Precocious Puberty, CentralPhase 3NCT02452931
Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty
A Phase 3 study testing Leuprolide Acetate 45 mg in people with Precocious Puberty, Central, run by Tolmar Inc. at 20 sites in 6 countries.
Trial summary
This study determines the effectiveness of leuprolide acetate 45 mg for injectable suspension for treatment of children with Central Precocious Puberty. Read more about this study
- Who is it for?
- Ages 2 to 9 years
- Conditions the study is for
- Precocious Puberty, Central
- What is being tested?
- Leuprolide Acetate 45 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 20 sitesin 6 countries
- Study dates
- 31 Aug 2015to 5 Sep 2018
- 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 9 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Females age 2 to 8 years (inclusive) or males age 2 to 9 years (inclusive)
- Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have not received prior GnRH agonist treatment for CPP
- Pubertal-type LH response following an abbreviated GnRHa stimulation test before treatment initiation
- Clinical evidence of puberty, defined as Tanner stage ≥ 2 for breast development in females or testicular volume ≥ 4 mL in males
- Difference between bone age (Greulich and Pyle method) and chronological age ≥ 1 year
Who cannot join
- Gonadotropin-independent (peripheral) precocious puberty
- Prior or current GnRH treatment for CPP
- Prior or current therapy with medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1)
- Diagnosis of short stature (ie, 2.25 standard deviations (SD) below the mean height for age)
- Known history of seizures, epilepsy, and/or central nervous system disorders that may be associated with seizures or convulsions
- Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study
Trial locations and contacts
20 sites in 6 countries.
20 sites in 6 countries
United States10 sites
Cincinnati Children's Hospital Medical Center, Endocrine
Cincinnati, Ohio, 45229
Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202
Nemours Children's Clinic
Jacksonville, Florida, 32207
University of Minnesota
Minneapolis, Minnesota, 55414
Nemours Children's Hospital
Orlando, Florida, 32827
University of California, San Diego
San Diego, California, 92123
Seattle Children's
Seattle, Washington, 98105
MultiCare Institute for Research and Innovation
Tacoma, Washington, 98405
University of Oklahoma College of Medicine
Tulsa, Oklahoma, 74135
Canada3 sites
University of Calgary, Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
McGill University Health Centre
Montreal, Quebec, H4A 3J1
CHU de Quebec-Universite Laval
Québec, G1V 4G2
Chile3 sites
Hospital Regional de Antofagasta Leonardo Guzman
Antofagasta, Second Region, 1270001
Pontificia Universidad Catolica de Chile
Santiago, Santiago Metropolitan, 8330074
Instituto de Investigaciones Materno Infantil (IDIMI)
Santiago, Santiago Metropolitan, 8360160
Mexico2 sites
Instituto de Investigaciones Aplicadas a la Neurociencia, A.C.
Durango, 34000
Hospital Unversitario "Dr. Jose Eleuterio Gonzalez"
Monterrey, Nuevo León, 64460
New Zealand1 site
The Liggins Institute, University of Auckland
Auckland, 1023
About this study
Official title: An Open-label, Single Arm, Multicenter Study on the Efficacy, Safety, and Pharmacokinetics of Leuprolide Acetate 45 mg for Injectable Suspension Controlled Release in Subjects With Central (Gonadotropin-Dependent) Precocious Puberty
This study determines the effectiveness of leuprolide acetate 45 mg for injectable suspension for treatment of children with Central Precocious Puberty.
Read the detailed description
Leuprolide acetate is a GnRH agonist that inhibits pituitary gonadotropin secretion by binding to the GnRH receptors and blocking downstream hormone synthesis. The steady decrease in hormone synthesis (LH and FSH) leads to a suppression of testicular and ovarian steroidogenesis. In children with CPP, this steady decrease in hormone synthesis disrupts the progression of puberty.
- Conditions
- Precocious Puberty, Central
- Being tested
- Leuprolide Acetate 45 mg
- Medical subject headings
- Puberty, Precocious
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Leuprolide Acetate 45 mgDrug
Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Assigned Intervention | Experimental | Leuprolide acetate 45 mg will be administered as a subcutaneous injection at 6-month intervals for the 12 month study period. Receives: Drug: Leuprolide Acetate 45 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months.
Luteinizing Hormone (LH) suppression is defined as peak-stimulated LH <4 IU/L. Peak stimulated LH refers to the maximum LH concentration measured 30 minutes after a gonadotropin-releasing hormone agonst (GnRHa) stimulation test.
Measured: 6 months
Secondary outcomes (10)
Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels.
Percentage of subjects with suppressed serum LH concentrations(<4 IU/L) 30 minutes post GnRHa stimulation test at all assessed timepoints.
Measured: Week 12, Week 24, Week 36, and Week 48
Changes in Height Velocity (Growth Rate)
Changes in height velocity (growth rate) at all study timepoints after Screening to end of study. Growth velocity is defined for each visit as change from baseline / [(number of weeks since baseline)/52]. Week 48: Change from Week 24 growth velocity is defined as change from week 24 to week 48 / [(number of weeks since week 24)/52].
Measured: Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Bone Age Ratio to Chronological Age at Time of Measurement
Bone Age Ratio to Chronological Age at Time of Measurement is bone age/age at bone age assessment.
Measured: Week 24 and Week 48
Percent Change From Baseline in Height
The percent change from baseline in height at each available post-baseline measurement. Percent change is defined as (((change from Baseline)/(Baseline)) x 100).
