Back to resultsStudy of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty
Primary Purpose
Precocious Puberty, Central
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Leuprolide Acetate 45 mg
Sponsored by
About this trial
This is an interventional treatment trial for Precocious Puberty, Central
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- University of California, San Diego
- Joe DiMaggio Children's Hospital
- Nemours Children's Clinic
- Nemours Children's Hospital
- Riley Hospital for Children at Indiana University Health
- University of Minnesota
- Cincinnati Children's Hospital Medical Center, Endocrine
- University of Oklahoma College of Medicine
- Seattle Children's
- MultiCare Institute for Research and Innovation
- Hospital de Ninos
- University of Calgary, Alberta Children's Hospital
- McGill University Health Centre
- CHU de Quebec-Universite Laval
- Pontificia Universidad Catolica de Chile
- Instituto de Investigaciones Materno Infantil (IDIMI)
- Hospital Regional de Antofagasta Leonardo Guzman
- Hospital Unversitario "Dr. Jose Eleuterio Gonzalez"
- Instituto de Investigaciones Aplicadas a la Neurociencia, A.C.
- The Liggins Institute, University of Auckland
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Assigned Intervention
Arm Description
Leuprolide acetate 45 mg will be administered as a subcutaneous injection at 6-month intervals for the 12 month study period.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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].
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.
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).
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02452931
Brief Title
Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
August 31, 2015 (Actual)
Primary Completion Date
September 5, 2018 (Actual)
Study Completion Date
September 5, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tolmar Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Precocious Puberty, Central
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Assigned Intervention
Arm Type
Experimental
Arm Description
Leuprolide acetate 45 mg will be administered as a subcutaneous injection at 6-month intervals for the 12 month study period.
Intervention Type
Drug
Intervention Name(s)
Leuprolide Acetate 45 mg
Intervention Description
Subcutaneous injection
Primary Outcome Measure Information:
Title
Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months.
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels.
Description
Percentage of subjects with suppressed serum LH concentrations(<4 IU/L) 30 minutes post GnRHa stimulation test at all assessed timepoints.
Time Frame
Week 12, Week 24, Week 36, and Week 48
Title
Changes in Height Velocity (Growth Rate)
Description
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].
Time Frame
Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Title
Bone Age Ratio to Chronological Age at Time of Measurement
Description
Bone Age Ratio to Chronological Age at Time of Measurement is bone age/age at bone age assessment.
Time Frame
Week 24 and Week 48
Title
Percent Change From Baseline in Height
Description
The percent change from baseline in height at each available post-baseline measurement. Percent change is defined as (((change from Baseline)/(Baseline)) x 100).
Time Frame
Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Title
Tanner Scores: Boys - Development of External Genitalia
Description
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.
Time Frame
Baseline, Week 12, Week 24, Week 36, and Week 48
Title
Tanner Scores: Boys - Development of External Genitalia (Change From Baseline)
Description
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.
Time Frame
Week 12, Week 24, Week 36, and Week 48
Title
Tanner Scores: Boys and Girls - Pubic Hair
Description
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.
Time Frame
Baseline, Week 12, Week 24, Week 36, and Week 48
Title
Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline)
Description
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.
Time Frame
Week 12, Week 24, Week 36, and Week 48
Title
Tanner Scores: Girls - Breast Development
Description
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.
Time Frame
Baseline, Week 12, Week 24, Week 36, and Week 48
Title
Tanner Scores: Girls - Breast Development (Change From Baseline)
Description
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.
Time Frame
Week 12, Week 24, Week 36, and Week 48
Other Pre-specified Outcome Measures:
Title
Height
Description
Height at each available measurement point. Baseline is defined as the last non-missing height measurement collected prior to or on the date of first injection.
Time Frame
Screening, Baseline, Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Title
Bone Age
Description
Bone Age at each available measurement point.
Time Frame
Baseline, Week 24, and Week 48
Title
Bone Age Progression
Description
Bone age progression at each available post-baseline measurement point. Bone age progression is defined as (((change from baseline)/(baseline)) x 100), which is percent change from baseline.
