Efficacy, Metabolism and BMD of the 3-month TP Compared to the 1-month TP in ICPP

NCT ID: NCT06487143

Last Updated: 2024-07-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-01
• Study Completion Date: 2026-12-30

Brief Summary

The primary objective of this study is to compare the efficacy of the 3-month formulation and 1-month formulation of triptorelin and to assess the short-term effects of the 3-month formulation of triptorelin on glucose and lipid metabolism, body composition, and bone density in Chinese ICPP patients.

Detailed Description

Idiopathic central precocious puberty (CPP) is an important treatable disease causing pubertal growth disorders. Gonadotropin-releasing hormone analogs (GnRHa) are the first-line drugs for treating idiopathic central precocious puberty (ICPP). Currently, the 1-month formulation (3.75mg) is the most widely used in China. The development of long-acting formulations will reduce the number of injections and treatment costs for children, as well as reduce the clinical visit burden. The 3-month formulation of Triptorelin Pamoate (15mg) was approved for use in central precocious puberty in March 2023. At present, there is only one publicly reported small-sample, single-arm clinical study in China, and there are no large-sample, real-world, concurrent controlled clinical study data on the efficacy and safety of the 3-month and 1-month formulations of triptorelin in the treatment of central precocious puberty. In currently reported safety events both domestically and internationally, there are no reports on the effects of the 3-month formulation of triptorelin on patients' glucose and lipid metabolism, body composition, and bone density. Our research team previously observed in a small-sample retrospective study of female patients with ICPP that after 1 year of treatment with the 3-month formulation of GnRHa (11.25mg leuprorelin), it effectively inhibited the hypothalamic-pituitary-gonadal axis and bone age progression, improved predicted adult height, and had no serious safety events. Therefore, based on our previous work, we plan to conduct a large-sample, real-world, concurrent controlled study to evaluate the gonadal axis suppression and predicted adult height benefits of the 3-month formulation of triptorelin compared to the 1-month formulation in patients with central precocious puberty (CPP). Additionally, we will assess the short-term effects of the 3-month formulation of triptorelin on glucose and lipid metabolism, body composition, and bone density in ICPP patients. The study results are expected to provide clinical evidence for the application of the 3-month formulation in the treatment of central precocious puberty in China.

Conditions

Central Precocious Puberty

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

3-month triptorelin

Triptorelin pamoate is administered via intramuscular injection once every three months

Group Type: EXPERIMENTAL

Triptorelin pamoate（15mg）

Intervention Type: DRUG

Triptorelin pamoate 15mg is administered via intramuscular injection once every three months.

1-month triptorelin

Triptorelin acetate 3.75mg is administered via intramuscular injection once every four weeks.

Group Type: ACTIVE_COMPARATOR

Triptorelin acetate （3.75mg）

Intervention Type: DRUG

Triptorelin acetate 3.75mg is administered via intramuscular injection once every four weeks.

Interventions

Triptorelin pamoate（15mg）

Triptorelin pamoate 15mg is administered via intramuscular injection once every three months.

Intervention Type: DRUG

Triptorelin acetate （3.75mg）

Triptorelin acetate 3.75mg is administered via intramuscular injection once every four weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Early appearance of secondary sexual characteristics, specifically breast development in girls before 8 years old or menarche before 10 years old, and testicular enlargement in boys before 9 years old.

2. Gonadal enlargement: pelvic ultrasound shows that girls have at least one ovarian follicle with a diameter >4mm, and breast development is at least at Tanner stage II; boys have a testicular volume ≥ 4 ml (measured with Prader orchidometer).

3. GnRH stimulation test: LH peak value ≥ 5 IU/L (chemiluminescence method), with an LH peak/FSH peak ratio ≥ 0.6.

4. Bone age (BA) exceeds chronological age (CA) by 1 year or more (based on bone age assessment during the screening period at this center).

5. Accelerated linear growth, with an annual growth rate higher than that of healthy children of the same age.

6. No prior treatment with gonadotropin-releasing hormone agonists.

7. Body weight of at least 20 kg.

Exclusion Criteria

1.Target Diseases:

1. Secondary central precocious puberty: This includes central nervous system abnormalities (tumors or space-occupying lesions, acquired injuries, congenital developmental abnormalities, etc.) and other diseases (congenital adrenal hyperplasia, familial male-limited precocious puberty, McCune-Albright syndrome, etc.).

2. Slow-progressing central precocious puberty: Some children show signs of sexual development before the defined age (7-8 years), but the progression of sexual development and bone age is slow, and linear growth remains within the corresponding percentiles.

2.Treatment History, Medical History, and Concomitant Medical Conditions:

3. Known hypersensitivity to any investigational substance or related compounds.

4. Any chronic disease or treatment deemed by the investigator to potentially interfere with growth or other study endpoints [including but not limited to: long-term glucocorticoid use (excluding short-term topical use), renal failure, diabetes, moderate to severe scoliosis].

5. Girls with a bone age over 12.5 years or menarche ≥ 1 year; boys with a bone age over 14 years (based on bone age assessment during the screening period at this center).

6. Congenital long QT syndrome/12-lead ECG at screening showing QTc ≥ 500 ms corrected by Bazett's formula, excluding other factors causing prolonged QT interval on ECG/12-lead ECG at screening showing QTc between 480 and 499 ms accompanied by unexplained syncope, with no other factors causing prolonged QT interval and no pathogenic mutations.

