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

Study Overview
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Brief Summary
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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).

Official Title
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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.

Conditions
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Central Precocious Puberty

Intervention / Treatment
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* Drug: Triptorelin Pamoate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triptorelin formulation for Intramuscular injection (IM).<br> | Drug: Triptorelin Pamoate<br>* Triptorelin 6-month formulation for IM on day 1 and Month 6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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. |