A Study to Assess the Safety and Efficacy of Leuprorelin in Central Precocious Puberty in Chinese Participants

An Open Label, Multicenter Study to Assess the Safety and Efficacy of Leuprorelin in the Treatment of Central Precocious Puberty

The purpose of this study is to assess long-term safety and efficacy of leuprorelin in the treatment of Central Precocious Puberty (CPP).

Study Overview

• Status: Completed
• Conditions: Central Precocious Puberty
• Intervention / Treatment: Drug: Leuprorelin

Detailed Description

The drug in this study is called leuprorelin. It is administered as a 1 month subcutaneous depot injection. Leuprorelin is used to treat children who have CPP. This study will look at whether leuprorelin can stop early puberty in pre-pubertal children.

The study will enroll approximately 300 participants. Participants with body weight >=20 kg will receive the recommended dose of leuprorelin 3.75 mg subcutaneous injection every 4 weeks for 96 weeks. Participants with body weight <20 kg will receive recommended dose of 1.88 mg subcutaneous injection every 4 weeks for 96 weeks.

This trial will be conducted in China. The overall time to participate in this study is 104 weeks. Participants will make 11 visits to the clinic, and will be followed-up by the physician on a long-term basis until stable puberty is reached.

• Study Type: Interventional
• Enrollment (Actual): 307
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
  • Hubei
    • Wuhan, Hubei, China
  • Hunan
    • Changsha, Hunan, China
  • Jiangsu
    • Nanjing, Jiangsu, China
    • Wuxi, Jiangsu, China
  • Jiangxi
    • Nanchang, Jiangxi, China
  • Jilin
    • Changchun, Jilin, China
  • Shanghai
    • Shanghai, Shanghai, China
  • Zhejiang
    • Hangzhou, Zhejiang, China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. In the opinion of the investigator, the participant and/or parent(s) or legal guardian are capable of understanding and complying with protocol requirements.
2. The participant or the participant's parent(s) or legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Has onset of appearance of secondary sexual characteristic earlier than age 8.0 years in girls or earlier than 9.0 years in boys and the symptom is persistent, and has confirmed diagnosis of CPP.
4. Has basal luteinizing hormone (LH) level greater than (>) 5.0 international units per liter (IU/L) or peak LH >3.3 IU/L with LH/follicle-stimulating factor (FSH) >0.6 in stimulation test.
5. Has evidence of gonadal development evaluated by ultrasonography: ovarian volume >=1 milliliter (mL) with multiple follicles >=4 millimeter (mm) in any ovary or uterine enlargement in females or testicular volume >=4 mL in males.
6. Has advanced bone age (BA) >=1 year and BA is less than or equal to (<=) 11.5 years in females or <=12.5 years in males OR predicted adult height <150 centimeter (cm) in females or <160 cm in males OR standard deviation score (SDS) <-2 standard deviations (SD) OR rapid growth defined as growth of BA /growth of chronologic age >1. BA is determined by Greulich and Pyle standards or Tanner-Whitehouse 3 (TW3) standards at screening.
7. Has anticipated treatment duration of at least 2 year in investigator's judgment.
8. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 90 days after last dose.
9. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.
10. The female participant who, at the discretion of the investigator, is deemed to be of child bearing potential must provide negative urine pregnancy text at Day -1 or Day 1 prior to drug administration.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to Screening.
2. Has received gonadotropin-releasing hormone analog (GnRHa) treatment in a previous clinical study or as a therapeutic agent.
3. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example [eg], spouse, parent, child, sibling) or may consent under duress.
4. Has any findings in his/her medical history, physical examination, or safety clinical laboratory tests giving reasonable suspicion of underlying disease that might interfere with the conduct of the trial.
5. Has any concomitant medical condition that, in the opinion of the investigator, may expose a participant to an unacceptable level of safety risk or that affects participant compliance.
6. Has any screening abnormal laboratory value that suggests a clinically significant underlying disease or condition that may prevent the participant from entering the study; or the participant has: creatinine >=1.5 milligram per deciliter (mg/dL), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2 times the upper limit of normal (ULN), or total bilirubin >2.0 mg/dL, with AST/ALT elevated above the limits of normal values.
7. Has a history or clinical manifestations of significant adrenal or thyroid diseases or intracranial tumor OR has a history of malignant disease.
8. Has a history of hypersensitivity or allergies to leuprorelin, or related compounds including any excipients of the compound.
9. Has a diagnosis of peripheral precocious puberty.
10. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening Visit.
11. Participant or parent(s), at the discretion of the investigator, is unlikely to comply with the protocol or is unsuitable for any of other reason.
12. If female, the participant is of childbearing potential (eg, not sterilized).
13. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
14. If male, the participant intends to donate sperm during the course of this study or for 90 days thereafter.
15. Has participated in another clinical study and/or has received any investigational compound within 30 days prior to Screening.

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; Participants with body weight greater than or equal to (>=) 20 kilogram (kg) will receive the recommended dose of leuprorelin 3.75 milligram (mg), injection, subcutaneously, once every 4 weeks for 96 weeks. Participants with body weight less than (<) 20 kg will receive leuprorelin 1.88 mg, injection, subcutaneously, once every 4 weeks for 96 weeks.	Drug: Leuprorelin; Suspension for injection.; Other Names: Enantone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	Day 1 up to Week 100

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Regression or no Progression in Tanner Staging at Week 96	Tanner assessment score was used to document the stage of development of puberty through the assessment of secondary sexual characteristics. Female pubertal development staged by pubic hair development and breast size; male pubertal development staged by size of the genitalia and development of pubic hair. Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). Regression or no progression was defined as negative change (improvement) or no change in Tanner score at Week 96 compared to baseline.	Week 96

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Luo X, Hou L, Zhong Y, You C, Yang Y, Wu X, Li P, Zhou S, Qiu W, Zhang H, Liu Y, Qian Y, Luo F, Cheng R, Hu Y, Gong H, Wang Q, Xu Z, Du H, Lu F, Fu J, Chen X, Wang W, Guo Z. An open label, multicenter clinical trial that investigated the efficacy and safety of leuprorelin treatment of central precocious puberty in Chinese children. Medicine (Baltimore). 2021 Dec 23;100(51):e28158. doi: 10.1097/MD.0000000000028158.

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2015
• Primary Completion (Actual): November 23, 2018
• Study Completion (Actual): November 23, 2018

Study Registration Dates

• First Submitted: April 23, 2015
• First Submitted That Met QC Criteria: April 23, 2015
• First Posted (Estimate): April 28, 2015

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: Leuprorelin-4001; U1111-1183-0353 (Registry Identifier: WHO); CTR20140148 (Registry Identifier: SFDA CTR)

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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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