INTRODUCTION
Cellulite is a topographic and localized skin condition, commonly found on the posterolateral thighs, buttocks, and abdomen, and related to collagen and elastic tissue degeneration in the dermis and hypodermis.1 With age, collagen production in the body decreases, resulting in the visible signs of aging2 such as an increase in skin laxity, which is a significant aggravating factor for cellulite.3
Numerous treatments have been proposed to treat cellulite,1,4-6 all with varying efficacy7 and most with modest and temporary results.8 In addition, most treatments do not target the underlying structural causes of cellulite or require very advanced surgical training.9
Sculptra® (Galderma, PLLA-SCA™) is a soft tissue injectable containing microparticles of poly-L-lactic acid, a biocompatible, biodegradable, synthetic polymer from the alpha-hydroxy-acid family. It works as a regenerative biostimulator, inducing collagen and elastin synthesis over time to help restore the skin’s inner structure.10 In pivotal trials, PLLA-SCA has recently demonstrated effectiveness and safety for correction of cheek wrinkles,11 and correction of midface (NCT04132518), enabling label extension for these facial indications. Further to facial aesthetic treatment, there is increased interest in using PLLA-SCA for non-facial indications,12-15 with current certification in accordance with the Medical Device Regulation for PLLA-SCA use in décolletage, posterior thighs (cellulite), upper arms, and the gluteal area.
Based on the theory that a stronger skin structure, with a decrease in skin laxity and an increase in dermal thickness, could reduce the appearance of cellulite, this clinical study was performed to investigate the effectiveness and safety of PLLA-SCA for the improvement in appearance of cellulite in the posterior thighs.
Numerous treatments have been proposed to treat cellulite,1,4-6 all with varying efficacy7 and most with modest and temporary results.8 In addition, most treatments do not target the underlying structural causes of cellulite or require very advanced surgical training.9
Sculptra® (Galderma, PLLA-SCA™) is a soft tissue injectable containing microparticles of poly-L-lactic acid, a biocompatible, biodegradable, synthetic polymer from the alpha-hydroxy-acid family. It works as a regenerative biostimulator, inducing collagen and elastin synthesis over time to help restore the skin’s inner structure.10 In pivotal trials, PLLA-SCA has recently demonstrated effectiveness and safety for correction of cheek wrinkles,11 and correction of midface (NCT04132518), enabling label extension for these facial indications. Further to facial aesthetic treatment, there is increased interest in using PLLA-SCA for non-facial indications,12-15 with current certification in accordance with the Medical Device Regulation for PLLA-SCA use in décolletage, posterior thighs (cellulite), upper arms, and the gluteal area.
Based on the theory that a stronger skin structure, with a decrease in skin laxity and an increase in dermal thickness, could reduce the appearance of cellulite, this clinical study was performed to investigate the effectiveness and safety of PLLA-SCA for the improvement in appearance of cellulite in the posterior thighs.
MATERIALS AND METHODS
Study Design
This was a 12-month, prospective study (NCT05064761) conducted at one center in Canada between November 2021 and February 2023. The study complied with Good Clinical Practice and the ethical principles of the Declaration of Helsinki and its amendments. Ethical approval was obtained from the Institutional Review Board prior to study start, and all subjects provided signed written informed consent.
The primary and secondary objectives of the study were to evaluate the effectiveness of PLLA-SCA to improve the appearance of cellulite in the posterior thighs. The primary and secondary effectiveness endpoints are listed under assessments. Another study objective was to evaluate the safety of PLLA-SCA treatment of the posterior thighs to improve the appearance of cellulite.
Study Population
It was planned to include approximately 30 non-pregnant, immune-competent women, ≥18 years, with Grade 2–4 cellulite severity on the Galderma Posterior Thigh Cellulite Scale (GTCS) on both thighs (symmetrical grading not required), characterized by superficial to moderately deep depressions with undulations. Additional inclusion criteria included a BMI ≥18.5 and ≤25 kg/m2 and that the subjects could benefit from treatment to improve the appearance of cellulite in the opinion of the Principal Investigator.
