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)

NCT03019575 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: 8962-0432015-001878-18MK-8962-043
• Study Type: interventional
• Target: 17
• Locations: 6 countries
• Sites: 15

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

Conditions

Hypogonadotropic Hypogonadism

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  Up to approximately 71 Weeks

• Number of Participants Who Discontinued Study Treatment Due to an 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 discontinued study treatment due to an AE was reported.

  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.

  Up to approximately 71 Weeks

Secondary Outcomes (13)

• Change From Baseline in Serum Inhibin B Concentration to Week 64

  Baseline and Week 64

• Growth Velocity at Week 36

  Week 36

• Growth Velocity at Week 64

  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 TS of Pubertal Development for Genital Growth to Week 12, Week 36, and Week 64

  Baseline, Week 12, Week 36, and Week 64

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: Corifollitropin alfa; Drug: hCG

Interventions

Corifollitropin alfa DRUG

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).

Also known as: MK-8962, Elonva

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

hCG DRUG

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).

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

Eligibility Criteria

• Age: 14 Years - 17 Years
• Gender Eligibility Details: All participants must be male.
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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).

Sponsors & Collaborators

• Organon and Co: lead

Study Sites (15)

Centro de Diabetes Curitiba ( Site 0012)

Curitiba, 80810-040, Brazil

Location

Hospital de Clinicas de Porto Alegre ( Site 0014)

Porto Alegre, 90035-903, Brazil

Location

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

São Paulo, 05403-000, Brazil

Location

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

Copenhagen, 2100, Denmark

Location

AOU Careggi ( Site 0042)

Florence, 50139, Italy

Location

Policlinico Umberto I ( Site 0043)

Roma, 00161, Italy

Location

IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0044)

Roma, 00165, Italy

Location

Instituto Nacional de Pediatria ( Site 0007)

Mexico City, 04530, Mexico

Location

Hospital Infantil de Mexico Federico Gomez ( Site 0006)

Mexico City, 06720, Mexico

Location

Kazan State Medical University ( Site 0024)

Kazan', 420048, Russia

Location

Federal State Budget Institution Endocrinological Research Center ( Site 0021)

Moscow, 117036, Russia

Location

City children polyclinic #44 ( Site 0025)

Saint Petersburg, 191144, Russia

Location

St.Petersburg State Pediatric Medical University ( Site 0023)

Saint Petersburg, 194100, Russia

Location

Republic Children Clinical Hospital ( Site 0022)

Ufa, 450106, Russia

Location

Little Company of Mary Hospital ( Site 0017)

Pretoria, 0181, South Africa

Location

MeSH Terms

Conditions

Hypogonadism

Interventions

follicle stimulating hormone, human, with HCG C-terminal peptide

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Results Point of Contact

• Title: Clinical Trials Disclosure
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2017
• First Posted: January 12, 2017
• Study Start: February 2, 2017
• Primary Completion: May 5, 2020
• Study Completion: May 5, 2020
• Last Updated: May 23, 2024
• Results First Posted: April 8, 2021

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); RU (5); BR (3); ZA (1); DK (1); ME (2)