An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism

作者：Nieschlag Eberhard^*; Bouloux Pierre Marc G; Stegmann Barbara J; Shankar R Ravi; Guan Yanfen; Tzontcheva Anjela; Sisk Christine McCrary; Behre Hermann M

来源：Reproductive Biology and Endocrinology, 2017, 15(1): 1-9.

DOI：10.1186/s12958-017-0232-y

• Corifollitropin alfa
• Gonadotropin deficiency
• Hypogonadotropic hypogonadism
• Male infertility
• Testis

Background: Hypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of corifollitropin alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH.
Methods: This was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 mu g corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count >= 1 Chi 10(6)/mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-corifollitropin alfa antibodies and the occurrence of adverse events (AEs).
Results: Mean (+/- SD) testicular volume increased from 8.6 (+/- 6.09) mL to 17.8 (+/- 8.93) mL ( geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count >= 1 Chi 10(6)/mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated.
Conclusions: Corifollitropin alfa 150 mu g administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone.

• 出版日期2017-3-7