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)

Phase 3CompletedNCT03019575

Organon and Co17 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hypogonadotropic Hypogonadism

Interventions

Corifollitropin alfa

Eligibility

Sex: MALEMin age: 14 YearsMax age: 17 Years

Medical Language ↔ Plain English

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.

Locations (15)

Centro de Diabetes Curitiba ( Site 0012)

Curitiba, Brazil

Hospital de Clinicas de Porto Alegre ( Site 0014)

Porto Alegre, Brazil

Hosp das Clinicas da Faculdade de Medicina da Univ de Sao Paulo ( Site 0015)

São Paulo, Brazil

Rigshospitalet, University department of Growth and Reproduction ( Site 0051)

Copenhagen, Denmark

AOU Careggi ( Site 0042)

Florence, Italy

Policlinico Umberto I ( Site 0043)

Roma, Italy

IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0044)

Roma, Italy

Instituto Nacional de Pediatria ( Site 0007)

Mexico City, Mexico

Hospital Infantil de Mexico Federico Gomez ( Site 0006)

Mexico City, Mexico

Kazan State Medical University ( Site 0024)

Kazan', Russia

...and 5 more locations

Outcomes

Primary Outcomes

Change From Baseline in Log-Transformed Testicular Volume (TV) to Week 64

Participants underwent testicular ultrasound of left and right testes at pre-specified time points to measure TV. TV was measured as the sum of volumes of left and right testes. The linear mixed model with a fixed effect for baseline and Week 64 and a random effect for participant was used to calculate the mean change in log-transformed TV and associated 95% confidence intervals (CIs) from baseline to Week 64. The geometric mean ratio and its 95% CIs for TV were obtained by exponentiation. The ratio \> 1 indicated an increase in TV from baseline.

Time frame: Baseline and Week 64

Number of Participants Who Experienced an Adverse Event (AE)

An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE was reported.

Time frame: Up to approximately 71 Weeks

Number of Participants Who Discontinued Study Treatment Due to an AE

Time frame: Up to approximately 64 Weeks

Percentage of Participants With Anti-Corifollitropin Alfa (CFA) Antibodies

Blood samples were collected at pre-specified time points to assess anti-CFA antibodies. The percentage of participants with anti-CFA antibodies after administration of CFA were reported.

Time frame: Up to approximately 71 Weeks

Secondary Outcomes

Change From Baseline in Serum Inhibin B Concentration to Week 64

Serum Inhibin B concentration is a surrogate marker for spermatogenesis in males. Blood samples were collected at baseline and Week 64 post dose to report the mean change from baseline in serum inhibin concentration to Week 64. A mean change from baseline in serum inhibin B concentration to Week 64 was reported. A positive value indicated a higher serum inhibin concentration level.

Time frame: Baseline and Week 64

Growth Velocity at Week 36

Growth velocity is the rate of change in height measurement and is a marker for pubertal progress. Height was measured using a wall-mounted calibrated stadiometer. A mixed model was used to assess the overall growth velocity slope over the 36-week treatment period using the slopes estimated from an overall mixed random intercept and random slope model of height (cm) and time (yr) and age as covariates.

Time frame: Week 36

Growth Velocity at Week 64

Growth velocity is the rate of change in height measurement and is a marker for pubertal progress. Height was measured using a wall-mounted calibrated stadiometer. A mixed model was used to assess the overall growth velocity slope over the 64-week treatment period using the slopes estimated from an overall mixed random intercept and random slope model of height (cm) and time (year) and age as covariates.

Time frame: Week 64

Change From Baseline in Tanner Stage (TS) of Pubertal Development for Pubic Hair to Week 12, Week 36, and Week 64

Male participants were assessed clinically for pubertal development using the TS for pubic hair (range: Tanner I-V). TS describes sexual maturity stages (no better or worse outcome) as: Tanner I: prepubertal state, Tanner II: small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum, Tanner III: hair becomes more coarse and curly, and begins to extend laterally, Tanner IV: adult-like hair quality, extending across pubis but sparing medial thighs and Tanner V: hair extends to medial surface of the thigh. The number of participants in each Tanner stage at baseline and categorical change from baseline in Tanner stages to Weeks 12, 36 and 64 were reported.