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Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adolescent Males With Hypogonadotropic Hypogonadism (HH)

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ClinicalTrials.gov Identifier: NCT03019575
Recruitment Status : Recruiting
First Posted : January 12, 2017
Last Update Posted : September 13, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
The purpose of the study is to investigate whether corifollitropin alfa (MK-8962), administered in combination with human chorionic gonadotropin (hCG), increases the testicular volume in adolescent males aged 14 to <18. In addition, the study will evaluate participants for the development of corifollitropin alfa antibodies over the course of 64 weeks of treatment.

Condition or disease Intervention/treatment Phase
Hypogonadotropic Hypogonadism Drug: Corifollitropin alfa Drug: hCG Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Multi-Center, Open Label, Single-Group Trial to Investigate the Efficacy and Safety of MK-8962 (Corifollitropin Alfa) in Combination With Human Chorionic Gonadotropin (hCG) for Initiation or Restoration of Puberty as Assessed by Increased Testicular Volume in Adolescent Males 14 to <18 Years Old With Hypogonadotropic Hypogonadism (Phase III; Protocol No. MK-8962-043-00)
Actual Study Start Date : February 2, 2017
Estimated Primary Completion Date : May 25, 2020
Estimated Study Completion Date : May 25, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Corifollitropin alfa + hCG Drug: Corifollitropin alfa
Corifollitropin alfa 100 μg (body weight ≤60 kg) or 150 μg (body weight >60 kg) by SC injection, once every 2 weeks for 64 weeks (Day 1/Week 0 through Week 64).
Other Name: MK-8962

Drug: hCG
hCG 500-5000 IU by SC injection; first dose will be administered on the last day of Week 12 (Day 85), and treatment will continue, twice a week, from Week 13 through Week 64.




Primary Outcome Measures :
  1. Log-Transformed Testicular Volume at Week 64 [ Time Frame: Baseline and Week 64 ]
    Percentage change from baseline in Log-Transformed Testicular Volume at Week 64

  2. Adverse Events [ Time Frame: Up to Week 65 ]
    Percentage of participants with adverse events

  3. Anti-Corifollitropin Alfa Antibodies [ Time Frame: Up to Week 65 ]
    Percentage of participants with anti-corifollitropin alfa antibodies


Secondary Outcome Measures :
  1. Serum Inhibin B Concentrations at Week 64 [ Time Frame: Baseline and Week 64 ]
    Change from baseline in serum inhibin B concentrations at Week 64

  2. Growth Velocity at Week 36 and Week 64 [ Time Frame: Baseline, Week 36, and Week 64 ]
    Growth Velocity will be extracted using the slopes estimated from an overall mixed random intercept and random slope model of height (cm) and time (in years) and age as covariates.

  3. Tanner Stage of Pubertal Development at Week 12, Week 36, and Week 64 [ Time Frame: Baseline, Week 12, Week 36, and Week 64 ]
    Tanner Staging will be recorded for both pubic hair and testicular volume.

  4. Area-Under-The-Curve at Steady State (AUC_ss) of Corifollitropin Alfa [ Time Frame: Pre-initial-dose up to 64 weeks ]
    AUC_ss of corifollitropin alfa through 64 weeks of treatment

  5. Maximum Concentration at Steady State (Cmax_ss) of Corifollitropin Alfa [ Time Frame: Pre-initial-dose up to 64 weeks ]
    Cmax_ss of corifollitropin alfa through 64 weeks of treatment

  6. Minimum Concentration at Steady State (Cmin_ss) of Corifollitropin Alfa [ Time Frame: Pre-initial-dose up to 64 weeks ]
    Cmin_ss of corifollitropin alfa through 64 weeks of treatment

  7. Total Body Clearance (CL) of Corifollitropin Alfa [ Time Frame: Pre-initial-dose up to 64 weeks ]
    CL of corifollitropin alfa through 64 weeks of treatment

  8. Volume of Distribution (V) of Corifollitropin Alfa [ Time Frame: Pre-initial-dose up to 64 weeks ]
    V of corifollitropin Alfa through 64 weeks of treatment

  9. Testicular Echogenicity at Baseline, Week 12, Week 36, and Week 64 [ Time Frame: Baseline, Week 12, Week 36, and Week 64 ]
    Assessment of testicular echogenicity at baseline and weeks 12, 36, and 64. Any changes over time will be described.

