Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adolescent Males With Hypogonadotropic Hypogonadism (HH) (MK-8962-043)
Condition: Hypogonadotropic Hypogonadism
MeSH terms: Hypogonadism
Intervention: Corifollitropin alfa; hCG
Intervention description: CFA administered 100 μg (if body weight ≤60 kg) or 150 μg (if body weight >60 kg) by SC injection, once every 2 weeks for 64 weeks (Day 1, Week 0 through Week 64).; hCG 500-5000 IU reconstituted with 1 ml of 0.9% sodium chloride solution, as a SC injection twice a week for 52 weeks (last day of Week 12 through Week 64).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: Male
Minimum age: 14 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to investigate whether corifollitropin alfa (MK-8962),
      administered alone for 12 weeks and then in combination with human chorionic gonadotropin
      (hCG) for 52 weeks, increases the testicular volume in adolescent males aged 14 to <18. In
      addition, the study will evaluate participants for safety, tolerability and for the
      development of corifollitropin alfa antibodies. No formal hypothesis will be tested for this
      estimation study
    

Eligibility 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).

          -  Have 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.

          -  Have follicle stimulating hormone (FSH) ≤2 IU/L and luteinizing hormone (LH) ≤2 IU/L.

          -  Have 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:

          -  Have a history of bilateral cryptorchidism (maldescended testes) or unilateral
             cryptorchidism treated after the age of 2 years.

          -  Have a 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.

          -  Had any 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.

          -  Has an untreated or inadequately treated pituitary or hypothalamic tumor.

          -  Have uncontrolled endocrinopathies, including thyroid, adrenal, and pituitary
             disorders not on stable replacement therapies.

          -  Has a 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.

          -  Has history of oncologic chemotherapy treatment.

          -  Has had brain radiotherapy within 12 months of start of treatment for a primary tumor,
             or any history of brain radiotherapy for metastatic disease.

          -  Has diabetes mellitus.

          -  Has 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.

          -  Has 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.

          -  Has had a 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.