Study Treatment and Visits
All enrolled subjects were to receive a single regimen of PLLASCA, comprising three treatment sessions each spaced one month (+2 weeks) apart: at baseline, month 1, and month 2.
Each vial of 150 mg dry powder PLLA-SCA was reconstituted with 17 mL using sterile water for injection, with the addition of 1 mL 2% lidocaine hydrochloride, prior to use. A maximum of 3 vials, ie, up to 54 mL per thigh (in total 6 vials in both thighs), were administered per treatment session. Subjects were injected to achieve optimal correction, as agreed upon by the treating investigator and the subject. The study product was injected subcutaneously in the deep dermis or subdermal region using 25-Gauge 1.5-inch BD needles, evenly spread over the entire treatment area of both posterior thighs with a fanning, asterisk, or short linear threading technique with a distance of 1-2 cm using 0.05–0.1 mL per injection point. The treatment area was delimited by the infragluteal fold (superior border), the iliotibial band – posterior border (lateral border), the gracilis muscle – posterior border (medial border), and 2/3 from the infragluteal fold to the popliteal crease (inferior border).
Additional follow-up visits were conducted at months 6, 9, and 12.
Assessments
Global Aesthetic Improvement Scale (GAIS), primary and secondary endpoints
The 7-graded Global Aesthetic Improvement Scale (GAIS) was used to assess the aesthetic improvement of cellulite in the treatment area compared to a photograph taken at baseline before treatment, with response options: "Very much improved", "Much improved", "Improved", "No change", "Worse", "Much worse", and "Very much worse". The treating investigator assessed the aesthetic improvement live by comparison with the baseline photograph. Subjects assessed aesthetic improvement by comparing photographs taken at the current visit with photographs taken at baseline before treatment. The right and left posterior thighs were assessed separately. The primary endpoint was the treating investigator-assessed GAIS responder rate at month 9, with responder defined as at least “Improved” in both thighs. Secondary endpoints included GAIS responder rates assessed by the treating investigator at months 1, 2, 6, and 12, and by subjects at all visits, with responder defined as at least "Improved".
Galderma Posterior Thigh Cellulite Scale (GTCS), secondary endpoints
The GTCS at rest is a 5-graded, photographic-based scale assessing the severity of depressions and undulations associated with cellulite in the thigh. The five scores represent visibly distinct degrees of appearance, where 1=smooth skin with up to a few superficial undulations, 2=few superficial depressions with undulations, 3=shallow depressions with undulations, 4=moderately deep depressions with undulations covering the majority of the posterior thigh, and 5=deep depressions with undulations covering the majority of the posterior thigh with or without redundant skin bulges. Assessments were performed before and after treatment. Secondary endpoints included responder rates on the GTCS for each thigh at all post-baseline visits, as assessed live by the treating investigator. Responders were defined as subjects with ≥1 grade improvement from baseline.
Skin laxity assessment, secondary endpoints
Skin laxity change from baseline at months 6, 9, and 12 were secondary endpoints, assessed live by the treating investigator aided by photographs taken at baseline before treatment. The following aspects were reported for each thigh separately: "Has the skin laxity improved after treatment?" and "Does the skin appear tighter after treatment?".
Subject satisfaction questionnaire (SSQ), secondary endpoints
Subjects reported satisfaction with treatment results by responding to a Subject Satisfaction Questionnaire (SSQ) comprising 12 questions. The percentages of subjects in each response category were secondary endpoints.
This was a 12-month, prospective study (NCT05064761) conducted at one center in Canada between November 2021 and February 2023. The study complied with Good Clinical Practice and the ethical principles of the Declaration of Helsinki and its amendments. Ethical approval was obtained from the Institutional Review Board prior to study start, and all subjects provided signed written informed consent.
The primary and secondary objectives of the study were to evaluate the effectiveness of PLLA-SCA to improve the appearance of cellulite in the posterior thighs. The primary and secondary effectiveness endpoints are listed under assessments. Another study objective was to evaluate the safety of PLLA-SCA treatment of the posterior thighs to improve the appearance of cellulite.
