[OA] Nieschlag E, Bouloux PG, Stegmann BJ, et al. An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism. Reprod Biol Endocrinol 2017;15(1):17. http://rbej.biomedcentral.com/articles/10.1186/s12958-017-0232-y
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 mug corifollitropin alfa every other week.
The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count >/=1 x 106/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 x 106/mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated.
CONCLUSIONS: Corifollitropin alfa 150 mug 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.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT01709331 .
The trial began at Week -16 with an hCG-only pretreatment phase, during which eligible men with HH were treated with 1500 IU of hCG (Merck & Co., Inc., Kenilworth, NJ, USA) administered subcutaneously (SC) twice-weekly for 16 weeks to normalize T levels and to determine if hCG alone would be sufficient to achieve spermatogenesis.
The dose could be increased to 3000 IU twice-weekly after 8 weeks if the Total T level remained below the unequivocal lower limits of the normal range (8.68 nmol/L [250 ng/dL]).
Continuation into the 52-week combined treatment phase (corifollitropin alfa with hCG) was limited to subjects with normalized T levels who remained azoospermic at the conclusion of the pretreatment phase.
Day 1 of the trial was the first day of the 52-week combined treatment phase (corifollitropin alfa with hCG).
During this phase, subjects received corifollitropin alfa (150 μg SC) once every two weeks in addition to twice-weekly hCG.
The initial hCG dose in the combined treatment phase was the same as the final dose in the pretreatment phase; the dose was then adjusted up to 3000 IU or down to 1500 IU as needed to maintain Total T and estradiol (E2) levels within acceptable ranges according to the investigator’s discretion.
hCG was administered on the same two days every week (Monday/Thursday or Tuesday/Friday), and corifollitropin alfa was given on one of the days when hCG was administered. The final follow-up visit occurred at least 21 days after the last dose of corifollitropin alfa and at least seven days after the last dose of hCG.
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 mug corifollitropin alfa every other week.
The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count >/=1 x 106/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 x 106/mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated.
CONCLUSIONS: Corifollitropin alfa 150 mug 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.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT01709331 .
The trial began at Week -16 with an hCG-only pretreatment phase, during which eligible men with HH were treated with 1500 IU of hCG (Merck & Co., Inc., Kenilworth, NJ, USA) administered subcutaneously (SC) twice-weekly for 16 weeks to normalize T levels and to determine if hCG alone would be sufficient to achieve spermatogenesis.
The dose could be increased to 3000 IU twice-weekly after 8 weeks if the Total T level remained below the unequivocal lower limits of the normal range (8.68 nmol/L [250 ng/dL]).
Continuation into the 52-week combined treatment phase (corifollitropin alfa with hCG) was limited to subjects with normalized T levels who remained azoospermic at the conclusion of the pretreatment phase.
Day 1 of the trial was the first day of the 52-week combined treatment phase (corifollitropin alfa with hCG).
During this phase, subjects received corifollitropin alfa (150 μg SC) once every two weeks in addition to twice-weekly hCG.
The initial hCG dose in the combined treatment phase was the same as the final dose in the pretreatment phase; the dose was then adjusted up to 3000 IU or down to 1500 IU as needed to maintain Total T and estradiol (E2) levels within acceptable ranges according to the investigator’s discretion.
hCG was administered on the same two days every week (Monday/Thursday or Tuesday/Friday), and corifollitropin alfa was given on one of the days when hCG was administered. The final follow-up visit occurred at least 21 days after the last dose of corifollitropin alfa and at least seven days after the last dose of hCG.
