Efficacy and Safety of Leuprolide Acetate 45 mg in Subjects With Central Precocious Puberty (NEST)

An Open Label, Single-group, Multicenter Study on the Efficacy and Safety of Leuprolide Acetate 45 mg for Injectable Suspension-controlled Release in Subjects With Central (Gonadotropin-dependent) Precocious Puberty

This study is a multicenter, open-label, single-group, and phase 4 study to evaluate the efficacy and safety of 45 mg of leuprolide acetate in CPP.

Screening tests are performed after the subject agrees in writing to participate in the clinical trial, and subjects who meet the inclusion criteria and do not fall under the exclusion criteria are enrolled in the study. The target patients in this study are pediatric patients who have been diagnosed with CPP but have not yet received GnRH agonist treatment, and all subjects perform GnRH stimulation tests to confirm their CPP diagnosis.

Study Overview

• Status: Recruiting
• Conditions: CPP
• Intervention / Treatment: Drug: Eligard® 45 mg

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sunmi Park; Phone Number: 0222041763; Email: parksm@hanall.com

Study Locations

• Korea, Republic of
  • Ansan, Korea, Republic of
    • Recruiting
    • Korea University Ansan Hospital
    • Contact: In kyung Choi
    • Contact: Eungu Kang
  • Jeonju, Korea, Republic of
    • Recruiting
    • Jeonbuk National University Hospital
    • Contact: Yoon Ja Lee
    • Contact: Min Sun Kim
  • Kwangju, Korea, Republic of
    • Recruiting
    • Chosun university hospital
    • Contact: Hye Sun Byeon
    • Contact: Eun Young Kim
  • Seongnam, Korea, Republic of
    • Recruiting
    • Seoul National University Bundang Hospital
    • Contact: Gun Hyun Lee
    • Contact: Jaehyun Kim
  • Seoul, Korea, Republic of
    • Recruiting
    • Asan Medical Center
    • Contact: Ji Won Kim
    • Contact: Jin-Ho Choi
  • Seoul, Korea, Republic of
    • Recruiting
    • Gangnam Severance Hospital
    • Contact: Ha Na Lee
    • Contact: Hyun Wook Chae
  • Seoul, Korea, Republic of
    • Recruiting
    • Kangdong Sacred Heart Hospital
    • Contact: Hyun Jung Kim
    • Contact: Il tae Hwang
  • Seoul, Korea, Republic of
    • Recruiting
    • Kyung Hee University Hospital at Gangdong
    • Contact: Seul Ki Lee
    • Contact: Kye Shik Shim
  • Suwon, Korea, Republic of
    • Recruiting
    • Ajou University Medical Center
    • Contact: Bo Ra Lim
    • Contact: Hae Sang Lee
    • Contact: Young Suk Shim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pubertal-type LH response following an abbreviated GnRH stimulation test before treatment initiation > 5 IU/L
2. A subject manifested with central precocious puberty according to the following criteria Age : Boy (4 years of age or older ~ under 9 years of age) Girl (4 years of age or older ~ under 8 years of age) Tanner Stage : Level 2 or higher
3. Based on baseline visit (Day 0), those under the age of 10 for boys and those under the age of 9 for girls
4. Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have not received prior GnRH agonist treatment for CPP
5. Children with a body weight of more than 20 kg at screening
6. Children have a bone age that is ≥1 year older than their chronological age at screening
7. A signed written consent form by a legal representative who has been informed about this study

Exclusion Criteria:

1. Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion
2. Prior or current GnRH treatment for CPP
3. Non-progressing isolated premature thelarche
4. Presence of an unstable intracranial tumor or an intracranial tumor requiring neurosurgery or cerebral irradiation. Subjects with hamartomas not requiring surgery are eligible.

5. Prior (within 12 weeks of Screening) use of medications

   • Hormonal agonists (Estrogen, Progesterone, FSH, LH, Testosterone etc.)
   • Hormonal antagonists (Anti-Estrogen agents, Anti-Androgen agents)
   • Steroid use (except for mild topical steroids, oral steroids are allowed within 30 days)
   • Herbal Medicines
6. Prior or current therapy with growth hormone
7. Major medical or psychiatric illness that could interfere with study visits
8. Diagnosis of short stature (i.e. 2 standard deviations (SD) below the mean height for age or 3rd percentile for age)
9. Pregnant or likely pregnant women (Positive urine pregnancy test), nursing women
10. Known hypersensitivity to GnRH or related compounds
11. Any other medical condition or serious intercurrent illness that, in the opinion of the investigator, may make it undesirable for the subject to participate in the study
12. Any other condition(s) which could significantly interfere with Protocol compliance
13. Treatment with an investigational product within 5 half-lives of that product in prior clinical studies before the baseline visit (Day 0)
14. Known history of seizures, epilepsy, and/or central nervous system disorders that may be associated with seizures or convulsions
15. Prior (within 6 months of Baseline (Day 0)) or current use of medications that, per investigator opinion, have been associated with seizures or convulsions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eligard® 45 mg; SC injection of study drug (45 mg of leuprolide acetate for injectable suspensions)	Drug: Eligard® 45 mg; 45 mg of leuprolide acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage (%) of subjects with serum LH concentrations < 4 IU/L following an GnRH stimulation test	Blood samples for serum LH concentrations (as appropriate) will be collected at the appropriate assessment times and analyzed by a central laboratory.	at week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage (%) of subjects with suppressed serum LH concentrations (< 4 IU/L) 30-minutes post GnRH stimulation test	Blood samples for serum LH concentrations (as appropriate) will be collected at the appropriate assessment times and analyzed by a central laboratory.	at week 12, 48, 72, 96
The percentage (%) of subjects with suppressed serum FSH (< 2.5 mIU/mL), estradiol (< 20 pg/mL, for girl) or testosterone (< 30 ng/dL, for boy)	Sexual development in puberty will be assessed by Tanner staging	at week 12, 24, 48, 72, 96
The percentage of subject of Tanner stage (including menstruation)	Sexual development in puberty will be assessed by Tanner staging	at week 12, 24, 48, 72, 96
Height velocity (growth rate)	Annualized Height Velocity	at week 12, 24, 48, 72, 96
The ratio of bone age and chronological age	A single X-ray of the non-dominant hand and wrist will be obtained periodically	at week 12, 24, 48, 72, 96

Collaborators and Investigators

• Sponsor: HanAll BioPharma Co., Ltd.
• Investigators: Study Director: Eunhee Lee, Hanall Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2024
• Primary Completion (Estimated): April 20, 2026
• Study Completion (Estimated): October 30, 2027

Study Registration Dates

• First Submitted: April 8, 2025
• First Submitted That Met QC Criteria: April 8, 2025
• First Posted (Actual): April 15, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious; Antineoplastic Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: HLA24IV_1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes