A Study to Assess the Efficacy and Safety of the Triptorelin 6-month Formulation in Paediatric Participants With Central Precocious Puberty.
Study Details
Study Description
Brief 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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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. [Months 3, 6, 9 and 12.]
Defined as oestradiol ≤20 pg/mL in girls or testosterone ≤30 ng/dL in boys
- 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 [At months 6 and 12.]
Clinical assessment with transabdominal ultrasound
- Proportion of boys with absence of progression of testis volumes [At month 6 and 12.]
Clinical assessment with orchidometer.
- 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), [At month 3, 6, 9 and 12.]
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
- 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. [At day 1, months 3, 6, 9 and 12.]
A complete physical examination will include, assessments of the cardiovascular, respiratory, gastrointestinal and neurological systems. Height and weight.
- 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.]
Eligibility Criteria
Criteria
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:
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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.
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Girls with Tanner staging ≥2 for breast development and who have enlarged uterine length and/or ovarian volume and several 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.
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Non-progressing isolated premature thelarche.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Children's Hospital, Capital Medical University | Beijing | China | 100045 | |
| 2 | No.1 Hospital of Jilin University (Bethune first hospital of Jilin University) | Changchun | China | 130021 | |
| 3 | Children's Hospital of Fudan University | Changhai | China | 201102 | |
| 4 | Hunan children's hospital | Changsha | China | 410007 | |
| 5 | Chengdu Women's & Children's Central Hospital | Chengdu | China | 610073 | |
| 6 | The children's hospital Zhejiang university school of medicine | Hangzhou | China | 310000 | |
| 7 | Shandong Provincial Hospital | Jinan | China | 250021 | |
| 8 | Linyi Maternal and Child Health Care Hospital | Linyi | China | 276016 | |
| 9 | Jiangxi Provincial Children's Hospital | Nanchang | China | 330006 | |
| 10 | Pingxiang Maternity and Child Care | Pingxiang | China | 337000 | |
| 11 | Children's Hospital of Soochow University | Suzhou | China | 215031 | |
| 12 | Wuhan Children's Hospital Tongji Medical College Huazhong University of Science & Technology | Wuhan | China | 430015 | |
| 13 | Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology | Wuhan | China | 430030 | |
| 14 | Wuxi children's Hospital | Wuxi | China | 214023 | |
| 15 | Zhengzhou Children's Hospital , Henan Children's Hospital | Zhengzhou | China | 450018 |
Sponsors and Collaborators
- Ipsen
Investigators
- Study Director: Ipsen Medical Director, Ipsen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D-CN-52014-244