Trial Outcomes & Findings for RHA® 3 Versus Restylane-L® for Lip Augmentation (NCT NCT04540913)

Last Updated: 2025-02-03

Results Overview

A change in the TLFS ≥1 grade compared to pre-treatment will be considered clinically meaningful. The TLFS is a validated 5-point scale for assessing lip augmentation. Possible scores range from 1 (Very Thin) to 5 (Very Full). Change = (Week 12 - Baseline score).

Recruitment status

COMPLETED

Target enrollment

202 participants

Primary outcome timeframe

Week 12 after last treatment

Results posted on

2025-02-03

Participant Flow

Participant milestones

Participant milestones
Measure	RHA 3 Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks, optional retreatment at 36 or 52 Weeks. RHA 3: Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.	Control Device Injection of control device into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks. Comparator Product: a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Overall Study STARTED	153	49
Overall Study ITT Population	148	48
Overall Study mITT Population	137	44
Overall Study PP Population	127	42
Overall Study COMPLETED	139	46
Overall Study NOT COMPLETED	14	3

Reasons for withdrawal

Reasons for withdrawal
Measure	RHA 3 Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks, optional retreatment at 36 or 52 Weeks. RHA 3: Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.	Control Device Injection of control device into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks. Comparator Product: a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Overall Study Withdrawal by Subject	14	3

Baseline Characteristics

RHA® 3 Versus Restylane-L® for Lip Augmentation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RHA 3 n=153 Participants Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks, retreatment at 36 or 52 Weeks. RHA 3: Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.	Restylane- L n=49 Participants Injection of Restylane- L into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks. Restylane-L: Comparator Product, Restylane-L is a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.	Total n=202 Participants Total of all reporting groups
Age, Continuous	48.8 years STANDARD_DEVIATION 13.19 • n=99 Participants	48.5 years STANDARD_DEVIATION 11.69 • n=107 Participants	48.7 years STANDARD_DEVIATION 12.82 • n=206 Participants
Sex: Female, Male Female	151 Participants n=99 Participants	48 Participants n=107 Participants	199 Participants n=206 Participants
Sex: Female, Male Male	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Asian	4 Participants n=99 Participants	1 Participants n=107 Participants	5 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Black or African American	15 Participants n=99 Participants	2 Participants n=107 Participants	17 Participants n=206 Participants
Race (NIH/OMB) White	130 Participants n=99 Participants	45 Participants n=107 Participants	175 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	153 participants n=99 Participants	49 participants n=107 Participants	202 participants n=206 Participants
Fitzpatrick Skin Type [1] Type I-III	114 Participants n=99 Participants	35 Participants n=107 Participants	149 Participants n=206 Participants
Fitzpatrick Skin Type [1] Type IV-VI	39 Participants n=99 Participants	14 Participants n=107 Participants	53 Participants n=206 Participants

PRIMARY outcome

Timeframe: Week 12 after last treatment

Population: Primary endpoint on the mITT population

Outcome measures

Outcome measures
Measure	RHA 3 n=137 Participants Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks, optional retreatment at 36 or 52 Weeks. RHA 3: Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.	Control Device n=44 Participants Injection of control device into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks. Control Device: a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Change in TLFS Score (Teoxane Lip Fullness Scale) Between Baseline and Week 12 After Last Treatment of RHA®3 Versus Control Device, as Assessed by the BLE	1.0 score on a scale Standard Deviation 0.65	0.8 score on a scale Standard Deviation 0.70

SECONDARY outcome

Timeframe: Weeks 36 and 52 after last treatment, week 4 after re-treatment

Population: mITT population

A change in the TLFS ≥1 grade compared to pre-treatment will be considered clinically meaningful. The TLFS is a validated 5-point static scale for assessing lip augmentation. Possible scores range from 1 (Very Thin) to 5 (Very Full).

Outcome measures

Outcome measures
Measure	RHA 3 n=137 Participants Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks, optional retreatment at 36 or 52 Weeks. RHA 3: Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.	Control Device n=44 Participants Injection of control device into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks. Control Device: a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Change From Baseline in TLFS Score as Assessed by the BLE at Visit 5 (Weeks 24 After Last Treatment), 6 (Weeks 36 After Last Treatment), 7 (Week 52 After Last Treatment) if Applicable, and Re-treatment (4 Weeks After Re-treatment) Week 36 after last treatment	0.7 score on a scale Standard Deviation 0.65	0.5 score on a scale Standard Deviation 0.63
Change From Baseline in TLFS Score as Assessed by the BLE at Visit 5 (Weeks 24 After Last Treatment), 6 (Weeks 36 After Last Treatment), 7 (Week 52 After Last Treatment) if Applicable, and Re-treatment (4 Weeks After Re-treatment) Week 52 after last treatment	0.5 score on a scale Standard Deviation 0.64	0.1 score on a scale Standard Deviation 0.63
Change From Baseline in TLFS Score as Assessed by the BLE at Visit 5 (Weeks 24 After Last Treatment), 6 (Weeks 36 After Last Treatment), 7 (Week 52 After Last Treatment) if Applicable, and Re-treatment (4 Weeks After Re-treatment) Re-treatment: 4weeks post re-treatment at week 36	1.0 score on a scale Standard Deviation 0.82	0.9 score on a scale Standard Deviation 0.74
Change From Baseline in TLFS Score as Assessed by the BLE at Visit 5 (Weeks 24 After Last Treatment), 6 (Weeks 36 After Last Treatment), 7 (Week 52 After Last Treatment) if Applicable, and Re-treatment (4 Weeks After Re-treatment) Re-treatment: 4 weeks post re-treatment at week 52	1.1 score on a scale Standard Deviation 0.74	0.9 score on a scale Standard Deviation 0.66

