SUN-094 Long-Term Safety and Efficacy of Leuprorelin in Treating Central Precocious Puberty: A Large, Open-Label, Multicenter, Phase IV Study in China

BACKGROUND: Leuprorelin (Enantone®) is a gonadotropin-releasing hormone (GnRH) analogue used worldwide to treat central precocious puberty (CPP). This clinical trial aimed to evaluate the long-term safety and efficacy of leuprorelin in treating Chinese CPP children. Methods: This is the first, prospective, open-label, and multicenter study conducted from 2015 to 2018, in China. As a large interventional study, it included a four-week screening period, a 96-week treatment period, and a four-week safety follow-up period. Eligible subjects were treated with leuprorelin subcutaneously once every four weeks for 96 weeks. At the beginning of the study, subjects whose body weight ≥20 kg received a dose of 3.75 mg and those <20 kg received a dose of 1.88 mg and then the dose was allowed to be adjusted during the study based on subject’s condition and investigator’s judgment. The primary endpoint was the incidence of adverse events during treatment, and the secondary endpoint was the percentage of subjects who had regression or no progression in Tanner stage at Week 96 compared with baseline. Results: A total of 307 CPP patients from 11 Chinese medical centers received leuprorelin, of which 305 (99.3%) were girls and 2 were boys (0.7%), with a mean (±SD) age of 7.95±0.982 years and a mean height of 133.68±7.108 cm. Two hundred eighty-three (92.2%) patients completed the 96-week treatment period. Two hundred fifty-two patients (82.1%) reported treatment-emergent adverse events (TEAEs)—most of which (79.5%) were mild to moderate. Only 33 (10.7%) patients experienced TEAEs that were considered related to leuprorelin. The most frequent (>2%) drug-related TEAEs were injection site induration (4.6%, 14/307) and vaginal bleeding (2.3%, 7/305). After the 96-week treatment period, 83.5% female subjects had regression or no progression in Tanner stage compared with baseline (95% CI: 78.68%, 87.62%) and the 2 male subjects had progression of 1 point in Tanner stage genital score occurred at Week 12 and then remained stable throughout the study. By the end of the treatment period, the majority of subjects had decreased GnRH stimulated peak LH and FSH, as well as reduced sex hormone levels and bone age/chronological age ratio compared with baseline. The subjects also had increased predicted adult height and BMI after treatment. Conclusions: This Chinese study demonstrated that CPP was effectively treated in most patients who received leuprorelin (Enantone®) for nearly two years. Any drug-related adverse events were reported with low incidence (<5%) and were consistent with the known safety profile of leuprorelin. Leuprorelin was shown to be well tolerated and effective in the management of CPP in Chinese patients.