Back to resultsA Study of the Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adult Men With Hypogonadotropic Hypogonadism (HH) (P07937)
Primary Purpose
Hypogonadism, Hypogonadotropic Hypogonadism
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Corifollitropin alfa
hCG
Sponsored by
About this trial
This is an interventional treatment trial for Hypogonadism
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Corifollitropin alfa 150 μg + hCG
Arm Description
During a 16-week pretreatment phase, participants will receive twice-weekly subcutaneous (SC) injections of hCG 1500 or 3000 international units (IU). Eligible participants will then be enrolled in the combined treatment phase in which they will receive a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants will continue to receive twice-weekly hCG injections on the same schedule as the pretreatment phase.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01709331
Brief Title
A Study of the Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adult Men With Hypogonadotropic Hypogonadism (HH) (P07937)
Official Title
A Phase III, Multi-center, Open Label, Uncontrolled Trial to Investigate the Efficacy and Safety of MK-8962 (Corifollitropin Alfa) in Combination With Human Chorionic Gonadotropin (hCG) in Inducing Increased Testicular Volume and Spermatogenesis in Adult Men With Hypogonadotropic Hypogonadism Who Remain Azoospermic When Treated With hCG Alone (Phase III; Protocol No. MK-8962-031-00 [Also Known as SCH 900962, P07937])
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
February 11, 2013 (Actual)
Primary Completion Date
April 8, 2015 (Actual)
Study Completion Date
April 8, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Organon and Co
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadism, Hypogonadotropic Hypogonadism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Corifollitropin alfa 150 μg + hCG
Arm Type
Experimental
Arm Description
During a 16-week pretreatment phase, participants will receive twice-weekly subcutaneous (SC) injections of hCG 1500 or 3000 international units (IU). Eligible participants will then be enrolled in the combined treatment phase in which they will receive a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants will continue to receive twice-weekly hCG injections on the same schedule as the pretreatment phase.
Intervention Type
Drug
Intervention Name(s)
Corifollitropin alfa
Other Intervention Name(s)
MK-8962
Intervention Description
Corifollitropin alfa 150 μg by SC injection, once every 2 weeks for 52 weeks
Intervention Type
Drug
Intervention Name(s)
hCG
Intervention Description
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)
Primary Outcome Measure Information:
Title
Change From Baseline in Log-Transformed Testicular Volume at Week 52
Description
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
Title
Percentage of Participants With Anti-Corifollitropin Alfa Antibodies
Description
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
Secondary Outcome Measure Information:
Title
Percentage of Participants With Induced Spermatogenesis Resulting in a Sperm Count ≥1x10^6/mL at or Before Week 52
Description
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
28270212
Citation
Nieschlag E, Bouloux PG, Stegmann BJ, Shankar RR, Guan Y, Tzontcheva A, McCrary Sisk C, Behre HM. 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 Mar 7;15(1):17. doi: 10.1186/s12958-017-0232-y.
Results Reference
result
Learn more about this trial
A Study of the Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adult Men With Hypogonadotropic Hypogonadism (HH) (P07937)
We'll reach out to this number within 24 hrs