SECONDARY outcome

Timeframe: Weeks 12, 36, 52 after last treatment, week 4 after re-treatment

Population: mITT population

A responder will be defined as a subject who has a ≥1 grade improvement on the TLFS. The TLFS is a validated 5-point static scale for assessing lip augmentation. Possible scores range from 1 (Very Thin) to 5 (Very Full).

Outcome measures

Outcome measures
Measure	RHA 3 n=137 Participants Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks, optional retreatment at 36 or 52 Weeks. RHA 3: Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.	Control Device n=44 Participants Injection of control device into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks. Control Device: a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Responder Rate Calculated Using TLFS Assessed by the BLE Re-treatment: 4weeks post re-treatment at week 36	18 Participants	7 Participants
Responder Rate Calculated Using TLFS Assessed by the BLE Week 12 after last treatment	105 Participants	29 Participants
Responder Rate Calculated Using TLFS Assessed by the BLE Week 36 after last treatment	81 Participants	22 Participants
Responder Rate Calculated Using TLFS Assessed by the BLE Week 52 after last treatment	38 Participants	6 Participants
Responder Rate Calculated Using TLFS Assessed by the BLE Re-treatment: 4weeks post re-treatment at week 52	49 Participants	13 Participants

SECONDARY outcome

Timeframe: Weeks 12, 36, 52 after last treatment and 4 week after re-treatment.

Population: mITT population

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).

Outcome measures

Outcome measures
Measure	RHA 3 n=137 Participants Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks, optional retreatment at 36 or 52 Weeks. RHA 3: Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.	Control Device n=44 Participants Injection of control device into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks. Control Device: a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Number of Subjects "Satisfied" or "Very Satisfied" With Study Treatment Using the Subject Satisfaction Scale at Weeks 12, 36, 52 After Last Treatment and 4 Weeks After Re-treatment. Week 12 after last treatment	113 Participants	33 Participants
Number of Subjects "Satisfied" or "Very Satisfied" With Study Treatment Using the Subject Satisfaction Scale at Weeks 12, 36, 52 After Last Treatment and 4 Weeks After Re-treatment. Week 36 after last treatment	108 Participants	27 Participants
Number of Subjects "Satisfied" or "Very Satisfied" With Study Treatment Using the Subject Satisfaction Scale at Weeks 12, 36, 52 After Last Treatment and 4 Weeks After Re-treatment. Week 52 after last treatment	67 Participants	16 Participants
Number of Subjects "Satisfied" or "Very Satisfied" With Study Treatment Using the Subject Satisfaction Scale at Weeks 12, 36, 52 After Last Treatment and 4 Weeks After Re-treatment. Re-treatment: 4 weeks post re-treatment at week 36	22 Participants	9 Participants
Number of Subjects "Satisfied" or "Very Satisfied" With Study Treatment Using the Subject Satisfaction Scale at Weeks 12, 36, 52 After Last Treatment and 4 Weeks After Re-treatment. Re-treatment: 4 weeks post re-treatment at week 52	54 Participants	15 Participants

SECONDARY outcome

Timeframe: Change from Baseline at Weeks 12, 36, 52 after last treatment and 4 week after re-treatment.

Population: mITT population

The FACE-Q measures the experience and outcomes of aesthetic facial procedures from the patient's perspective. The FACE-Q questionnaire is composed of 10 questions with a score linked to answers (1 being "Very Dissatisfied" and 4 being "Very Satisfied"). 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 lips in mind, in the past week, how satisfied or dissatisfied have been with:", and will provide response. To calculate the FACE-Q, outcomes from all 10 questions were pooled, data were transformed so that higher scores reflected a superior (positive) outcome, and adapted to a scale of 100 units (i.e. worst/lowest score = 0, best/highest score = 100).

