A Study to Evaluate Leuprolide Acetate 45 mg 6-Month Formulation in Children With Central Precocious Puberty (CPP)

Study Overview
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Brief Summary
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The primary objective of the study is to assess the safety and efficacy of a leuprolide acetate (LA) 45 mg 6-month depot formulation for the treatment of CPP in children who are either naïve to treatment with a gonadotropin-releasing hormone agonist (GnRHa) or who have been previously treated with a GnRHa.

Official Title
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A Phase 3, Multicenter, Open-Label, Two-Part Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Leuprolide Acetate 45 mg 6-Month Depot Formulation in Children With Central Precocious Puberty (CPP)

Conditions
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Central Precocious Puberty (CPP)

Intervention / Treatment
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* Drug: Leuprolide Acetate (LA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with CPP who are naïve to treatment with a gonadotropin-releasing hormone agonist (GnRHa) (females 2 - 8 years of age, or males 2 - 9 years of age) or who have been on standard GnRHa therapy for at least 6 months (females 2 - 10 years of age, or males 2 - 11 years of age). No history of clinically significant medical conditions or any other reason that the investigator determines would make the participant an unsuitable candidate to receive study drug.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 11 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: Leuprolide Acetate (LA)<br>Participants received leuprolide acetate (LA) 45 mg every 6 months administered as an intramuscular injection for up to 144 weeks. | Drug: Leuprolide Acetate (LA)<br>* Administered intramuscularly as an injection<br>* Other names: Lupron Depot;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Suppression of Peak Gonadotropin-releasing Hormone Agonist (GnRHa)-Stimulated Luteinizing Hormone (LH) to Less Than 4 mlU/mL at Week 24 | Suppression of GnRHa-stimulated luteinizing hormone (LH) was measured using a peak GnRHa stimulation test, performed using subcutaneous injection with an aqueous formulation of leuprolide acetate at 20 µg/kg. Peak stimulated LH was calculated by taking the maximum LH concentrations measured from blood samples taken at 30 or 60 min following the GnRHa stimulation test. Suppression of GnRHa-stimulated luteinizing hormone is defined as peak stimulated LH less than 4 mIU/mL. | Week 24 (prior to the Week 24 dose); samples for LH measurement were taken 30 and 60 minutes after the stimulation test injection. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Percentage of Participants With Suppression of Peak GnRHa-stimulated LH to Less Than 4 mlU/mL at Weeks 12, 20, 44, and 48 | Suppression of GnRHa-stimulated luteinizing hormone (LH) was measured using a peak GnRHa stimulation test, performed using subcutaneous injection with an aqueous formulation of leuprolide acetate at 20 µg/kg. Peak stimulated LH was calculated by taking the maximum LH concentrations measured from blood samples taken at 30 or 60 min following the GnRHa stimulation test. Suppression of GnRHa-stimulated luteinizing hormone is defined as peak stimulated LH less than 4 mIU/mL. | Weeks 12, 20, 44, and 48 (prior to Week 48 dose); samples for LH measurement were taken 30 and 60 minutes after the stimulation test injection. | 
| Part 1: Percentage of Female Participants With Suppression of Basal Estradiol to < 20 pg/mL at Weeks 12, 20, 24, 44, and 48 | Estradiol concentrations were measured from blood samples taken at each study visit prior to stimulation testing (and prior to study drug administration at Weeks 24 and 48). | Weeks 12, 20, 24, 44, and 48 | 
| Part 1: Percentage of Male Participants With Suppression of Basal Testosterone to < 30 ng/dL at Weeks 12, 20, 24, 44, and 48 | Testosterone concentrations were measured from blood samples taken at each study visit prior to stimulation testing (and prior to study drug administration for Weeks 24 and 48). | Weeks 12, 20, 24, 44, and 48 | 
| Part 1: Percentage of Participants With Suppression of the Physical Signs of Puberty | Breast development in females and testicular volume or genital development in males was assessed using modified Tanner staging, on a scale from Stage 1 (prepubertal) to Stage 5 (adult characteristics). Females: Suppression is defined as regression or no progression of breast development according to modified Tanner staging. Males: Suppression is defined as regression or no progression in testicular volume and genital staging according to modified Tanner staging. | Weeks 24 and 48 | 
| Part 1: Change From Baseline in Incremental Growth Rate | Growth rate (height in centimeter/year) was calculated both prior to treatment in the study and during the study. For Baseline calculation a historical measurement of height at least 6 months prior to Screening and the Screening value was used. | Baseline and Weeks 4, 12, 20, 24, 44, and 48 | 
| Part 1: Ratio of Change From Baseline in Bone Age to Change From Baseline in Chronological Age | Bone age was assessed from radiographs of the hand and wrist by a central imaging vendor using the BoneXpert automated system. A ratio less than 1 indicates less advancement of bone age compared to chronological age. | Baseline and Weeks 24 and 48 | 
| Part 2: Percentage of Participants With Maintenance of Suppression of GnRHa-stimulated LH (< 4 mlU/mL) |  | Weeks 72, 96, 120, and 144 | 
| Part 2: Percentage of Female Participants With Maintenance of Suppression of Basal Estradiol to < 20 pg/mL |  | Weeks 72, 96, 120, and 144 | 
| Part 2: Percentage of Male Participants With Maintenance of Suppression of Testosterone to < 30 ng/dL | Male participants with maintenance of suppression of testosterone to < 30 ng/dL are assessed | Weeks 72, 96, 120, and 144 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central Precocious Puberty (CPP), Leuprolide Acetate (LA)