Time Frame
Week 24 and Week 48
Title
Bone Age Ratio to Chronological Age at Time of Measurement (Percent Change From Baseline)
Description
Bone Age Ratio to Chronological Age at Time of Measurement is bone age/age at bone age assessment.
Time Frame
Week 24 and Week 48
Title
Bone Age Ratio to Chronological Age at Start of Study (Percent Change From Baseline)
Description
Bone age advancement was evaluated relative to chronological age at each given measurement point. Percent change from baseline is: 100 x (the change from baseline value at the post-baseline visit / baseline value).
Time Frame
Week 24 and Week 48
Title
Bone Age Ratio to Chronological Age at Start of Study
Description
Bone age advancement was evaluated relative to chronological age at each given measurement point. Bone Age Ratio to Chronological Age at Start of Study is bone age/age at first injection.
Time Frame
Baseline, Week 24, and Week 48
Title
GnRH Antagonist Evaluation
Description
GnRH Antagonist Evaluation occurred for the two week period following each treatment and at each visit to assess flare symptoms. The percent of subjects who affirm (or whose parent/guardian affirms) each symptom domain in the global interview.
Time Frame
Week 2, Week 4, Week 12, Week 20, Week 24, Week 26, Week 36, Week 44, and Week 48
Title
Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels.
Description
The percentage of subjects with FSH, estradiol and testosterone suppression to prepubertal levels (FSH < 2.5 mIU/mL, estradiol < 20 pg/mL and testosterone < 28.4 ng/dL) at each available time point.
Time Frame
Week 12, Week 24, Week 36, and Week 48
Title
Changes in the Ratio of LH/FSH
Description
Changes in ratio of LH/FSH at each time point from Screening to End of Study
Time Frame
Screening (Pre&Post GnRHa Stim Test), Baseline (0,1,4,6 hours Post-Injection), Week 4, Week 12 (Pre&Post GnRHa Stim Test), Week 20, Week 24 (Pre&Post GnRHa Stim Test), Week 36 (Pre&Post GnRHa Stim Test), Week 44, and Week 48 (Pre&Post GnRHa Stim Test)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
9 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peggy Schorr
Organizational Affiliation
orphan reach USA, LLC
Official's Role
Study Director
Facility Information:
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Joe DiMaggio Children's Hospital
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Nemours Children's Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Nemours Children's Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Riley Hospital for Children at Indiana University Health
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55414
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center, Endocrine
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
University of Oklahoma College of Medicine
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74135
Country
United States
Facility Name
Seattle Children's
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
MultiCare Institute for Research and Innovation
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Hospital de Ninos
City
Buenos Aires
ZIP/Postal Code
C1425EFD
Country
Argentina
Facility Name
University of Calgary, Alberta Children's Hospital
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3B 6A8
Country
Canada
Facility Name
McGill University Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
CHU de Quebec-Universite Laval
City
Quebec
ZIP/Postal Code
G1V 4G2
Country
Canada
Facility Name
Pontificia Universidad Catolica de Chile
City
Santiago
State/Province
Metropolitana
ZIP/Postal Code
8330074
Country
Chile
Facility Name
Instituto de Investigaciones Materno Infantil (IDIMI)
City
Santiago
State/Province
Metropolitana
ZIP/Postal Code
8360160
Country
Chile
Facility Name
Hospital Regional de Antofagasta Leonardo Guzman
City
Antofagasta
State/Province
Second Region
ZIP/Postal Code
1270001
Country
Chile
Facility Name
Hospital Unversitario "Dr. Jose Eleuterio Gonzalez"
City
Monterrey
State/Province
Nuevo Leon
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Instituto de Investigaciones Aplicadas a la Neurociencia, A.C.
City
Durango
ZIP/Postal Code
34000
Country
Mexico
Facility Name
The Liggins Institute, University of Auckland
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
12. IPD Sharing Statement
Citations:
PubMed Identifier
32738042
Citation
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. Erratum In: J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2842.
Results Reference
derived
Learn more about this trial
Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty
We'll reach out to this number within 24 hrs