A Study of Leuprolide Acetate Depot in Children With Central Precocious Puberty (PUPIL)

An Open Label, Multicenter, Single-arm and Prospective Study to Assess the Efficacy and Safety of Leuprorelin 3M in the Treatment of Central Precocious Puberty (CPP)

The main aim is to see how leuprolide works to treat central precocious puberty in children. Participants will receive an injection of leuprorelin acetate depot 11.25 mg every 12 weeks during 6 months and will visit their study clinic 6 times to complete some assessments.

Study Overview

• Status: Completed
• Conditions: Central Precocious Puberty
• Intervention / Treatment: Drug: Leuprorelin Acetate Depot 3M

Detailed Description

The drug being tested in this study is called leuprorelin acetate depot 3M. Leuprorelin acetate depot 3M will be tested to treat children who have central precocious puberty. This study will look at the efficacy and safety of leuprorelin acetate depot 3M in the treatment of CPP.

The study will enroll approximately 80 participants with CPP. Participants with a bodyweight of ≥ 20 kg will receive the recommended dose of leuprorelin acetate depot 3M in a 24 weeks Treatment Period followed by a 12 weeks Post-treatment follow-up period. Participants will be assigned to the following drug administration:

• Leuprorelin Acetate Depot 3M 11.25 mg

Participants will receive leuprorelin acetate depot 3M 11.25 mg as subcutaneous (SC) injection on Weeks 0, 12, and 24. The gonadotropin-releasing hormone agonist (GnRHa) stimulation, basal luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels will be tested pre-dose of every SC injection of the study drug or at premature termination.

This multi-center trial will be conducted in China. The overall time to participate in this study is 38 weeks. Participants will make a follow-up visit to the site at approximately 12 weeks after the last dose of study treatment.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100033
      • Beijing Children's Hospital, Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510062
      • the First A liated Hospital of Sun Yat-sen University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • The Hospital attached by the Torigji Medical College, Huazhong Science and Technology University.
  • Shandong
    • Jinan, Shandong, China, 250021
      • Provincial Hospital Affiliated to Shandong First Medical University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200062
      • Shanghai Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 9 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Maximum age to participate is this study is up to 10 years (child). Early appearance of secondary sexual characteristics: Girls ≤8 years, Boys ≤9years
2. Body weight ≥20 kg
3. According to the National Consensus Statement in China (2015), CPP is diagnosed when secondary sexual characteristics appeared before the age of 8 years in girls and 9 years in boys, a peak LH level >5.0 IU/L with LH/FSH >0.6 in stimulating test; evidence of gonadal development by ultrasonography (multiple ovarian follicles ≥4 mm in any ovary or uterine enlargement in females or testicular volume ≥4 mL in males); advanced bone age (BA) ≥1 year; linear growth acceleration with higher growth velocity (GV) than normal children. BA is determined by Greulich and Pyle standards or TW3 standards at screening.

Exclusion Criteria:

1. The participant has received GnRHa treatment in a previous clinical study or as a therapeutic agent.
2. The participant has a history or clinical manifestations of significant adrenal or thyroid diseases or intracranial tumor OR has a history of malignant disease.
3. The participant has a history of hypersensitivity or allergies to leuprorelin, or related compounds including any excipients of the compound.
4. The participant has a diagnosis of peripheral precocious puberty.

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: Leuprorelin Acetate Depot 3M 11.25 mg; Participants with CPP having body weight greater than equal to (≥)20 kilograms (kg) received the recommended dose of leuprorelin acetate depot 11.25 milligrams (mg) subcutaneous administration (SC) every 12 weeks based on the standard of 30～180 micrograms (μg)/kg/4 weeks for the 24-week Treatment Period. It was not recommended to exceed the dose above 180 μg/kg.

Drug: Leuprorelin Acetate Depot 3M; Leuprorelin Acetate Depot 3M SC injections.; Other Names: Leuprolide acetate Depot 3M

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Peak Luteinizing Hormone (LH) Suppression in Gonadotropin-Releasing Hormone (GnRH) Stimulation at Week 24	The LH suppression was defined as LH peak value in GnRH stimulation ≤3.0 international unit per liter (IU/L).	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Tanner Stage Regression or No Progression at Week 24	Tanner Stage was used to measure pubertal development. Tanner Stage was based on progression through 5-stages. The progression was defined as either breast/genitals or pubic hair score had increased score compared with baseline score. Otherwise, the status was classified as regression or no progression. Baseline is defined as the assessment prior to the first dose of study drug.	Baseline and Week 24
Concentrations of Basal Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH)	Plasma LH and FSH peak concentrations under GnRH stimulation were assessed.	Baseline, Weeks 24 and 36
Percentage of Participants With Decreased Ratio of Bone Age Over Chronological Age at Week 24	Bone age was determined by Greulich and Pyle standards or Tanner-Whitehouse 3 (TW3) standards.	Baseline and Week 24
Percentage of Participants With Decreased First Morning Voided (FMV) Urinary Gonadotropin (Gn) at Week 24		Baseline and Week 24
Number of Participants With Treatment-Emergent Adverse Events (TEAE)	An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAE is defined as an AE with an onset that occurs after receiving study drug.	From first dose of study drug up to 12 weeks post last dose or early termination Visit (ET) (up to approximately 36 weeks)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Actual): December 19, 2024
• Study Completion (Actual): March 10, 2025

Study Registration Dates

• First Submitted: April 18, 2022
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Drug Therapy
• 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: Leuprorelin-4002; 2022-002471-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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