Study Population
It was planned to include approximately 30 non-pregnant, immune-competent women, ≥18 years, with Grade 2–4 cellulite severity on the Galderma Posterior Thigh Cellulite Scale (GTCS) on both thighs (symmetrical grading not required), characterized by superficial to moderately deep depressions with undulations. Additional inclusion criteria included a BMI ≥18.5 and ≤25 kg/m2 and that the subjects could benefit from treatment to improve the appearance of cellulite in the opinion of the Principal Investigator.
Study Treatment and Visits
All enrolled subjects were to receive a single regimen of PLLASCA, comprising three treatment sessions each spaced one month (+2 weeks) apart: at baseline, month 1, and month 2.
Each vial of 150 mg dry powder PLLA-SCA was reconstituted with 17 mL using sterile water for injection, with the addition of 1 mL 2% lidocaine hydrochloride, prior to use. A maximum of 3 vials, ie, up to 54 mL per thigh (in total 6 vials in both thighs), were administered per treatment session. Subjects were injected to achieve optimal correction, as agreed upon by the treating investigator and the subject. The study product was injected subcutaneously in the deep dermis or subdermal region using 25-Gauge 1.5-inch BD needles, evenly spread over the entire treatment area of both posterior thighs with a fanning, asterisk, or short linear threading technique with a distance of 1-2 cm using 0.05–0.1 mL per injection point. The treatment area was delimited by the infragluteal fold (superior border), the iliotibial band – posterior border (lateral border), the gracilis muscle – posterior border (medial border), and 2/3 from the infragluteal fold to the popliteal crease (inferior border).
Additional follow-up visits were conducted at months 6, 9, and 12.
Assessments
Global Aesthetic Improvement Scale (GAIS), primary and secondary endpoints
The 7-graded Global Aesthetic Improvement Scale (GAIS) was used to assess the aesthetic improvement of cellulite in the treatment area compared to a photograph taken at baseline before treatment, with response options: "Very much improved", "Much improved", "Improved", "No change", "Worse", "Much worse", and "Very much worse". The treating investigator assessed the aesthetic improvement live by comparison with the baseline photograph. Subjects assessed aesthetic improvement by comparing photographs taken at the current visit with photographs taken at baseline before treatment. The right and left posterior thighs were assessed separately. The primary endpoint was the treating investigator-assessed GAIS responder rate at month 9, with responder defined as at least “Improved” in both thighs. Secondary endpoints included GAIS responder rates assessed by the treating investigator at months 1, 2, 6, and 12, and by subjects at all visits, with responder defined as at least "Improved".
Galderma Posterior Thigh Cellulite Scale (GTCS), secondary endpoints
The GTCS at rest is a 5-graded, photographic-based scale assessing the severity of depressions and undulations associated with cellulite in the thigh. The five scores represent visibly distinct degrees of appearance, where 1=smooth skin with up to a few superficial undulations, 2=few superficial depressions with undulations, 3=shallow depressions with undulations, 4=moderately deep depressions with undulations covering the majority of the posterior thigh, and 5=deep depressions with undulations covering the majority of the posterior thigh with or without redundant skin bulges. Assessments were performed before and after treatment. Secondary endpoints included responder rates on the GTCS for each thigh at all post-baseline visits, as assessed live by the treating investigator. Responders were defined as subjects with ≥1 grade improvement from baseline.
Skin laxity assessment, secondary endpoints
Skin laxity change from baseline at months 6, 9, and 12 were secondary endpoints, assessed live by the treating investigator aided by photographs taken at baseline before treatment. The following aspects were reported for each thigh separately: "Has the skin laxity improved after treatment?" and "Does the skin appear tighter after treatment?".
Subject satisfaction questionnaire (SSQ), secondary endpoints
Subjects reported satisfaction with treatment results by responding to a Subject Satisfaction Questionnaire (SSQ) comprising 12 questions. The percentages of subjects in each response category were secondary endpoints.
