Clinical trial NCT03019575: 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)
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 (MK-8962-043)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypogonadotropic Hypogonadism
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2017-01-12
Enrollment: 17
Sex: MALE
Minimum age (years): 14
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change From Baseline in Log-Transformed Testicular Volume (TV) to Week 64
timeFrame: Baseline and Week 64
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 71 Weeks
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 64 Weeks
measure: Percentage of Participants With Anti-Corifollitropin Alfa (CFA) Antibodies
timeFrame: Up to approximately 71 Weeks
Secondary outcomes:
measure: Change From Baseline in Serum Inhibin B Concentration to Week 64
timeFrame: Baseline and Week 64
measure: Growth Velocity at Week 36
timeFrame: Week 36
measure: Growth Velocity at Week 64
timeFrame: Week 64
measure: Change From Baseline in Tanner Stage (TS) of Pubertal Development for Pubic Hair to Week 12, Week 36, and Week 64
timeFrame: Baseline, Week 12, Week 36, and Week 64
measure: Change From Baseline in TS of Pubertal Development for Genital Growth to Week 12, Week 36, and Week 64
timeFrame: Baseline, Week 12, Week 36, and Week 64
measure: Mean Serum Concentration of CFA
timeFrame: 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
measure: Change From Baseline in Testicular Echogenicity to Week 12, Week 36, and Week 64
timeFrame: Baseline, Week 12, Week 36, and Week 64
measure: Change From Baseline in Luteinizing Hormone (LH) to Week 12, Week 36, and Week 64
timeFrame: Baseline, Week 12, Week 36, and Week 64
measure: Change From Baseline in Calculated Free Testosterone (T) to Week 12, Week 36, and Week 64
timeFrame: Baseline, Week 12, Week 36, and Week 64
measure: Change From Baseline in Total Testosterone (Total T) to Week 12, Week 36, and Week 64
timeFrame: Baseline, Week 12, Week 36, and Week 64
measure: Change From Baseline in Estradiol (E2) to Week 12, Week 36, and Week 64
timeFrame: Baseline, Week 12, Week 36, and Week 64
measure: Change From Baseline in Sex Hormone-Binding Globulin (SHBG) to Week 12, Week 36, and Week 64
timeFrame: Baseline, Week 12, Week 36, and Week 64
measure: Change From Baseline in Anti-Müllerian Hormone (AMH) to Week 12, Week 36, and Week 64
timeFrame: Baseline, Week 12, Week 36, and Week 64
Other outcomes:
Locations:
city: Curitiba
country: Brazil
facility: Centro de Diabetes Curitiba ( Site 0012)
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre ( Site 0014)
city: Sao Paulo
country: Brazil
facility: Hosp das Clinicas da Faculdade de Medicina da Univ de Sao Paulo ( Site 0015)
city: Copenhagen
country: Denmark
facility: Rigshospitalet, University department of Growth and Reproduction ( Site 0051)
city: Firenze
country: Italy
facility: AOU Careggi ( Site 0042)
city: Roma
country: Italy
facility: Policlinico Umberto I ( Site 0043)
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0044)
city: Mexico City
country: Mexico
facility: Instituto Nacional de Pediatria ( Site 0007)
city: Mexico City
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez ( Site 0006)
city: Kazan
country: Russian Federation
facility: Kazan State Medical University ( Site 0024)
city: Moscow
country: Russian Federation
facility: Federal State Budget Institution Endocrinological Research Center ( Site 0021)
city: Saint Petersburg
country: Russian Federation
facility: City children polyclinic #44 ( Site 0025)
city: Saint Petersburg
country: Russian Federation
facility: St.Petersburg State Pediatric Medical University ( Site 0023)
city: Ufa
country: Russian Federation
facility: Republic Children Clinical Hospital ( Site 0022)
city: Pretoria
country: South Africa
facility: Little Company of Mary Hospital ( Site 0017)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: