Long-term Safety, Efficacy, and PROs: Phase 3 Study of Leuprolide Acetate 6-month IM Depot in Central Precocious Puberty.

Context: The long-term safety and efficacy of leuprolide acetate (LA) intramuscular (IM) depot in children with central precocious puberty (CPP) have not been examined. Objective: We evaluated the 144-week efficacy and safety of LA IM depot with 6-month dosing frequency for the treatment of CPP. Methods: Children with CPP received 45 mg LA IM depot in a phase 3, single-arm study (NCT03695237) that enrolled both treatment-naive (n = 27) and previously treated (n = 18) children (age: 7.8 ± 1.27 years). Outcomes included suppression of peak-stimulated LH (<4 mIU/mL), basal estradiol (<20 pg/mL), and testosterone (<30 ng/dL) and physical puberty signs (based on nonmissing data), height-related outcomes, patient/parent-reported outcomes, and safety. Results: Peak-stimulated LH was suppressed in 93%, 95%, 100%, and 100% of children at weeks 72, 96, 120, and 144, respectively; basal sex hormones were suppressed in all children. Most children had pubertal signs suppressed during long-term treatment (Tanner staging, weeks 72-144, girls: 86.4-94.9%; boys, 50.0-75.0%). After week 48, mean incremental height velocity remained relatively stable, and mean ratio of bone age to chronological age was 1.2. At week 144, mean annualized change from baseline in predicted adult height (PAH) was 1.4 cm/year, and mean absolute PAH in girls improved compared with mid-parental height. Health-related quality of life was maintained. No new related safety concerns were identified. Conclusion: Six-month LA IM depot for 144 weeks demonstrated a sustained inhibition of the GnRH axis in children with CPP with an acceptable safety profile. Health-related quality of life was maintained, and PAH improved during ∼3 years of treatment.