7. BMI ≥ 95th percentile (same age and gender).

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

OTHER

Sponsor Role: lead

Responsible Party

Zhe Meng,MD

Associate chief physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhe Meng, master

Role: STUDY_DIRECTOR

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Liyang Liang, PhD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Locations

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Siqi Huang, master

Role: CONTACT

huangsq23@mail.sysu.edu.cn

+8615692418384

Facility Contacts

Siqi Huang, master

Role: primary

huangsq23@mail.sysu.edu.cn

+8615692418384

References

Subspecialty Group of Endocrinologic, Hereditary and Metabolic Diseases, the Society of Pediatrics, Chinese Medical Association; Editorial Board, Chinese Journal of Pediatrics. [Expert consensus on the diagnosis and treatment of central precocious puberty(2022)]. Zhonghua Er Ke Za Zhi. 2023 Jan 2;61(1):16-22. doi: 10.3760/cma.j.cn112140-20220802-00693. Chinese.

Reference Type: RESULT

PMID: 36594116 (View on PubMed)

Cheuiche AV, da Silveira LG, de Paula LCP, Lucena IRS, Silveiro SP. Diagnosis and management of precocious sexual maturation: an updated review. Eur J Pediatr. 2021 Oct;180(10):3073-3087. doi: 10.1007/s00431-021-04022-1. Epub 2021 Mar 21.

Reference Type: RESULT

PMID: 33745030 (View on PubMed)

Luo X, Zhang C, Yang Y, Xu X, Cheng X, Wei H, Wang L, Huang F, Shi X, Cabri P. Efficacy and Safety of Triptorelin 3-Month Formulation in Chinese Children with Central Precocious Puberty: A Phase 3, Open-Label, Single-Arm Study. Adv Ther. 2023 Oct;40(10):4574-4588. doi: 10.1007/s12325-023-02617-8. Epub 2023 Aug 16.

Reference Type: RESULT

PMID: 37584898 (View on PubMed)

Bangalore Krishna K, Fuqua JS, Rogol AD, Klein KO, Popovic J, Houk CP, Charmandari E, Lee PA, Freire AV, Ropelato MG, Yazid Jalaludin M, Mbogo J, Kanaka-Gantenbein C, Luo X, Eugster EA, Klein KO, Vogiatzi MG, Reifschneider K, Bamba V, Garcia Rudaz C, Kaplowitz P, Backeljauw P, Allen DB, Palmert MR, Harrington J, Guerra-Junior G, Stanley T, Torres Tamayo M, Miranda Lora AL, Bajpai A, Silverman LA, Miller BS, Dayal A, Horikawa R, Oberfield S, Rogol AD, Tajima T, Popovic J, Witchel SF, Rosenthal SM, Finlayson C, Hannema SE, Castilla-Peon MF, Mericq V, Medina Bravo PG. Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium. Horm Res Paediatr. 2019;91(6):357-372. doi: 10.1159/000501336. Epub 2019 Jul 18.

Reference Type: RESULT

PMID: 31319416 (View on PubMed)

Durand A, Tauber M, Patel B, Dutailly P. Meta-Analysis of Paediatric Patients with Central Precocious Puberty Treated with Intramuscular Triptorelin 11.25 mg 3-Month Prolonged-Release Formulation . Horm Res Paediatr. 2017;87(4):224-232. doi: 10.1159/000456545. Epub 2017 Mar 23.

Reference Type: RESULT

PMID: 28334719 (View on PubMed)

Chung LY, Kang E, Nam HK, Rhie YJ, Lee KH. Efficacy of Triptorelin 3-Month Depot Compared to 1-Month Depot for the Treatment of Korean Girls with Central Precocious Puberty in Single Tertiary Center. J Korean Med Sci. 2021 Aug 30;36(34):e219. doi: 10.3346/jkms.2021.36.e219.

Reference Type: RESULT

PMID: 34463062 (View on PubMed)

Carel JC, Blumberg J, Seymour C, Adamsbaum C, Lahlou N; Triptorelin 3-month CPP Study Group. Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty. Eur J Endocrinol. 2006 Jan;154(1):119-24. doi: 10.1530/eje.1.02056.

Reference Type: RESULT

PMID: 16382000 (View on PubMed)

Huang S, Zhang L, Gao C, Ou H, Hou L, Liu Z, Wang D, Xu Y, Liang L, Meng Z. Efficacy and safety of leuprorelin 3-month depot (11.25 mg) for idiopathic central precocious puberty treatment of Chinese girls: a single-center retrospective study. J Pediatr Endocrinol Metab. 2023 Nov 20;37(1):15-20. doi: 10.1515/jpem-2023-0410. Print 2024 Jan 29.

Reference Type: RESULT

PMID: 37975727 (View on PubMed)

Ramos CO, Canton APM, Seraphim CE, Faria AG, Tinano FR, Mendonca BB, Latronico AC, Brito VN. Anthropometric, metabolic, and reproductive outcomes of patients with central precocious puberty treated with leuprorelin acetate 3-month depot (11.25 mg). J Pediatr Endocrinol Metab. 2021 Jul 23;34(11):1371-1377. doi: 10.1515/jpem-2021-0142. Print 2021 Nov 25.

Reference Type: RESULT

PMID: 34298591 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

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Other Identifiers

3-month TP vs 1-month TP

Identifier Type: -

Identifier Source: org_study_id