Central Precocious PubertyPhase 3NCT00779103
Histrelin Subcutaneous Implant in Children With Central Precocious Puberty
A Phase 3 study testing Histrelin Subcutaneous Implant in people with Central Precocious Puberty, run by Endo USA Inc., a Keenova Therapeutics Company.
Trial summary
The purpose of this study is to follow and collect additional medical and developmental information on children after histrelin subcutaneous implant therapy is discontinued. Read more about this study
- Who is it for?
- Ages 2 to 10 years
- Conditions the study is for
- Central Precocious Puberty
- What is being tested?
- Histrelin Subcutaneous Implant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- No sites listed yet
- Study dates
- Sep 2004to Apr 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
About this study
Official title: Phase III, Open-Label Study to Evaluate Efficacy and Safety of Histrelin Subdermal Implant in Children With Central Precocious Puberty
The purpose of this study is to follow and collect additional medical and developmental information on children after histrelin subcutaneous implant therapy is discontinued.
Read the detailed description
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.
- Conditions
- Central Precocious Puberty
- Being tested
- Histrelin Subcutaneous Implant
- Keywords
- puberty, precocious puberty, early puberty, early onset puberty, histrelin, histrelin subcutaneous implant, implant therapy
- Medical subject headings
- Puberty, Precocious
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Histrelin Subcutaneous ImplantDrug
Also called Supprelin LA, implant therapy, histrelin implant
histrelin subcutaneous 50 mg implant
| Study group | Role | What they receive |
|---|---|---|
| Histrelin Subcutaneous Implant (50 mg) | Experimental | Subcutaneous implant designed to deliver histrelin continously for 12 months. Receives: Drug: Histrelin Subcutaneous Implant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline - 6 Months Post Last Implant
Secondary outcomes (8)
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).
Measured: 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).
Measured: Baseline - 12 Months Post Last Implant
DHEA Sulfate
DHEA=Dehydroepiandrosterone
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 - Month 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2008 (estimated)
- Study startSep 2004
- Primary completionAug 2011
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Central Precocious PubertyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Erica A Eugster, MD, Principal investigator, Indiana University School of Medicine, 705 Riley Hosp Dr, Rm 5960 Indianapolis, IN 46202
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00779103
- Sponsor's protocol ID
- EN3326-300Former03-CPP-HIS-300
- Status last verified
- Oct 2020
- First submitted
- 22 Oct 2008
- Last updated
- 8 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Silverman LA, Neely EK, Kletter GB, Lewis K, Chitra S, Terleckyj O, Eugster EA. Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial. J Clin Endocrinol Metab. 2015 Jun;100(6):2354-63. doi: 10.1210/jc.2014-3031. Epub 2015 Mar 24.
PubMed 25803268Neely EK, Silverman LA, Geffner ME, Danoff TM, Gould E, Thornton PS. Random unstimulated pediatric luteinizing hormone levels are not reliable in the assessment of pubertal suppression during histrelin implant therapy. Int J Pediatr Endocrinol. 2013 Dec 2;2013(1):20. doi: 10.1186/1687-9856-2013-20.
PubMed 24295437
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III, Open-Label Study to Evaluate Efficacy and Safety of Histrelin Subdermal Implant in Children With Central Precocious Puberty
- ClinicalTrials.gov ID
- NCT00779103
- Acronym / sponsor ID
- EN3326-300Former03-CPP-HIS-300
- Conditions
- Central Precocious Puberty
- Keywords
- puberty, precocious puberty, early puberty, early onset puberty, histrelin, histrelin subcutaneous implant, implant therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics CompanyIndustry (pharma, biotech, devices)
- Study start
- Sep 2004
- Primary completion
- Aug 2011 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 24 Oct 2008 (estimated)
- Results
- Posted 8 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Histrelin Subcutaneous Implant (50 mg) | Experimental | Drug: Histrelin Subcutaneous ImplantSubcutaneous implant designed to deliver histrelin continously for 12 months. |
Who may qualify
- Ages
- 2 to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Histrelin Subcutaneous ImplantAlso: Supprelin LA, implant therapy, histrelin implanthistrelin subcutaneous 50 mg implant | Drug | Histrelin Subcutaneous Implant (50 mg) |
Primary outcome
Luteinizing Hormone (LH)
Time frame: Baseline - 6 Months Post Last Implant
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).
8 secondary outcomes
Follicle Stimulating Hormone (FSH)
Time frame: Baseline - 6 Month Post Last Implant
Testosterone
Time frame: Baseline - 12 Months Post Last Implant
DHEA Sulfate
Time frame: Baseline - 36 Months Post Last Implant
Estradiol (MS)
Time frame: Month 36 - 36 Months Post Last Implant
Estradiol (RIA)
Time frame: Baseline - Month 24
Average Number of Implants Received
Time frame: 12 months
Average Mean Implant Duration by Subject
Time frame: 12 Months
Summary of EN3326 Implantation and Explantations
Time frame: Day 1 - Month 60
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25803268Silverman LA, Neely EK, Kletter GB, Lewis K, Chitra S, Terleckyj O, Eugster EA. Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial. J Clin Endocrinol Metab. 2015 Jun;100(6):2354-63. doi: 10.1210/jc.2014-3031. Epub 2015 Mar 24.
- Derived from this study: PubMed 24295437Neely EK, Silverman LA, Geffner ME, Danoff TM, Gould E, Thornton PS. Random unstimulated pediatric luteinizing hormone levels are not reliable in the assessment of pubertal suppression during histrelin implant therapy. Int J Pediatr Endocrinol. 2013 Dec 2;2013(1):20. doi: 10.1186/1687-9856-2013-20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erica A Eugster, MD principal investigator
Indiana University School of Medicine, 705 Riley Hosp Dr, Rm 5960 Indianapolis, IN 46202
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Histrelin Subcutaneous Implant in people with Central Precocious Puberty, run by Endo USA Inc., a Keenova Therapeutics Company.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Luteinizing Hormone (LH) (time frame: Baseline - 6 Months Post Last Implant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00779103, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2021.