Efficacy and Safety Study of Triptorelin 3-Month Formulation in Chinese Children With Central Precocious Puberty.

An Open-label, Multicentre, Single Arm Study to Assess the Efficacy and Safety of Triptorelin 3-month Formulation in Chinese Children With Central Precocious Puberty

The purpose of this research was to confirm the effectiveness and safety of the study drug, Triptorelin pamoate 15mg 3-month formulation, in a Chinese population of Central Precocious Puberty (CPP) children.

Study Overview

• Status: Completed
• Conditions: Central Precocious Puberty
• Intervention / Treatment: Drug: Triptorelin pamoate 15mg

Detailed Description

For patients enter extension phase, two additional Triptorelin injections will be given at month 6 and month 9 visits.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Chengdu, China, 610073
    • Chengdu Women's and Children's Central Hospital
  • Nanchang, China, 330006
    • Jiangxi Provincial Children's Hospital
  • Nanjing, China, 210008
    • Children's Hospital of Nanjing
  • Tangshan, China, 063000
    • Tangshan Maternal & Child Health Hospital
  • Wuhan, China, 430030
    • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
  • Wuxi, China, 214023
    • Wuxi Children's Hospital
  • Zhengzhou, China, 450018
    • Henan Children's Hospital, Zhengzhou Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Onset of development of secondary sex characteristics before 8 and 9 years in girls and boys, respectively breast development in girls or testicular enlargement in boys according to the Tanner method: Stage II
• Pubertal response of LH to GnRH stimulation test (stimulated peak LH ≥5 IU/L)
• Difference between bone age (BA) (according to Greulich and Pyle method) and chronological age (CA) >1 year
• Girls with Tanner staging ≥2 for breast development and enlarged uterine length and several follicles with diameter >4 mm in the ovary at Screening visit; boys who have testicular volume ≥4 mL at Screening visit
• Age < 9 years old for girls and < 10 years old for boys at initiation of triptorelin treatment
• Weight at least 20 kg
• Subjects will qualify for the extension phase if they sign the corresponding specific consent form, are still benefiting from treatment at the end the primary study and have not experienced any unacceptable safety issues.

Exclusion Criteria:

