Central Precocious Puberty
Conditions
Keywords
Drug Therapy
Brief summary
The main aim is to see how leuprolide works to treat central precocious puberty in children. Participants will receive an injection of leuprorelin acetate depot 11.25 mg every 12 weeks during 6 months and will visit their study clinic 6 times to complete some assessments.
Detailed description
The drug being tested in this study is called leuprorelin acetate depot 3M. Leuprorelin acetate depot 3M will be tested to treat children who have central precocious puberty. This study will look at the efficacy and safety of leuprorelin acetate depot 3M in the treatment of CPP. The study will enroll approximately 80 participants with CPP. Participants with a bodyweight of ≥ 20 kg will receive the recommended dose of leuprorelin acetate depot 3M in a 24 weeks Treatment Period followed by a 12 weeks Post-treatment follow-up period. Participants will be assigned to the following drug administration: • Leuprorelin Acetate Depot 3M 11.25 mg Participants will receive leuprorelin acetate depot 3M 11.25 mg as subcutaneous (SC) injection on Weeks 0, 12, and 24. The gonadotropin-releasing hormone agonist (GnRHa) stimulation, basal luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels will be tested pre-dose of every SC injection of the study drug or at premature termination. This multi-center trial will be conducted in China. The overall time to participate in this study is 38 weeks. Participants will make a follow-up visit to the site at approximately 12 weeks after the last dose of study treatment.
Interventions
DRUGLeuprorelin Acetate Depot 3M
Leuprorelin Acetate Depot 3M SC injections.
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 10 Years
Healthy volunteers
No
Inclusion criteria
1. Maximum age to participate is this study is up to 10 years (child). Early appearance of secondary sexual characteristics: Girls ≤8 years, Boys ≤9years 2. Body weight ≥20 kg 3. According to the National Consensus Statement in China (2015), CPP is diagnosed when secondary sexual characteristics appeared before the age of 8 years in girls and 9 years in boys, a peak LH level \>5.0 IU/L with LH/FSH \>0.6 in stimulating test; evidence of gonadal development by ultrasonography (multiple ovarian follicles ≥4 mm in any ovary or uterine enlargement in females or testicular volume ≥4 mL in males); advanced bone age (BA) ≥1 year; linear growth acceleration with higher growth velocity (GV) than normal children. BA is determined by Greulich and Pyle standards or TW3 standards at screening.
Exclusion criteria
1. The participant has received GnRHa treatment in a previous clinical study or as a therapeutic agent. 2. The participant has a history or clinical manifestations of significant adrenal or thyroid diseases or intracranial tumor OR has a history of malignant disease. 3. The participant has a history of hypersensitivity or allergies to leuprorelin, or related compounds including any excipients of the compound. 4. The participant has a diagnosis of peripheral precocious puberty.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Peak Luteinizing Hormone (LH) Suppression in Gonadotropin-Releasing Hormone (GnRH) Stimulation at Week 24 | Week 24 | The LH suppression was defined as LH peak value in GnRH stimulation ≤3.0 international unit per liter (IU/L). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Tanner Stage Regression or No Progression at Week 24 | Baseline and Week 24 | Tanner Stage was used to measure pubertal development. Tanner Stage was based on progression through 5-stages. The progression was defined as either breast/genitals or pubic hair score had increased score compared with baseline score. Otherwise, the status was classified as regression or no progression. Baseline is defined as the assessment prior to the first dose of study drug. |
| Concentrations of Basal Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) | Baseline, Weeks 24 and 36 | Plasma LH and FSH peak concentrations under GnRH stimulation were assessed. |
| Percentage of Participants With Decreased Ratio of Bone Age Over Chronological Age at Week 24 | Baseline and Week 24 | Bone age was determined by Greulich and Pyle standards or Tanner-Whitehouse 3 (TW3) standards. |
| Percentage of Participants With Decreased First Morning Voided (FMV) Urinary Gonadotropin (Gn) at Week 24 | Baseline and Week 24 | — |
| Number of Participants With Treatment-Emergent Adverse Events (TEAE) | From first dose of study drug up to 12 weeks post last dose or early termination Visit (ET) (up to approximately 36 weeks) | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAE is defined as an AE with an onset that occurs after receiving study drug. |
Countries
China
Contacts
STUDY_DIRECTORStudy Director
Takeda
Participant flow
Recruitment details
A total of 79 participants took part in the study at 5 investigative sites in China from 12 March 2023 to 10 March 2025.
Pre-assignment details
Participants with a diagnosis of central precocious puberty (CPP) received leuprorelin acetate depot 11.25 milligrams (mg).
Participants by arm
| Arm | Count |
|---|---|
| Leuprorelin Acetate Depot 3M 11.25 mg Participants with CPP having body weight ≥20 kg received the recommended dose of leuprorelin acetate depot 11.25 mg SC every 12 weeks based on the standard of 30～180 μg/kg/4 weeks for the 24-week Treatment Period. It was not recommended to exceed the dose above 180 μg/kg. | 79 |
| Total | 79 |
Baseline characteristics
| Characteristic | Leuprorelin Acetate Depot 3M 11.25 mg |
|---|---|
| Age, Continuous | 7.59 years STANDARD_DEVIATION 1.019 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 79 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 78 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 79 |
| other Total, other adverse events | 4 / 79 |
| serious Total, serious adverse events | 1 / 79 |
Outcome results
Primary
Percentage of Participants With Peak Luteinizing Hormone (LH) Suppression in Gonadotropin-Releasing Hormone (GnRH) Stimulation at Week 24
The LH suppression was defined as LH peak value in GnRH stimulation ≤3.0 international unit per liter (IU/L).
