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 (MK-8962-043)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 15
- 主要终点
- Number of Participants Who Experienced an Adverse Event (AE)
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 17 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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.
研究组 & 干预措施
Corifollitropin alfa (CFA)+human Chorionic Gonadotropin (hCG)
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.
干预措施: Corifollitropin alfa (Drug)
Corifollitropin alfa (CFA)+human Chorionic Gonadotropin (hCG)
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.
干预措施: hCG (Drug)
结局指标
主要结局
Number of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to approximately 71 Weeks
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.
Percentage of Participants With Anti-Corifollitropin Alfa (CFA) Antibodies
时间窗: Up to approximately 71 Weeks
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.
Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to approximately 64 Weeks
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 discontinued study treatment due to an AE was reported.
Change From Baseline in Log-Transformed Testicular Volume (TV) to Week 64
时间窗: Baseline and 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.
次要结局
- Change From Baseline in Serum Inhibin B Concentration to Week 64(Baseline and Week 64)
- Change From Baseline in Luteinizing Hormone (LH) to Week 12, Week 36, and Week 64(Baseline, Week 12, Week 36, and Week 64)
- Change From Baseline in Tanner Stage (TS) of Pubertal Development for Pubic Hair to Week 12, Week 36, and Week 64(Baseline, Week 12, Week 36, and Week 64)
- Change From Baseline in Testicular Echogenicity to Week 12, Week 36, and Week 64(Baseline, Week 12, Week 36, and Week 64)
- Change From Baseline in Total Testosterone (Total T) to Week 12, Week 36, and Week 64(Baseline, Week 12, Week 36, and Week 64)
- Growth Velocity at Week 36(Week 36)
- Change From Baseline in TS of Pubertal Development for Genital Growth to Week 12, Week 36, and Week 64(Baseline, Week 12, Week 36, and Week 64)
- Change From Baseline in Estradiol (E2) to Week 12, Week 36, and Week 64(Baseline, Week 12, Week 36, and Week 64)
- Change From Baseline in Anti-Müllerian Hormone (AMH) to Week 12, Week 36, and Week 64(Baseline, Week 12, Week 36, and Week 64)
- Growth Velocity at Week 64(Week 64)
- Change From Baseline in Calculated Free Testosterone (T) to Week 12, Week 36, and Week 64(Baseline, Week 12, Week 36, and Week 64)
- Mean Serum Concentration of CFA(Day 1: predose, 6-24 hours postdose; Day 3: 32-52 hours postdose; Day 5: 72-120 hours postdose; Day 8: 144-192 hours postdose; Day 11: 216-244 hours postdose; Days 29, 85, 169, 253, 337: predose; Days 449, 456: postdose)
- Change From Baseline in Sex Hormone-Binding Globulin (SHBG) to Week 12, Week 36, and Week 64(Baseline, Week 12, Week 36, and Week 64)