Outcome measures

Outcome measures
Measure	RHA 3 n=137 Participants Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks, optional retreatment at 36 or 52 Weeks. RHA 3: Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.	Control Device n=44 Participants Injection of control device into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks. Control Device: a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Lips" FACE-Q \| Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. Week 12 after last treatment	50.6 score on a scale Standard Deviation 25.58	46.1 score on a scale Standard Deviation 26.71
Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Lips" FACE-Q \| Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. Week 36 after last treatment	40.9 score on a scale Standard Deviation 29.11	31.8 score on a scale Standard Deviation 30.76
Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Lips" FACE-Q \| Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. Week 52 after last treatment	36.2 score on a scale Standard Deviation 27.56	25.1 score on a scale Standard Deviation 30.60
Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Lips" FACE-Q \| Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. Re-treatment: 4weeks post re-treatment at week 36	57.4 score on a scale Standard Deviation 24.42	55.7 score on a scale Standard Deviation 19.7
Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Lips" FACE-Q \| Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. Re-treatment: 4weeks post re-treatment at week 52	56.0 score on a scale Standard Deviation 23.8	51.9 score on a scale Standard Deviation 20.45

SECONDARY outcome

Timeframe: Weeks 12, 36, 52 after last treatment and 4 week after re-treatment.

Population: mITT population

The FACE-Q measures the experience and outcomes of aesthetic facial procedures from the patient's perspective. The FACE-Q questionnaire is composed of 6 questions with a score linked to answers (1 being "Definitely disagree" and 4 being "Definitely agree"). The subject will be instructed as follows: "We would like to know how you feel about your most recent procedure. For each question, select only one answer. Please indicate how much you agree or disagree with each statement:", and will provide response. To calculate the FACE-Q, outcomes from all 16questions were pooled, data were transformed so that higher scores reflected a superior (positive) outcome, and adapted to a scale of 100 units (i.e. worst/lowest score = 0, best/highest score = 100).

Outcome measures

Outcome measures
Measure	RHA 3 n=137 Participants Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks, optional retreatment at 36 or 52 Weeks. RHA 3: Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.	Control Device n=44 Participants Injection of control device into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks. Control Device: a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Outcome" FACE-Q \| Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. Week 12 after last treatment	77.2 score on a scale Standard Deviation 22.65	71.1 score on a scale Standard Deviation 29.64
Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Outcome" FACE-Q \| Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. Week 36 after last treatment	73.8 score on a scale Standard Deviation 26.03	61.9 score on a scale Standard Deviation 33.62
Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Outcome" FACE-Q \| Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. Week 52 after last treatment	75.6 score on a scale Standard Deviation 24.08	61.6 score on a scale Standard Deviation 30.65
Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Outcome" FACE-Q \| Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. Re-treatment: 4weeks post re-treatment at week 36	81.0 score on a scale Standard Deviation 19.43	76.8 score on a scale Standard Deviation 22.84
Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Outcome" FACE-Q \| Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. Re-treatment: 4weeks post re-treatment at week 52	82.4 score on a scale Standard Deviation 20.61	75.6 score on a scale Standard Deviation 27.5

SECONDARY outcome

Timeframe: Weeks 12, 36, 52 after last treatment, and 4 weeks after re-treatment

Population: mITT population

The Global Aesthetic Improvement (GAI) is a subjective, balanced, 5-point dynamic scale assessing cosmetic improvement. Possible scores range from "much improved", "improved", "no change", "worse", to "much worse". The GAI will be assessed using the baseline photograph.

Outcome measures

Outcome measures
Measure	RHA 3 n=137 Participants Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks, optional retreatment at 36 or 52 Weeks. RHA 3: Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.	Control Device n=44 Participants Injection of control device into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks. Control Device: a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) Scale by the BLE. Week 12 after last treatment	134 Participants	41 Participants
Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) Scale by the BLE. Week 36 after last treatment	113 Participants	29 Participants
Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) Scale by the BLE. Week 52 after last treatment	58 Participants	11 Participants
Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) Scale by the BLE. Re-treatment: 4weeks post re-treatment at week 36	21 Participants	8 Participants
Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) Scale by the BLE. Re-treatment: 4weeks post re-treatment at week 52	58 Participants	17 Participants

Adverse Events

RHA 3

Serious events: 0 serious events

Other events: 75 other events

Deaths: 0 deaths

Restylane- L

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	RHA 3 n=153 participants at risk Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Touch up treatment provided at 4 Weeks, retreatment at 36 or 52 Weeks. RHA 3: Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.	Restylane- L n=49 participants at risk Injection of Restylane- L into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Touch up treatment provided at 4 Weeks. Restylane-L: Comparator Product, Restylane-L is a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Nervous system disorders Intracranial aneurysm	0.00% 0/153 • 36 to 44 (for patients receiving re-treatment) weeks for subjects who did not consent to study extension. 52 to 60 (for patients receiving re-treatment) weeks for subjects who consented to the study extension	2.0% 1/49 • Number of events 1 • 36 to 44 (for patients receiving re-treatment) weeks for subjects who did not consent to study extension. 52 to 60 (for patients receiving re-treatment) weeks for subjects who consented to the study extension

Other adverse events

Additional Information

Clinical Research Scientist

TEOXANE SA

Phone: +41(0) 22 344 96 36

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60