ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 7.3 | DOI: 10.1530/ey.18.7.3

ESPEYB18 7. Puberty Clinical Guidance (7 abstracts)

7.3. Phase 3 trial of a small-volume subcutaneous 6-month duration leuprolide acetate treatment for central precocious puberty

Klein KO , Freire A , Gryngarten MG , Kletter GB , Benson M , Miller BS , Dajani TS , Eugster EA & Mauras N

J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3660–71. 10.1210/clinem/dgaa479.

In brief: This phase 3 multi-centre, open-label, single-arm study explores the efficacy, pharmacokinetics and safety of 6-monthly 45-mg subcutaneous leuprolide acetate in 59 patients with central precocious puberty (CPP). Six-monthly leuprolide acetate appears to be a promising treatment to suppress pubertal hormones and progression of secondary sexual features.

Comment: CPP is classically treated with GnRH agonists. Available treatments include intramuscular leuprolide acetate injections, intramuscular triptorelin injections and subcutaneous histrelin acetate implants (1).

This phase 3 study evaluated the pharmacokinetics, safety and efficacy of 6-monthly 45-mg subcutaneous leuprolide acetate. Fifty-nine patients (57 girls and 2 boys) received 2 injections of leuprolide acetate and were evaluated at weeks 0, 24 and 48. Post-stimulation LH was suppressed (<4 IU/L) in 87% and 88% of children at weeks 24 and 48, respectively. Growth velocity regressed in >50% of patients at weeks 24 and 48, and average bone age advancement slightly but significantly regressed. Breast development regressed in almost all girls (55/57) and genital development regressed from G3 to G2 after 2 injections in both treated boys. An initial burst release of leuprolide was reported between 1 and 6 hours post-injection, followed by stable levels from weeks 12 to 44. Injections were well tolerated and no withdrawal was reported. Two serious adverse effects were documented (wheezing and rash) but considered unrelated.

Although short in duration, this first phase 3 study indicates that a 6-monthly leuprolide acetate treatment represents a promising treatment to suppress pubertal hormones and progression of secondary signs of sexual maturation. Such a convenient administration might improve feasibility and adherence.

Reference: 1. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR; ESPE-LWPES GnRH Analogs Consensus Conference Group, Antoniazzi F, Berenbaum S, Bourguignon JP, Chrousos GP, Coste J, Deal S, de Vries L, Foster C, Heger S, Holland J, Jahnukainen K, Juul A, Kaplowitz P, Lahlou N, Lee MM, Lee P, Merke DP, Neely EK, Oostdijk W, Phillip M, Rosenfield RL, Shulman D, Styne D, Tauber M, Wit JM. (2009) Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 123(4):e752–e762

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