A Study to Assess the Efficacy and Safety of the Triptorelin 6-month Formulation in Paediatric Participants With Central Precocious Puberty.

A Phase III, Open-label, Multicentre, Single Arm Study to Assess the Efficacy and Safety of the Triptorelin 6-month Formulation in Chinese Paediatric Participants With Central Precocious Puberty.

The purpose of the protocol is to assess the efficacy of the triptorelin 6 month PR (Prolonged Release) formulation in suppressing LH (Luteinising hormone) levels to prepubertal levels (defined as a peak LH ≤5 IU/L) after i.v. GnRH (Gonadotropin-releasing Hormone) stimulation at Month 6 (Day 169) in Chinese children with CPP (Central Precocious Puberty).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100045
    • Beijing Children's Hospital, Capital Medical University
  • Changchun, China, 130021
    • No.1 Hospital of Jilin University (Bethune first hospital of Jilin University)
  • Changhai, China, 201102
    • Children's Hospital of Fudan University
  • Changsha, China, 410007
    • Hunan Children's Hospital
  • Chengdu, China, 610073
    • Chengdu Women's & Children's Central Hospital
  • Jinan, China, 250021
    • Shandong Provincial Hospital
  • Linyi, China, 276016
    • Linyi Maternal and Child Health Care Hospital
  • Nanchang, China, 330006
    • Jiangxi Provincial Children's Hospital
  • Pingxiang, China, 337000
    • Pingxiang Maternity and Child Care
  • Suzhou, China, 215031
    • Children's Hospital of Soochow University
  • Wuhan, China, 430030
    • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
  • Wuhan, China, 430015
    • Wuhan Children's Hospital Tongji Medical College Huazhong University of Science & Technology
  • Wuxi, China, 214023
    • Wuxi Children's Hospital
  • Zhengzhou, China, 450018
    • Zhengzhou Children's Hospital , Henan Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant is less than 9 years old for girls and less than 10 years old for boys at initiation of triptorelin treatment or at the time of signing the informed consent.
• Participant must present evidence of CPP documented by:
• Onset of development of secondary sex characteristics (breast development in girls or testicular enlargement in boys according to the Tanner method: Stage II) before the age of 8 years in girls and 9 years in boys.
• Pubertal response of LH to GnRH stimulation test (stimulated peak LH ≥6 IU/L) in both sexes.
• Difference between bone age (BA) and CA >1 year.
• Girls with Tanner staging ≥2 for breast development and who have enlarged uterine length and/or ovarian volume and at last 2 follicles with diameter >4 mm in the ovary observed by pelvic type B ultrasound at the Screening visit; boys who have testicular volume ≥4 mL observed by testicular orchidometer at the Screening visit.
• Girls who have already had menophania/menarche must have a negative highly sensitive (urine) pregnancy test as required by local regulations within 24 hours before the first dose of study intervention and should not be at risk of pregnancy throughout the study period.

Exclusion Criteria:

• Gonadotropin-independent (peripheral) precocious puberty: extrapituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion.
• Non-progressing isolated premature thelarche.
• Presence of an unstable intracranial tumour or an intracranial tumour requiring neurosurgery or cerebral irradiation. Participants with hamartomas not requiring surgery are eligible.
• Prior or current therapy with a GnRHa (Gonadotropin-releasing Hormone Agonist) , medroxyprogesterone acetate, growth hormone or insulin-like growth factor 1 (IGF 1).Use of anticoagulants (heparin and coumarin derivatives) within the 2 weeks prior to the Screening visit.

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: Triptorelin formulation for Intramuscular injection (IM).	Drug: Triptorelin Pamoate; Triptorelin 6-month formulation for IM on day 1 and Month 6.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of children with LH (Luteinising Hormone) suppression defined as stimulated peak LH ≤5 IU/L after GnRH (Gonadotropin-releasing Hormone) stimulation.	At month 6.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of children with LH response to GnRH test.		At months 3 and month 12.
Change from basal serum LH levels.		At months 3, 6, 9 and 12.
Change from baseline in basal FSH (Follicle-stimulating Hormone) levels		At months 3,6, 9 and 12
Change from baseline in peak serum LH levels after the GnRH stimulation test		At months 3, 6 and 12.
Change from baseline in peak serum FSH levels after the GnRH stimulation test		At months 3, 6 and 12.
Proportion of children with pre-pubertal levels of sex steroids.	Defined as oestradiol ≤20 pg/mL in girls or testosterone ≤30 ng/dL in boys	Months 3, 6, 9 and 12.
Change from baseline in height-for-age Z-score		At months 6 and 12.
Change from baseline in height-for-age percentile		At months 6 and 12.
Change from baseline in growth velocity		At months 6 and 12.
Proportion of children in whom the BA/CA (Bone Age/Chronological Age) ratio did not rise (X ray).		At months 6 and 12.
Change in the ratio BA/CA		At months 6 and 12.
Proportion of children who achieve stabilisation of sexual maturation compared to baseline stage using Tanner method.		At months 6 and 12.
Proportion of girls with regression of uterine length	Clinical assessment with transabdominal ultrasound	At months 6 and 12.
Proportion of boys with absence of progression of testis volumes	Clinical assessment with orchidometer.	At month 6 and 12.
Change in BMI (Body Mass Index).		At months 6 and 12.
Change in weight.		At months 6 and 12.
Incidence of TEAEs (treatment-emergent adverse events), including local tolerability at the injection site.		1 year, including immediately and 2 hours after triptorelin injection.
Change in clinical safety laboratory: blood biochemistry parameters. (Creatinine, Non fasting Glucose, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase, Total and direct bilirubin, Calcium, Phosphorous),	Any abnormal laboratory test results or other safety assessments, including those that worsen from baseline, considered clinically significant in the medical and scientific judgment of the investigator	At month 3, 6, 9 and 12.
Change in clinical safety laboratory haematology parameters (Complete blood count).		At month 3, 6, 9 and 12.
Change in clinical safety laboratory urinalysis parameters (Specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick).		At month 3, 6, 9 and 12.
Change in physical examination.	A complete physical examination will include, assessments of the cardiovascular, respiratory, gastrointestinal and neurological systems. Height and weight.	At day 1, months 3, 6, 9 and 12.
Change in vital signs: Change in heart rate.		At day 1, months 3, 6, 9 and 12.
Change in vital signs: Change in blood pressure.		At day 1, months 3, 6, 9 and 12.
Sparse plasma triptorelin concentrations		At day 1, months 3, 6 and 12.

Collaborators and Investigators

• Sponsor: Ipsen

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2021
• Primary Completion (Actual): August 21, 2022
• Study Completion (Actual): February 13, 2023

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Luteolytic Agents; Triptorelin Pamoate
• Other Study ID Numbers: D-CN-52014-244

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No