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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01709331
First received: October 16, 2012
Last updated: June 8, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Hypogonadism
Hypogonadotropic Hypogonadism
Drug: Corifollitropin alfa
Drug: hCG
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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])

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change From Baseline in Log-Transformed Testicular Volume at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Week 57 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    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.


Enrollment: 18
Study Start Date: February 2013
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Corifollitropin alfa 150 μg + hCG
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.
Drug: Corifollitropin alfa
Corifollitropin alfa 150 μg by SC injection, once every 2 weeks for 52 weeks
Other Name: MK-8962
Drug: hCG
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)

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01709331

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01709331     History of Changes
Other Study ID Numbers: P07937  2012-001258-25  MK-8962-031 
Study First Received: October 16, 2012
Results First Received: April 4, 2016
Last Updated: June 8, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Hypogonadism
Gonadal Disorders
Endocrine System Diseases
Chorionic Gonadotropin
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2016