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

Central Precocious Puberty Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05029622
• Other study ID #: D-CN-52014-244
• Secondary ID: 2022-003857-78
• Status: Completed
• Phase: Phase 3
• Start date: August 10, 2021
• Est. completion date: February 13, 2023

Study information

• Verified date: June 2024
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: February 13, 2023
• Est. primary completion date: August 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 10 Years

Eligibility

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.

Related Conditions & MeSH terms

• Central Precocious Puberty
• Puberty, Precocious

Intervention

Drug:
• Triptorelin Pamoate
Triptorelin 6-month formulation for IM on day 1 and Month 6.

Locations

Country	Name	City	State
China	Beijing Children's Hospital, Capital Medical University	Beijing
China	No.1 Hospital of Jilin University (Bethune first hospital of Jilin University)	Changchun
China	Children's Hospital of Fudan University	Changhai
China	Hunan children's hospital	Changsha
China	Chengdu Women's & Children's Central Hospital	Chengdu
China	Shandong Provincial Hospital	Jinan
China	Linyi Maternal and Child Health Care Hospital	Linyi
China	Jiangxi Provincial Children's Hospital	Nanchang
China	Pingxiang Maternity and Child Care	Pingxiang
China	Children's Hospital of Soochow University	Suzhou
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology	Wuhan
China	Wuhan Children's Hospital Tongji Medical College Huazhong University of Science & Technology	Wuhan
China	Wuxi children's Hospital	Wuxi
China	Zhengzhou Children's Hospital , Henan Children's Hospital	Zhengzhou

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Luteinising Hormone (LH) Suppression	LH response was defined as a peak LH <=5 international units per liter (IU/L) after intravenous (IV) gonadotropin-releasing hormone (GnRH) stimulation. The GnRH stimulation test was performed by using an 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. Percentage of response was calculated by number of participants in the specified category divided by number of participants in the analysis population multiplied by 100.	At Month 6
Secondary	Percentage of Participants With LH Response to GnRH Test	LH response was defined as a peak LH <=5 IU/L after IV GnRH stimulation. The GnRH stimulation test was performed by using an 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. Percentage of response was calculated by number of participants in the specified category divided by number of participants in the analysis population multiplied by 100.	At Months 3 and 12
Secondary	Change From Baseline in Basal Serum LH and Follicle-Stimulating Hormone (FSH) Levels	Basal LH and FSH serum concentrations were analyzed centrally. Change from baseline was defined as the values for LH and FSH at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first study treatment administered.	Baseline and at Months 3, 6, 9 and 12
Secondary	Change From Baseline in Peak Serum LH and FSH Level After the GnRH Stimulation Test	Peak LH and FSH serum concentrations were analyzed centrally. Change from baseline was defined as the values for LH and FSH at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first study treatment administered. Blood samples were collected prior to gonadorelin injection (timepoint T0) and at 30 minutes (T30), 60 minutes (T60) and 90 minutes (T90) after a single IV injection of gonadorelin. A suppressed LH response to GnRH stimulation test was defined as peak serum LH <=5 IU/L among the four timepoints (T0, T30, T60 and T90). The FSH response to GnRH stimulation was the peak serum FSH level among the four timepoints (T0, T30, T60 and T90).	Baseline and at Months 3, 6 and 12
Secondary	Percentage of Participants With LH Response (Peak LH <=5 IU/L) From Month 6 to Month 12	Peak LH serum concentration was analyzed centrally. LH response was defined as a peak LH <=5 IU/L after IV GnRH stimulation. The GnRH stimulation test was performed by using an IV injection of gonadorelin (synthetic GnRH) to stimulate gonadotrophin release and blood samples were collected after the gonadorelin injection for central assessment of peak LH levels. Percentage of response was calculated by number of participants in the specified category divided by number of participants in the analysis population multiplied by 100.	Month 6 to Month 12
Secondary	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 <=30 nanogram (ng)/ deciliter (dL) in male participants. Percentage of response was calculated by number of participants in the specified category divided by number of participants in the analysis population multiplied by 100.	At Months 3, 6, 9 and 12
Secondary	Change From Baseline in Mean Height for Age (Z-Score)	Z-scores are calculated using Centers for Disease Control and Prevention (CDC) Growth Charts. Change from baseline was defined as the values for Z-score at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to study treatment administration. Negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.	Baseline and at Months 6 and 12
Secondary	Change From Baseline in Percentile for Height for Age	Z-scores were calculated using CDC growth charts, that contained Box-Cox transformation (L), the median (M) and the generalized coefficient of variation (S). Percentile was obtained using the following equation M (1 + LSZ) ** (1/L), where ** indicated an exponent, such that m (1+LSZ)** (1/L) meant raising (1+LSZ) to the (1/L)th power and then multiplying the M. Z was the Z-score that corresponds to the percentile. Negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline was defined as the values for percentile of Z-score at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first study treatment administered.	Baseline and at Months 6 and 12
Secondary	Change From Baseline in Growth Velocity	Growth velocity analysis was part of auxological parameter. 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 study treatment administered.	Baseline and at Months 6 and 12
Secondary	Percentage of Participants With Bone Age (BA)/Chronological Age (CA) Ratio Not Risen	BA was determined using X-rays of the hand and wrist by Greulich and Pyle method. CA was calculated as (visit date -birth date + 1)/365.25. Percentage of response was calculated as n/N*100, where n was number of participants in the specified category and N was number of participants in the analysis population.	At Months 6 and 12
Secondary	Change From Baseline in BA:CA Ratio	BA was determined using X-rays of the hand and wrist by Greulich and Pyle method. CA was calculated as (visit date -birth date + 1)/365.25. Change from baseline was defined as the values for BA:CA ratio at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first study treatment administered.	Baseline, Months 6 and 12
Secondary	Percentage of Participants With Stabilized Pubertal Stage	Pubertal stage parameters were analyzed using Tanner method. Pubertal stage parameters included genital development stage (GDS) in male participants, breast development stage (BDS) in female participants and pubic hair development (PHD) stage in both sexes. Percentage of response was calculated by number of participants in the specified category divided by number of participants in the analysis population multiplied by 100.	At Months 6 and 12
Secondary	Percentage of Participants With Regression of Uterine Length	Uterine length was determined by transabdominal ultrasound. Percentage of response was calculated by number of participants in the specified category divided by number of participants in the analysis population multiplied by 100.	At Months 6 and 12
Secondary	Percentage of Participants With Absence of Progression of Testis Volumes	Testis volume was a clinical assessment with orchidometer. Percentage of response was calculated by number of participants in the specified category divided by number of participants in the analysis population multiplied by 100.	At Months 6 and 12
Secondary	Change From Baseline in Body Mass Index (BMI)	BMI analysis was part of auxological parameter assessment. 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 study treatment administered.	Baseline and at Months 6 and 12
Secondary	Change From Baseline in Weight	Weight analysis was part of auxological parameter assessment. 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 study treatment administered.	Baseline and at Months 6 and 12
Secondary	Plasma Concentrations of Triptorelin	Blood samples were collected at specified timepoints.	Day 1, 4 hours post-injection; Month 3; Month 6, predose; Month 6, 4 hours post-injection; and Month 12