Measured: Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Tanner Scores: Boys - Development of External Genitalia
Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Measured: Baseline, Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Boys - Development of External Genitalia (Change From Baseline)
Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Measured: Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Boys and Girls - Pubic Hair
Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Measured: Baseline, Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline)
Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Measured: Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Girls - Breast Development
Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Measured: Baseline, Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Girls - Breast Development (Change From Baseline)
Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Measured: Week 12, Week 24, Week 36, and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2015 (estimated)
- Study start31 Aug 2015
- Primary completion5 Sep 2018
- Study completion5 Sep 2018
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 (1)Papers the sponsor has linked to this study.
- Other trials for Precocious Puberty, CentralStudies 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
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tolmar Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Peggy Schorr, Study director, orphan reach USA, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02452931
- Sponsor's protocol ID
- TOL2581A
- Status last verified
- May 2020
- First submitted
- 5 May 2015
- Last updated
- 2 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Klein KO, Freire A, Gryngarten MG, Kletter GB, Benson M, Miller BS, Dajani TS, Eugster EA, Mauras N. Phase 3 Trial of a Small-volume Subcutaneous 6-Month Duration Leuprolide Acetate Treatment for Central Precocious Puberty. J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3660-71. doi: 10.1210/clinem/dgaa479.
PubMed 32738042
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single Arm, Multicenter Study on the Efficacy, Safety, and Pharmacokinetics of Leuprolide Acetate 45 mg for Injectable Suspension Controlled Release in Subjects With Central (Gonadotropin-Dependent) Precocious Puberty
- ClinicalTrials.gov ID
- NCT02452931
- Acronym / sponsor ID
- TOL2581A
- Conditions
- Precocious Puberty, Central
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Tolmar Inc.Industry (pharma, biotech, devices)
- Study start
- 31 Aug 2015 (actual)
- Primary completion
- 5 Sep 2018 (actual)
- Study completion
- 5 Sep 2018 (actual)
- First posted
- 25 May 2015 (estimated)
- Results
- Posted 20 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study determines the effectiveness of leuprolide acetate 45 mg for injectable suspension for treatment of children with Central Precocious Puberty.
Detailed description
Leuprolide acetate is a GnRH agonist that inhibits pituitary gonadotropin secretion by binding to the GnRH receptors and blocking downstream hormone synthesis. The steady decrease in hormone synthesis (LH and FSH) leads to a suppression of testicular and ovarian steroidogenesis. In children with CPP, this steady decrease in hormone synthesis disrupts the progression of puberty.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Assigned Intervention | Experimental | Drug: Leuprolide Acetate 45 mgLeuprolide acetate 45 mg will be administered as a subcutaneous injection at 6-month intervals for the 12 month study period. |
Who may qualify
- Ages
- 2 to 9 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Females age 2 to 8 years (inclusive) or males age 2 to 9 years (inclusive)
- Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have not received prior GnRH agonist treatment for CPP
- Pubertal-type LH response following an abbreviated GnRHa stimulation test before treatment initiation
- Clinical evidence of puberty, defined as Tanner stage ≥ 2 for breast development in females or testicular volume ≥ 4 mL in males
- Difference between bone age (Greulich and Pyle method) and chronological age ≥ 1 year
Key exclusion criteria (6 listed)
- Gonadotropin-independent (peripheral) precocious puberty
- Prior or current GnRH treatment for CPP
- Prior or current therapy with medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1)
- Diagnosis of short stature (ie, 2.25 standard deviations (SD) below the mean height for age)
- Known history of seizures, epilepsy, and/or central nervous system disorders that may be associated with seizures or convulsions
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 |
|---|---|---|
| Leuprolide Acetate 45 mgSubcutaneous injection | Drug | Assigned Intervention |
Primary outcome
Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months.
Time frame: 6 months
Luteinizing Hormone (LH) suppression is defined as peak-stimulated LH <4 IU/L. Peak stimulated LH refers to the maximum LH concentration measured 30 minutes after a gonadotropin-releasing hormone agonst (GnRHa) stimulation test.
10 secondary outcomes
Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels.
Time frame: Week 12, Week 24, Week 36, and Week 48
Changes in Height Velocity (Growth Rate)
Time frame: Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Bone Age Ratio to Chronological Age at Time of Measurement
Time frame: Week 24 and Week 48
Percent Change From Baseline in Height
Time frame: Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Tanner Scores: Boys - Development of External Genitalia
Time frame: Baseline, Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Boys - Development of External Genitalia (Change From Baseline)
Time frame: Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Boys and Girls - Pubic Hair
Time frame: Baseline, Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline)
Time frame: Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Girls - Breast Development
Time frame: Baseline, Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Girls - Breast Development (Change From Baseline)
Time frame: Week 12, Week 24, Week 36, and Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32738042Klein KO, Freire A, Gryngarten MG, Kletter GB, Benson M, Miller BS, Dajani TS, Eugster EA, Mauras N. Phase 3 Trial of a Small-volume Subcutaneous 6-Month Duration Leuprolide Acetate Treatment for Central Precocious Puberty. J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3660-71. doi: 10.1210/clinem/dgaa479.
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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.
Peggy Schorr study director
orphan reach USA, LLC
20 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Leuprolide Acetate 45 mg in people with Precocious Puberty, Central, run by Tolmar Inc. at 20 sites in 6 countries.
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 5 inclusion and 6 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 2 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada, Chile, Mexico, Argentina and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
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 20 May 2020). 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?
Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months. (time frame: 6 months). 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 NCT02452931, which also lists 1 linked publication.
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 2 Jun 2020.