• Gonadotropin-independent (peripheral) precocious puberty: extra pituitary 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
• Evidence of renal (creatinine >1.5 x upper limit of normal (ULN)) or hepatic impairment (bilirubin >1.5 x ULN or alanine aminotransferase (ALT)/aspartate transaminase (AST) >3 x ULN)
• Any other condition or chronic illness or treatment possibly interfering with growth or other study endpoints (e.g. chronic steroid use except topical steroids, renal failure, diabetes, moderate to severe scoliosis)
• Prior or current therapy with a GnRH agonist (GnRHa), medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1)
• Diagnosis of short stature, i.e. >2.25 standard deviation (SD) below the mean height for age
• Major medical or psychiatric illness that could interfere with study visits
• Known hypersensitivity to any of the test materials or related compounds
• 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 Pamoate 15mg for injection; Triptorelin was injected at day 1 and month 3. If participants were willing to enter the extension phase, two additional Triptorelin injections were given at month 6 and month 9.	Drug: Triptorelin pamoate 15mg; Intramuscular injection (IM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Luteinising Hormone (LH) Suppression After Gonadotropin-Releasing Hormone (GnRH) Stimulation	The LH suppression was defined as stimulated peak LH ≤3 International Units/Liter (IU/L). The GnRH stimulation test was performed by using an intravenous (IV) injection of gonadorelin (synthetic GnRH) to stimulate gonadotrophin release and blood samples were collected after the gonadorelin injection for central assessment of serum LH levels.	At Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Basal LH and Follicle-Stimulating Hormone (FSH) Serum Levels	Basal LH and FSH serum concentrations were analyzed centrally. Change from baseline was defined as the value for LH and FSH levels at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 3, 6, 9 and 12
Percentage of Participants With LH Suppression After GnRH Stimulation	A synthetic GnRH (gonadorelin) was used for gonadotrophin stimulation. Blood samples were collected prior to gonadorelin injection (timepoint T0) and at 30 minutes (T30), 60 minutes (T60) and 90 minutes (T90) (±5 minutes at each timepoint) after a single IV injection of gonadorelin. A suppressed LH response to GnRH stimulation test was defined as peak LH ≤3 IU/L among the 4 timepoints T0, T30, T60 and T90).	At Months 6 and 12
Change From Baseline in Peak LH and FSH Level After GnRH Stimulation	A synthetic GnRH was used for gonadotrophin stimulation. Blood samples were collected prior to gonadorelin injection (timepoint T0) and at 30 minutes (T30), 60 minutes (T60) and 90 minutes (T90) (±5 minutes at each timepoint) after a single IV injection of gonadorelin. The FSH response to GnRH stimulation was the peak FSH level among the 4 timepoints (T0, T30, T60 and T90). The LH response to GnRH stimulation test was defined as peak LH ≤3 IU/L among the 4 timepoints T0, T30, T60 and T90). Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 3, 6 and 12
Percentage of Participants With Prepubertal Levels of Sex Steroids	Prepubertal sex steroids assessment included estradiol in female participants and testosterone in male participants. Prepubertal sex steroids levels were defined as: estradiol ≤20 picogram (pg)/milliliter (mL) in female participants and testosterone ≤0.3 nanogram (ng)/mL in male participants.	At Months 3, 6, 9 and 12
Change From Baseline in Estradiol Levels	Estradiol serum concentration was analyzed centrally. Change from baseline was defined as the value for estradiol levels at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 3, 6 ,9 and 12
Change From Baseline in Testosterone Levels	Testosterone serum concentration was analyzed centrally. Change from baseline was defined as the value for testosterone levels at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 3, 6 ,9 and 12
Percentage of Participants With Change From Baseline in Pubertal Stage	Pubertal stage parameters were analyzed using Tanner method. Pubertal stage parameters included genital stage in male participants, breast stage in female participants and pubic hair stage in both sexes.	Baseline (Day 1) and at Months 6 and 12
Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline	Pubertal stage parameters were analyzed using Tanner method. Pubertal stage parameters included genital stage in male participants, breast stage in female participants and pubic hair stage in both sexes.	Baseline (Day 1) and at Months 6 and 12
Change From Baseline in Auxological Parameter: Height	Auxological parameter including height was analyzed. Change from baseline was defined as the value for each auxological parameter at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 3, 6, 9 and 12
Change From Baseline in Auxological Parameter: Weight	Auxological parameter including weight was analyzed. Change from baseline was defined as the value for each auxological parameter at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 3, 6, 9 and 12
Change From Baseline in Auxological Parameter: Growth Velocity	Auxological parameter including growth velocity was analyzed. Change from baseline was defined as the value for each auxological parameter at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 3, 6, 9 and 12
Change From Baseline in Auxological Parameter: Body Mass Index (BMI)	Auxological parameter including BMI was analyzed. Change from baseline was defined as the value for each auxological parameter at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 3, 6, 9 and 12
Change From Baseline in Bone Age (BA)	BA was determined using X-rays of the hand and wrist. Change from baseline was defined as the value for BA at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 6 and 12
Change From Baseline Difference Between BA and Chronological Age (CA)	BA was determined using X-rays of the hand and wrist. Change from baseline was defined as the difference between BA and CA value at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 6 and 12
Change From Baseline in Uterine Length	Uterine length was determined by type B ultrasound. Change from baseline was defined as the value of uterine length at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 6 and12
Change From Baseline of Testicular Volume	Testicular volume was determined by type B ultrasound. Change from baseline was defined as the value of testicular volume at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.	Baseline (Day 1) and at Months 6 and 12

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2021
• Primary Completion (Actual): February 9, 2022
• Study Completion (Actual): September 3, 2022

Study Registration Dates

• First Submitted: January 29, 2021
• First Submitted That Met QC Criteria: January 29, 2021
• First Posted (Actual): February 3, 2021

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

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-52014-243

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