  10. Luteinizing Hormone (LH) at Baseline, Week 12, Week 36, and Week 64 [ Time Frame: Baseline, Week 12, Week 36, and Week 64 ]
    Change from baseline in LH at weeks 12, 36, and 64

  11. Calculated Free Testosterone (T) at Baseline, Week 12, Week 36, and Week 64 [ Time Frame: Baseline, Week 12, Week 36, and Week 64 ]
    Change from baseline in calculated free T at weeks 12, 36, and 64

  12. Total Testosterone (Total T) at Baseline, Week 12, Week 36, and Week 64 [ Time Frame: Baseline, Week 12, Week 36, and Week 64 ]
    Change from baseline in Total T at weeks 12, 36, and 64

  13. Estradiol (E2) at Baseline, Week 12, Week 36, and Week 64 [ Time Frame: Baseline, Week 12, Week 36, and Week 64 ]
    Change from baseline in E2 at weeks 12, 36, and 64

  14. Sex Hormone-Binding Globulin (SHBG) at Baseline, Week 12, Week 36, and Week 64 [ Time Frame: Baseline, Week 12, Week 36, and Week 64 ]
    Change from baseline in SHBG at weeks 12, 36, and 64

  15. Anti-Müllerian Hormone (AMH) at Baseline, Week 12, Week 36, and Week 64 [ Time Frame: Baseline, Week 12, Week 36, and Week 64 ]
    Change from baseline in AMH at weeks 12, 36, and 64



Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years to 17 Years   (Child)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   All participants must be male.
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have legal representative who understands the study procedures, alternative treatments available and risks involved with the study, and voluntarily agrees to the individual's participation by giving written informed consent, and the individual has an age-appropriate understanding of the same to give informed written assent if applicable.
  • Diagnosed with hypogonadotropic hypogonadism (either isolated or associated with panhypopituitarism), either congenital or acquired with onset prior to puberty.
  • Have bilateral pre-gonadarche testes as defined by testicular volume <4.0 mL for each testicle, as determined by ultrasound and assessed by the investigator (if qualified) or local radiologist with appropriate training and expertise in reading testicular ultrasound. Note: participants with a volume of <4.0 mL in one testicle and a volume of 4-8 mL in the other testicle are considered to be pre-gonadarche and may participate, if there is no history or evidence of a primary testicular disorder (see Exclusion Criteria 1 and 2).
  • Circulating levels of total testosterone (Total T) less than the lower limit of normal (LLN) of 8.3 nmol/L as specified by the central lab for a young healthy adult male.
  • Follicle stimulating hormone (FSH) ≤2 IU/L and luteinizing hormone (LH) ≤2 IU/L.
  • Inhibin-B levels ≤35 pg/mL. (Note: if individual has inhibin-B levels >35 pg/mL, but meets all of the other inclusion/exclusion criteria, either a GnRH agonist (GnRHa) stimulation test or GnRH IV infusion test may be performed.
  • In good general physical and mental health, in the opinion of the investigator/sponsor, as assessed by physical examination and routine clinical laboratory tests.
  • Have a parent/guardian able and willing to support the individual's participation by supporting adherence to study drug dosing and visit schedules.

Exclusion Criteria:

  • History of bilateral cryptorchidism (maldescended testes) or unilateral cryptorchidism treated after the age of 2 years.
  • History or presence of clinically significant testicular problems (e.g., epididymitis, orchitis, testicular torsion, varicocele Grade III, testicular atrophy, occlusive azoospermia, etc.) that would impair participants response to treatment or has had known damage or injury to the vas deferens.
  • Previous treatment with GnRH, gonadotropins (e.g., hCG, FSH) or androgens (e.g., testosterone, etc.). Note: Use of GnRH and gonadotropins for diagnostic testing purposes only is allowed. Participants with use of hCG and androgen therapy prior to the age of 2 years old can be included in the trial. Participants with transient use of androgens (i.e., for less than 2 weeks) that was stopped at least 6 months prior to signing informed consent can also be included in the trial.
  • Untreated or inadequately treated pituitary or hypothalamic tumor.
  • Uncontrolled endocrinopathies, including thyroid, adrenal, and pituitary disorders not on stable replacement therapies.
  • History of active pituitary hypersecretion as evidenced by hyperprolactinemia or Cushing's disease, acromegaly, or any other active pituitary hypersecretion syndrome. (Note: Individuals who have been treated and are clinically stable, with no evidence of hypersecretion for at least 12 months prior to screening, may participate.
  • Has had hypophysectomy within 12 months to the start of screening.
  • History of oncologic chemotherapy treatment.
  • Brain radiotherapy within 12 months of start of treatment for a primary tumor, or any history of brain radiotherapy for metastatic disease.
  • Diabetes mellitus.
  • History of Human Immunodeficiency Virus (HIV).
  • Has renal insufficiency, as determined by investigator, based on serum creatinine, blood urea nitrogen, and estimated glomerular filtration rate.
  • Clinically significant liver disease, including active viral hepatitis or cirrhosis. Individuals with a prior history of liver disease which is now inactive or successfully treated may be enrolled if all liver function values performed within the past year have been normal and within the normal range at Visit 1.
  • Recent history of recreational or illicit drug use, including marijuana; or routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking.
  • Has an allergy/sensitivity to gonadotropins or its/their excipients.
  • Has used an investigational drug and/or participated in any other clinical trial within the past 8 weeks (prior to Visit 2), or will participate in any other clinical trials (excluding surveys) during the course of this trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03019575


Contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Brazil
Centro de Diabetes Curitiba ( Site 0012) Recruiting
Curitiba, Brazil, 80810-040
Contact: Study Coordinator    +554130231252      
Hospital de Clinicas de Porto Alegre ( Site 0014) Recruiting
Porto Alegre, Brazil, 90035-903
Contact: Study Coordinator    +555133596368      
Hosp das Clinicas da Faculdade de Medicina da Univ de Sao Paulo ( Site 0015) Recruiting
Sao Paulo, Brazil, 05403-000
Contact: Study Coordinator    +551126618833      
Denmark
Rigshospitalet, University department of Growth and Reproduction ( Site 0051) Recruiting
Copenhagen, Denmark, 2100
Contact: Study Coordinator    +4535455085      
Italy
AOU Careggi ( Site 0042) Recruiting
Firenze, Italy, 50139
Contact: Study Coordinator    +390554271415      
Policlinico Umberto I ( Site 0043) Recruiting
Roma, Italy, 00161
Contact: Study Coordinator    +390649970540      
IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0044) Recruiting
Roma, Italy, 00165
Contact: Study Coordinator    +390668592605      
Mexico
Instituto Nacional de Pediatria ( Site 0007) Recruiting
Mexico City, Mexico, 04530
Contact: Study Coordinator    +52108409001330      
Hospital Infantil de Mexico Federico Gomez ( Site 0006) Recruiting
Mexico City, Mexico, 06720
Contact: Study Coordinator    +5215516562649      
Russian Federation
Kazan State Medical University ( Site 0024) Active, not recruiting
Kazan, Russian Federation, 420048
Federal State Budget Institution Endocrinological Research Center ( Site 0021) Completed
Moscow, Russian Federation, 117036
City children polyclinic #44 ( Site 0025) Active, not recruiting
Saint Petersburg, Russian Federation, 191144
St.Petersburg State Pediatric Medical University ( Site 0023) Active, not recruiting
Saint Petersburg, Russian Federation, 194100
Republic Children Clinical Hospital ( Site 0022) Active, not recruiting
Ufa, Russian Federation, 450106
South Africa
Little Company of Mary Hospital ( Site 0017) Recruiting
Pretoria, South Africa, 0181
Contact: Study Coordinator    +27124607900      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03019575     History of Changes
Other Study ID Numbers: 8962-043
2015-001878-18 ( EudraCT Number )
First Posted: January 12, 2017    Key Record Dates
Last Update Posted: September 13, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

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