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)

Organon

Status and phase: Completed; Phase 3

Conditions: Hypogonadotropic Hypogonadism

Treatments: Drug: Corifollitropin alfa; Drug: hCG

Study type: Interventional

Funder types: Industry

Identifiers

NCT03019575

2015-001878-18 (EudraCT Number)

MK-8962-043 (Other Identifier)

8962-043

Details and patient eligibility

About

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

Enrollment: 17 patients

Sex: Male

Ages: 14 to 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 1 patient group

Corifollitropin alfa (CFA)+human Chorionic Gonadotropin (hCG)

Experimental group

Description:

Participants received 100 μg (if body weight was ≤60 kg) or 150 μg (if body weight was \>60 kg) of CFA as a subcutaneous (SC) injection once every 2 weeks for 64 Weeks (Day 1, Week 0 through Week 64) and 500-5000 IU of hCG 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). The total treatment duration was 64 Weeks.

Treatment:

Drug: Corifollitropin alfa

Drug: hCG