Hypogonadotropic hypogonadism (HH) in males may result from either absent or inadequate gonadotropin-releasing hormone (GnRH) secretion by the hypothalamus or failure of pituitary gonadotropin secretion (luteinizing hormone (LH) & follicle stimulating hormone (FSH)). HH is characterized by androgen deficiency and by inappropriately low serum concentrations of LH and FSH. MedDRA version: 16.1 Level: LLT Classification code 10021012 Term: Hypogonadotrophic hypogonadism System Organ Class: 100000
Conditions
Interventions
Trade Name: ELONVA
Product Name: corifollitropin alfa
Product Code: MK-8962, SCH 900962
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: corifollitropin alfa
CAS
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Each subject must be a male, diagnosed with hypogonadotropic hypogonadism (either congenital or acquired), and be =18 to =50 years of age at the time of signing ICF. (Note: Subjects with drug-induced HH [e.g. misuse of anabolic steroids, chronic use of glucocorticoids or narcotic analgesics, etc.] are not allowed to participate). Each subject must have low circulating levels of Testosterone (T): T = 6 nmol/L, and low circulating levels of gonadotropins (FSH = 2 IU/L and LH = 2 IU/L), as assessed after an adequate wash-out period from previous testosterone use (if applicable). Each subject must have presence of scrotal testes (left and right) and must have azoospermia (according to the criteria specified in the 2010 World Health Organization [WHO] Laboratory Manual for the Examination and Processing of Human Semen, 5th Edition). Each subject must have adequate replacement of other pituitary hormones (if applicable). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: The subject has primary hypogonadism such as Klinefelter's syndrome, or has a history of unilateral or bilateral cryptorchidism (maldescended testes). (Note: Subjects with a history of unilateral cryptorchidism which was treated before the age of 2 years are allowed in this trial). The subject has testicular pathology of clinical importance (e.g., epididymitis, orchitis, testicular torsion, varicocele stage III, testicular atrophy, occlusive azoospermia, etc). The subject has been treated with FSH, hCG or gonadotropin releasing hormone (GnRH) within a period of three months prior to signing informed consent or for more than one month within a period of six months prior to signing informed consent. The subject has proven spermatogenesis upon hCG treatment alone, or has had a previous unsuccessful attempt with hCG in combination with human menopausal gonadotropin (hMG)/FSH to achieve spermatogenesis. The subject had required a dose of hCG of more than 6000 IU per week in a previous attempt to normalize T levels. The subject has untreated pituitary or hypothalamic tumor, or inadequately treated pituitary or hypothalamic tumor that is likely to progress during the study. The subject has had hypophysectomy within a period of 6 months prior to the start of screening. The subject has a history or presence (known or suspected) of testicular, prostatic or breast cancer, has prostate pathology of clinical importance, or has past or present oncological treatment (chemo/radiotherapy). (Note: Previous local radiation of the brain in case of a pituitary tumor is allowed, but not in case of brain metastases). The subject has diabetes mellitus, untreated hyperprolactinaemia or uncontrolled non-gonadal endocrinopathies (thyroid, adrenal, pituitary disorders). The subject has tested positive for Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C (results obtained within 1 year prior to signing ICF are considered valid).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of the trial are: 1) to assess the efficacy of 150 µg MK-8962, given once every two weeks for 52 weeks - in combination with a twice weekly dose of hCG - to increase testicular volume measured as the sum of volumes of left and right testes by ultrasound in men with hypogonadotropic hypogonadism who remain azoospermic after 16 weeks of hCG alone and 2) to evaluate whether treatment with 150 µg MK-8962 for 52 weeks in combination with hCG is safe in HH men, as evaluated by the occurrence of (serious) adverse events and presence of anti-MK-8962 antibodies (pre-specified safety endpoint).;Secondary Objective: The key secondary objectives are 1) to assess the efficacy of 150 µg MK-8962, given once every two weeks for 52 weeks - in combination with a twice weekly dose of hCG - to induce spermatogenesis resulting in a sperm count = 1x106 / mL in HH men who remain azoospermic after 16 weeks of hCG alone, and 2) to characterize the pharmacokinetics of MK-8962 in HH men after subcutaneous (SC) administration of 150 µg MK-8962 based on serum MK-8962 concentrations. Other secondary objectives are to evaluate the effect of 150 µg MK-8962 in combination with hCG on endocrinological parameters (FSH, LH, hCG, total testosterone [total T], estradiol [E2], sex hormone-binding globulin [SHBG], inhibin-B, and anti-Müllerian hormone [AMH]) as determined by a central laboratory and on sperm parameters (concentration, morphology, motility) as determined by the local laboratory of each clinic. ;Primary end point(s): The primary efficacy endpoint for the current trial is the change from baseline from Day 1 (i.e., the first day of combined treatment with MK-8962 and hCG) to Week 52 in log-transformed testicular volume (measured as the sum of volumes of left and right testes by ultrasound).;Timepoint(s) of evaluation of this end point: Wk -16, Wk -8, Wk -1, Day 1 and every 4 weeks thereafter till Wk 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Induced spermatogenesis (i.e., sperm count = 1x106 / mL). • characterization of MK-8962 pharmacokinetics in HH men based on MK-8962 serum concentration data. • Sperm concentration • Sperm morphology • Sperm motility • Serum hormone levels (FSH, LH, hCG, total testosterone, E2, SHBG, inhibin-B, and AMH). ;Timepoint(s) of evaluation of this end point: • Sperm parameters: Wk -16, Wk -1, Wk 16, Wk 28, Wk 40 and Wk 52/discontinuation visit • PK of MK-8962: detailed PK sampling during the first 2 weeks of treatment (6 visits), Wk 4, Wk 16, Wk 28, Wk 40, Wk 52/ discontinuation visit, and post-treatment follow-up visit. • Serum hormone levels: Wk-16, Wk-8, Wk-1, every 4 weeks thereafter till Wk52, and post-treatment follow-up visit. | — |
Countries
Australia, Finland, Germany, Italy, Poland, Spain, United Kingdom
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed