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

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 alfais 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 alfacombined with hCG to increase testicular volumeand induce spermatogenesisin men with HH. This was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfain 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 μg corifollitropin alfaevery other week. The increase in testicular volume(primary efficacy endpoint) and induction of spermatogenesisresulting in a sperm count ≥1 × 106/mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti- corifollitropin alfaantibodies and the occurrence of adverse events (AEs). Mean (±SD) testicular volumeincreased 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 × 106/mL. No subject developed confirmed anti- corifollitropin alfaantibodies during the trial. Treatment was generally well tolerated. Corifollitropin alfa150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volumesignificantly, and induced spermatogenesisin >75% of men with HH who had remained azoospermic after hCG treatment alone. ClinicalTrials.gov: NCT01709331 .