Restylane (Galderma, Uppsala, Sweden) with a G' of 701 Pa (0.1 Hz) and Restylane (Galderma) with a G' of 799 Pa (0.1 Hz). A new HA injectable, Restylane ShaypeTM (HASHA; Galderma), has been developed for lower face shaping and to be injected on bone. HASHA uses the new NASHA-HDTM (High Definition) technology, an evolution of the NASHA platform, using the same low modification and mild processing as NASHA but with increased efficiency of the crosslinking process. This results in HASHA being an even stronger/firmer product (G' of 916 Pa [0.1 Hz]) with high HA concentration (25 mg/mL). In addition, it is a stable product with high resistance to degradation by heat.
Here, we report the results from a pivotal clinical investigation evaluating the effectiveness and safety of HASHA, compared to a no-treatment control, for augmentation and correction of retrusion in the chin region.
MATERIALS AND METHODS
Study Design
This was a prospective, randomized, evaluator-blinded, no-treatment controlled, parallel-group, multicenter study, conducted at nine centers in Canada, between January 2021 and June 2022. Subjects were healthy men or non-pregnant women aged 18 years or greater, with mild (Grade 1) or moderate (Grade 2) chin retrusion at baseline, as assessed by a treatment-blinded evaluator using the Galderma Chin Retrusion Scale (GCRS, where Grade 0 = none, Grade 1 = mild, Grade 2 = moderate, and Grade 3 = severe retrusion). Exclusion criteria included a history of multiple or severe allergies, known or previous allergy/hypersensitivity to local anesthetics; prior procedures in the lower facial region (eg, surgery, permanent/semi-permanent implants); HA or collagen filler treatments in the lower face within the last 12 months; energy-based aesthetic procedures (eg, lasers), mechanical or chemical procedures, botulinum toxin, or cryotherapy in the lower face within the last 6 months; deoxycholic acid treatment in the submental region within the last 6 months; the presence of disease or lesions near the area to be treated (eg, inflammation, infections, acne, psoriasis, scars, cancer or precancer); other underlying conditions (eg, HIV or bleeding disorders) or recent or concomitant medications (eg, anticoagulants, immunosuppressants, chemotherapy, topical facial or systemic corticosteroids) that could expose the subject to undue risk. The study was approved by the Institutional Review Boards at each site and was conducted in accordance with Good Clinical Practice and the Declaration of Helsinki. All subjects provided written, informed consent before starting the study.
Treatment and Follow-up
Subjects were randomized (3:1) to either HASHA (Restylane Shaype, Galderma, Uppsala, Sweden) injection with the initial treatment given on Day 1 or no-treatment control. HASHA gel (25 mg/mL HA plus 3 mg/mL lidocaine hydrochloride) was administered using a 1 mL syringe with a 27-gauge, 3/4-inch, ultra-thin wall needle into the chin and surrounding regions. The injection was made into the deep subcutaneous tissue or supraperiosteal plane, as chosen by the treating investigator, with additional local anesthetic if needed. On Day 1, subjects received up to 4 mL HASHA for optimal retrusion correction, defined as 1-point or greater improvement from baseline on the GCRS and the best correction that could be achieved (investigator and subject agreement). An optional touch-up treatment with up to 2 mL HASHA was allowed at month 1, if necessary to obtain optimal aesthetic improvement of the chin. Post-treatment procedures included gently massaging the treated area, applying an ice pack, and providing subjects with guidance on standard post-treatment care. Subjects were followed for up to 12 months from baseline. Subjects in the control group were offered HASHA treatment at the month 12 visit; where accepted, these subjects were followed for one month after injection.
The secondary objectives were to assess effectiveness and subject satisfaction up to month 12 after treatment. These included Blinded Evaluator-assessed GCRS responder rates, investigator- and subject-assessed aesthetic improvement using the Global Aesthetic Improvement Scale (GAIS; a 7-point scale ranging from "very much worse" to "very much improved"), and a subject-completed Satisfaction Questionnaire. Subjects also completed a 4-week diary, starting on the day of the initial or touch-up treatment, which included documenting the time in hours from injection until they felt comfortable returning to social engagements, and the occurrence of the following predefined, expected post-treatment events (bruising, redness, pain, tenderness, itching, or swelling in the treated area; rated as tolerable, affecting daily activities, or disabling). Investigator-reported safety included documentation of adverse events (AEs) and physical examinations evaluating changes in hair growth in the chin region throughout the study.
Statistical Analysis
A sample size of 140 subjects (randomized 3:1 to HASHA or no treatment) based on a power calculation was needed to achieve approximately 90% power to demonstrate a difference between groups, assuming GCRS responder rates of 70% in the HASHA group and 35% in the no-treatment control group, using a two-sided significance level of 0.05.
