Histrelin Subcutaneous Implant in Children With Central Precocious Puberty

Study Overview
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Brief Summary
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The purpose of this study is to follow and collect additional medical and developmental information on children after histrelin subcutaneous implant therapy is discontinued.

Detailed Description
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Thirty-two (32) patients will receive a histrelin subdermal implant under the anesthesia deemed appropriate by the administering physician. Ten-twelve (10-12) sites will enroll 2-3 patients per site. It is anticipated that half the patients will be receiving GnRH analog treatment and the other half will be treatment naïve. All patients will undergo selective PK sampling post-implantation to assess histrelin profile. At 12 months, provided that the patient continues to meet the safety and efficacy parameters, the original implant will be removed and the patient can receive a new implant. At 13 months, patients who receive new implants will be evaluated at the study site and administratively transferred to the initial extension study. At Month 24), the implants inserted at Month 12 will be removed. At this time, patients who have completed the initial extension study and who wish to continue therapy with the histrelin implant will be eligible to receive a new (ie, third) implant and to enter an additional 12-month extended access phase at the discretion of the investigator. At Month 36, the implants inserted at Month 24 for the Extended Access Phase will be removed. At this time, patients who have completed the Extended Access Phase and who wish to continue therapy with the histrelin implant will be eligible to receive a new (ie, fourth) implant and to enter the Long Term Extended Access Phase (referred to as the Implant Treatment Phase) at the discretion of the investigator. The purpose of this phase is to provide patients with the opportunity to continue to receive a new implant at the end of each 12-month period until the patient no longer requires hormone suppression. Once implant therapy is discontinued, all patients are eligible to enter the Long Term Follow Up Phase (Post Implant Phase) of the study.

Official Title
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Phase III, Open-Label Study to Evaluate Efficacy and Safety of Histrelin Subdermal Implant in Children With Central Precocious Puberty

Conditions
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Central Precocious Puberty

Intervention / Treatment
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* Drug: Histrelin Subcutaneous Implant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-treated or treatment naive patients with gonadotropin-dependent precocious puberty Pre-treatment pubertal type response of LH to a stndard GnRH stimulation test before initiation of treatment Exclusion Criteria: Children who are less than 2 years of age at enrollment Children whose chronological age is greater than 8 years (naive) and 10 years (pre-treated) for girls or 9 years (naive) and 11 years (pre-treated) for boys at the onset of the study

Ages Eligible for Study
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Minimum Age: 2 Years
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: Histrelin Subcutaneous Implant (50 mg)<br>Subcutaneous implant designed to deliver histrelin continously for 12 months. | Drug: Histrelin Subcutaneous Implant<br>* histrelin subcutaneous 50 mg implant<br>* Other names: histrelin implant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Luteinizing Hormone (LH) | The suppression of gonadotropins (luteinizing hormone and follicle stimulating hormone) and gonadal sex steroids (estrogen in girls and testosterone in boys, respectively) on treatment.(LH suppression is defined as a peak LH < 4 mIU/mL following stimulation with the GnRH analog). | Baseline - 6 Months Post Last Implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Follicle Stimulating Hormone (FSH) | The suppression of gonadotropins (luteinizing hormone and follicle stimulating hormone) and gonadal sex steroids (estrogen in girls and testosterone in boys, respectively) on treatment.(LH suppression is defined as a peak LH < 4 mIU/mL following stimulation with the GnRH analog). | Baseline - 6 Month Post Last Implant | 
| Testosterone | Long-term treatment with histrelin acetate suppresses the LH response to GnRH causing LH levels to decrease to prepubertal levels within 1 month of treatment. As a result, serum concentrations of sex steroids (estrogen or testosterone) also decrease. Testosterone suppression is defined as serum testosterone < 30.0 ng/dL (0.8 nmol/L) in boys following the induction of suppression. One black female participant age 8.9 years old had a testosterone value of 11ng/dL at visit 4 (month 6). | Baseline - 12 Months Post Last Implant | 
| DHEA Sulfate | DHEA=Dehydroepiandrosterone | Baseline - 36 Months Post Last Implant | 
| Estradiol (MS) | Long-term treatment with histrelin acetate suppresses the LH response to GnRH causing LH levels to decrease to prepubertal levels within 1 month of treatment. As a result, serum concentrations of sex steroids (estrogen or testosterone) also decrease. Estradiol suppression is defined as serum estradiol in the assay specific range < 20 pg/mL (73 pmol/L) in girls following the induction of suppression. | Month 36 - 36 Months Post Last Implant | 
| Estradiol (RIA) | Long-term treatment with histrelin acetate suppresses the LH response to GnRH causing LH levels to decrease to prepubertal levels within 1 month of treatment. As a result, serum concentrations of sex steroids (estrogen or testosterone) also decrease. Estradiol suppression is defined as serum estradiol in the assay specific range < 20 pg/mL (73 pmol/L) in girls following the induction of suppression. | Baseline - Month 24 | 
| Average Number of Implants Received | There were 2 implants received that were not removed during the study and were excluded from this analysis due to unknown duration of treatment. | 12 months | 
| Average Mean Implant Duration by Subject | There were 2 implants received that were not removed during the study and were excluded from this analysis due to unknown duration of treatment. | 12 Months | 
| Summary of EN3326 Implantation and Explantations | Once the female participants reached 11 years of age and the male participants reached 12 years of age or the investigator determined that subjects no longer required hormone suppression, participants underwent final explantation and were eligible to continue into an optional Long Term Follow Up Phase (Post Implant Treatment Phase) for up to 5 years. The purpose of the optional Long Term Follow Up Phase was to collect additional medical and developmental information, such as onset of menses and final adult height after hormone suppression was discontinued. | Day 1 - Month 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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puberty, precocious puberty, early puberty, early onset puberty, histrelin, histrelin subcutaneous implant, implant therapy