All effectiveness analyses were performed in the intent-to-treat (ITT) population (all randomized subjects) and safety was assessed in the safety population (all treated subjects or those randomized to the control group). In the primary analysis, GCRS responder rates at month 3 from baseline were compared using Fisher's exact test and presented as estimated responder rates, with two-sided 95% confidence intervals (CI) and P-value. Missing data at month 3 were imputed using the Baseline Observation Carried Forward method for the primary analysis. The difference in responder rates was calculated using the Wald Approximation with a continuity correction. A value of P<0.05 for the treatment difference was considered significant. The same analysis method was used for the secondary endpoint of GCRS responder rates at months 6, 9, and 12, except that analyses were performed on observed cases (no imputation of missing data). For the GAIS, a responder was defined as a subject with a rating of at least "improved." The time until subjects felt comfortable returning to social engagement was analyzed using Kaplan-Meier methods. All other variables were analyzed descriptively. Post-hoc analyses of responder rates and safety profiles were conducted with stratification by total injection volume (greater than or less than/equal to median volume). Statistical analyses were performed using the SAS 9.4 software.
RESULTS
Subjects and Treatment
In total, 140 subjects were randomized to HASHA (n=103) or no-treatment (n=37) and comprised the ITT population. One subject randomized in error to HASHA was not treated; 89% completed the study. The most common reasons for withdrawal were subject loss to follow up (6.4%) and withdrawal of consent (2.9%). At Month 12, 25 subjects in the no-treatment group chose to receive HASHA and these were included in the safety analysis.
Demographic and baseline characteristics were generally similar between the two groups (Table 1). Most subjects were female (97%) and white (84%) and the mean age was 42.0 years (range: 21 to 67). The most common Fitzpatrick skin types were III (46%), II (24%) and IV (24%). All subjects had GCRS Grade 1 or 2 chin retrusion at baseline.
The volume (mean +/- standard deviation) of injected product for the HASHA group was 2.10 +/- 0.85 mL at initial treatment (N=102) and 0.99 +/- 0.55 mL at touch-up treatment (N=73), with a total
injected volume of 2.81 +/- 1.20 mL. The median (range) total injected volume was 2.80 (0.70, 6.00) mL. The most common injection depth at initial treatment in the HASHA group was supraperiosteal (98%) and the most common injection method was bolus (76%).
Effectiveness
Improvement in Chin Retrusion (GCRS)
The primary objective to show HASHA superiority in improving chin retrusion was met. The Blinded Evaluator-assessed GCRS
