
	TEOSYAL® RHA Ultra Deep		Perlane-L®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	TEOSYAL® RHA Ultra Deep		Perlane-L®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/120 (2.5%)		3/120 (2.5%)
General disorders
Arthralgia	1/120 (0.8%)		1/120 (0.8%)
Diverticulitis	1/120 (0.8%)		1/120 (0.8%)
Infections and infestations
Lung Infection	1/120 (0.8%)		1/120 (0.8%)
Other (Not Including Serious) Adverse Events
	TEOSYAL® RHA Ultra Deep		Perlane-L®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/120 (62.5%)		74/120 (61.7%)
General disorders
Injection Lumps/Bumps	45/120 (37.5%)	52	34/120 (28.3%)	43
Injection site firmness	45/120 (37.5%)	52	34/120 (28.3%)	39
Injection site swelling	24/120 (20%)	28	17/120 (14.2%)	21
Tenderness	19/120 (15.8%)	22	12/120 (10%)	14
Injection site discolouration	13/120 (10.8%)	13	7/120 (5.8%)	7
Injection site erythema	8/120 (6.7%)	8	8/120 (6.7%)	8
Injection site haematoma	8/120 (6.7%)	8	4/120 (3.3%)	5
Injection site pain	6/120 (5%)	7	5/120 (4.2%)	5
Nervous system disorders
Headache	6/120 (5%)	9	6/120 (5%)	10
Skin and subcutaneous tissue disorders
Acne	5/120 (4.2%)	5	6/120 (5%)	6
Telangiectasia	5/120 (4.2%)	5	3/120 (2.5%)	3

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.