title: An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism.
abstract: 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 μg corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting 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 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 × 106/mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated.
  
  
  CONCLUSIONS
  Corifollitropin alfa 150 μg 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.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01709331 .
authors.affiliation: University Hospital of Muenster, Center of Reproductive Medicine and Andrology, Domagkstraße 11, D-48149, Muenster, Germany. eberhard.nieschlag@ukmuenster.de.
authors.forename: Eberhard
authors.identifier: http://orcid.org/0000-0002-1403-3298
authors.initials: E
authors.lastname: Nieschlag
authors.affiliation: The Royal Free Hospital, Pond St, London, NW3 2QG, UK.
authors.forename: Pierre-Marc G
authors.initials: PG
authors.lastname: Bouloux
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Stegmann
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: R Ravi
authors.initials: RR
authors.lastname: Shankar
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Anjela
authors.initials: A
authors.lastname: Tzontcheva
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: McCrary Sisk
authors.affiliation: University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, D-06120, Halle, Germany.
authors.forename: Hermann M
authors.initials: HM
authors.lastname: Behre
mesh_terms: D000328:Adult; D053713:Azoospermia / Q000150:complications / Q000188:drug therapy*; D006063:Chorionic Gonadotropin / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D043373:Follicle Stimulating Hormone, Human / Q000627:therapeutic use*; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006063:Chorionic Gonadotropin; D043373:Follicle Stimulating Hormone, Human; C437186:follicle stimulating hormone, human, with HCG C-terminal peptide
keywords: Corifollitropin alfa; Gonadotropin deficiency; Hypogonadotropic hypogonadism; Male infertility; Testis