IMPE Abstracts

Background: Gonadotropin-releasing hormone (GnRH) analogs are widely used in the treatment of central precocious puberty (CPP). Triptorelin is available as 1-month and 3-month prolonged release (PR) formulations, but only the former is approved for CPP in China. This phase 3 study assessed whether the effectiveness of triptorelin 3-month PR formulation in Chinese children with CPP was comparable to overseas children.

Methods: In this 6-month open-label multicenter single-arm prospective study (NCT04736602), Chinese children with CPP received two doses of triptorelin pamoate 15 mg (Diphereline®, Ipsen; delivering 11.25 mg of triptorelin) on Day 1 and Month 3. The primary endpoint was the proportion of children with luteinizing hormone (LH) suppression, defined as stimulated peak LH ≤ 3 IU/L after GnRH stimulation at Month 3. Secondary endpoints included changes from baseline in hormone levels, pubertal stage, auxological parameters, bone age, uterine length (girls) or testicular volume (boys) and treatment-emergent adverse events (TEAEs).

Results: Overall, 32 children (mean age ± standard deviation, 7.6 ± 0.8 years; 90.6% girls) were enrolled; 31 and 30 children completed assessments at Months 3 and 6, respectively. LH suppression to prepubertal levels (≤ 3 IU/L) after GnRH stimulation was observed in 100% and 93.5% of children at Months 3 and 6, respectively. Basal and peak LH and follicle-stimulating hormone (FSH) levels were both substantially suppressed at Months 3 and 6 in girls and boys. At Month 3, all patients showed suppression of sex hormones to within the prepubertal range (girls: estradiol ≤ 20 pg/mL; boys: testosterone ≤ 0.3 ng/mL). Sex hormone suppression was evident in 30 children at Month 6. At Month 6, 92.9% of girls had stable breast development, and all boys had stable genital development. Compared with baseline, there was a mean decrease in growth velocity at Month 3 (−0.895 cm/year) and Month 6 (−3.769 cm/year), and there was a mean decrease in the difference between bone and chronological ages from baseline (2.85 years) to Month 6 (2.40 years). In girls, uterine length was stable or reduced from baseline to Month 6, and in boys, testicular volume was reduced. In total, 22 children (68.8%) reported 48 TEAEs; there were no serious AEs, no TEAE-related discontinuations and no deaths.

Conclusion(s): The triptorelin 3-month PR formulation demonstrated similar efficacy to that in overseas children with CPP and an acceptable safety profile, supporting it as a viable treatment option in Chinese children.