Hypogonadism, Hypogonadotropic Hypogonadism
Conditions
Brief summary
This study will assess if corifollitropin alfa (MK-8962), when administered in combination with human chorionic gonadotropin (hCG), will increase testicular volume in men with HH who remain azoospermic after treatment with hCG alone. Hypothesis: The lower limit of the 95% confidence interval for the geometric mean increase in testicular volume from Day 1 to Week 52 is greater than one.
Interventions
DRUGCorifollitropin alfa
Corifollitropin alfa 150 μg by SC injection, once every 2 weeks for 52 weeks
DRUGhCG
hCG 1500 or 3000 IU by SC injection twice a week; administered alone for 16 weeks (pre-treatment phase) and then in combination with corifollitropin alfa for 52 weeks (combined treatment phase)
Sponsors
Organon and Co
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with hypogonadotropic hypogonadism, either congenital or acquired * Have low circulating levels of testosterone * Have low circulating levels of gonadotropins (follicle stimulating hormone \[FSH\]; luteinizing hormone) * Presence of both scrotal testes * Have azoospermia (no measurable level of sperm) * Adequate replacement of other pituitary hormones * Good general physical and mental health
Exclusion criteria
* Primary hypogonadism, such as Klinefelter's syndrome * History of unilateral or bilateral cryptorchidism (maldescended testes) * History or presence of testicular pathology of clinical importance (e.g., epididymitis, orchitis, testicular torsion, varicocele stage III, testicular atrophy, occlusive azoospermia, etc), and/or vasectomy * Treated with FSH, hCG or gonadotropin-releasing hormone (GnRH) within previous 3 months or for more than 1 month within previous 6 months * Proven spermatogenesis with hCG treatment alone * Previous unsuccessful attempt with hCG in combination with human menopausal gonadotropin (hMG)/FSH to achieve spermatogenesis * Required a dose of hCG of more than 6000 international units (IU) per week in a previous attempt to normalize T levels * Untreated pituitary or hypothalamic tumor, or inadequately treated pituitary or hypothalamic tumor that is likely to progress during the study * History or presence (known or suspected) of testicular, prostatic or breast cancer * Prostate pathology of clinical importance * Past or present oncologic treatment (chemo/radiotherapy) * Diabetes mellitus * Clinically significant, untreated hyperprolactinaemia * Uncontrolled non-gonadal endocrinopathies (thyroid, adrenal, pituitary disorders) * Tested positive for Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C * User of recreational or illicit drugs or has had a recent history (within the past year) of drug abuse or dependence, or increased alcohol consumption * Allergy/sensitivity to gonadotropins or its/their excipients * Has received within previous 1 month or plans to use: Hormonal preparations other than the study medication, drugs that are known to impair testicular function, agents known to affect sex hormone secretion and/or drugs that are known or suspected to be teratogenic * Used any investigational drugs within three months or actively participating in another study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Log-Transformed Testicular Volume at Week 52 | Baseline and Week 52 | Participants underwent testicular ultrasound in the pretreatment phase at Weeks -16, -8, -1; and during the combined treatment phase at Baseline (predose, Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. The testicular volume was measured as the sum of volumes of left and right testes. The mean change from Day 1 in log-transformed testicular volume was analyzed using a mixed model with a fixed effect for time point and a random effect for the participant. For each time point, the mean change from Day 1 to that time point and the associated 95% confidence interval (CI) was calculated. The geometric mean fold change in testicular volume and its 95% CI was obtained by exponentiation. |
| Percentage of Participants With Anti-Corifollitropin Alfa Antibodies | Up to Week 57 | Blood samples were collected for assessment of anti-corifollitropin alfa antibodies in the pretreatment phase at Week -16 and Week -1; during the combined treatment phase at Weeks 4, 16, 28, 50, 52; and at the post-treatment follow-up visit, which could occur from Week 53 up to Week 57. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Induced Spermatogenesis Resulting in a Sperm Count ≥1x10^6/mL at or Before Week 52 | Up to Week 52 | Semen samples were produced by masturbation after at least 48 hours of sexual abstinence and collected for evaluation in the pretreatment phase at Week -1, and during the combined treatment phase at Weeks 16, 28, 40, and 52. |
Participant flow
Pre-assignment details
Twenty-three participants entered the 16-week pretreatment phase with hCG. At the end of the pretreatment phase, 18 participants were enrolled in the 52-week combined treatment phase.
Participants by arm
| Arm | Count |
|---|---|
| Corifollitropin Alfa 150 μg + hCG During a 16-week pretreatment phase, participants received twice-weekly SC injections of hCG 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Corifollitropin Alfa 150 μg + hCG |
|---|---|
| Age, Continuous | 31.5 Years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
Change From Baseline in Log-Transformed Testicular Volume at Week 52
Participants underwent testicular ultrasound in the pretreatment phase at Weeks -16, -8, -1; and during the combined treatment phase at Baseline (predose, Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. The testicular volume was measured as the sum of volumes of left and right testes. The mean change from Day 1 in log-transformed testicular volume was analyzed using a mixed model with a fixed effect for time point and a random effect for the participant. For each time point, the mean change from Day 1 to that time point and the associated 95% confidence interval (CI) was calculated. The geometric mean fold change in testicular volume and its 95% CI was obtained by exponentiation.
Time frame: Baseline and Week 52
Population: Full Analysis Set (FAS) population, which consisted of all participants who received any dose of corifollitropin alfa and who had a baseline and at least one post-baseline measurement of testicular volume.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Corifollitropin Alfa 150 μg + hCG | Change From Baseline in Log-Transformed Testicular Volume at Week 52 | 2.3 Fold change |
Primary
Percentage of Participants With Anti-Corifollitropin Alfa Antibodies
Blood samples were collected for assessment of anti-corifollitropin alfa antibodies in the pretreatment phase at Week -16 and Week -1; during the combined treatment phase at Weeks 4, 16, 28, 50, 52; and at the post-treatment follow-up visit, which could occur from Week 53 up to Week 57.
Time frame: Up to Week 57
Population: All-Subjects-as-Treated (ASaT) population, which consisted of all participants who received any dose of corifollitropin alfa.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa 150 μg + hCG | Percentage of Participants With Anti-Corifollitropin Alfa Antibodies | 0 Percentage of participants |
Secondary
Percentage of Participants With Induced Spermatogenesis Resulting in a Sperm Count ≥1x10^6/mL at or Before Week 52
Semen samples were produced by masturbation after at least 48 hours of sexual abstinence and collected for evaluation in the pretreatment phase at Week -1, and during the combined treatment phase at Weeks 16, 28, 40, and 52.
Time frame: Up to Week 52
Population: FAS population, which consisted of all participants who received any dose of corifollitropin alfa and who had a baseline and at least one post-baseline measurement of testicular volume.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa 150 μg + hCG | Percentage of Participants With Induced Spermatogenesis Resulting in a Sperm Count ≥1x10^6/mL at or Before Week 52 | 77.8 Percentage of participants |