Time frame: Week 24
Population: The enrolled population set included all the eligible participants enrolled in this study, i.e., all participants enrolled in this study who met the inclusion criteria and did not meet any of the exclusion criteria, regardless of whether they received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Leuprorelin Acetate Depot 3M 11.25 mg | Percentage of Participants With Peak Luteinizing Hormone (LH) Suppression in Gonadotropin-Releasing Hormone (GnRH) Stimulation at Week 24 | 97.47 percentage of participants |
Secondary
Concentrations of Basal Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH)
Plasma LH and FSH peak concentrations under GnRH stimulation were assessed.
Time frame: Baseline, Weeks 24 and 36
Population: The enrolled population set included all the eligible participants enrolled in this study, i.e., all participants enrolled in this study who met the inclusion criteria and did not meet any of the exclusion criteria, regardless of whether they received the study drug. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprorelin Acetate Depot 3M 11.25 mg | Concentrations of Basal Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) | LH: Baseline | 1.224 IU/L | Standard Deviation 1.41 |
| Leuprorelin Acetate Depot 3M 11.25 mg | Concentrations of Basal Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) | LH: Week 24 | 0.454 IU/L | Standard Deviation 0.297 |
| Leuprorelin Acetate Depot 3M 11.25 mg | Concentrations of Basal Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) | LH: Week 36 | 0.458 IU/L | Standard Deviation 0.293 |
| Leuprorelin Acetate Depot 3M 11.25 mg | Concentrations of Basal Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) | FSH: Baseline | 3.213 IU/L | Standard Deviation 1.593 |
| Leuprorelin Acetate Depot 3M 11.25 mg | Concentrations of Basal Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) | FSH: Week 24 | 1.457 IU/L | Standard Deviation 0.686 |
| Leuprorelin Acetate Depot 3M 11.25 mg | Concentrations of Basal Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) | FSH: Week 36 | 1.569 IU/L | Standard Deviation 0.706 |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAE)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAE is defined as an AE with an onset that occurs after receiving study drug.
Time frame: From first dose of study drug up to 12 weeks post last dose or early termination Visit (ET) (up to approximately 36 weeks)
Population: The safety population set included all included participants who had been under treatment with leuprorelin or who were first prescribed leuprorelin, received at least one dose and completed one follow-up visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Leuprorelin Acetate Depot 3M 11.25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAE) | 27 Participants |
Secondary
Percentage of Participants With Decreased First Morning Voided (FMV) Urinary Gonadotropin (Gn) at Week 24
Time frame: Baseline and Week 24
Population: The enrolled population set included all the eligible participants enrolled in this study, i.e., all participants enrolled in this study who met the inclusion criteria and did not meet any of the exclusion criteria, regardless of whether they received the study drug. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Leuprorelin Acetate Depot 3M 11.25 mg | Percentage of Participants With Decreased First Morning Voided (FMV) Urinary Gonadotropin (Gn) at Week 24 | Decrease in FMV Gn Urinary LH Values | 62.03 percentage of participants |
| Leuprorelin Acetate Depot 3M 11.25 mg | Percentage of Participants With Decreased First Morning Voided (FMV) Urinary Gonadotropin (Gn) at Week 24 | Decrease in FMV Gn Urinary FSH Values | 63.29 percentage of participants |
Secondary
Percentage of Participants With Decreased Ratio of Bone Age Over Chronological Age at Week 24
Bone age was determined by Greulich and Pyle standards or Tanner-Whitehouse 3 (TW3) standards.
Time frame: Baseline and Week 24
Population: The enrolled population set included all the eligible participants enrolled in this study, i.e., all participants enrolled in this study who met the inclusion criteria and did not meet any of the exclusion criteria, regardless of whether they received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Leuprorelin Acetate Depot 3M 11.25 mg | Percentage of Participants With Decreased Ratio of Bone Age Over Chronological Age at Week 24 | 84.81 percentage of participants |
Secondary
Percentage of Participants With Tanner Stage Regression or No Progression at Week 24
Tanner Stage was used to measure pubertal development. Tanner Stage was based on progression through 5-stages. The progression was defined as either breast/genitals or pubic hair score had increased score compared with baseline score. Otherwise, the status was classified as regression or no progression. Baseline is defined as the assessment prior to the first dose of study drug.
Time frame: Baseline and Week 24
Population: The enrolled population set included all the eligible participants enrolled in this study, i.e., all participants enrolled in this study who met the inclusion criteria and did not meet any of the exclusion criteria, regardless of whether they received the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Leuprorelin Acetate Depot 3M 11.25 mg | Percentage of Participants With Tanner Stage Regression or No Progression at Week 24 | Tanner Stage Regression or No Progression | 97.47 percentage of participants |
| Leuprorelin Acetate Depot 3M 11.25 mg | Percentage of Participants With Tanner Stage Regression or No Progression at Week 24 | Tanner Stage Regression | 32.91 percentage of participants |
| Leuprorelin Acetate Depot 3M 11.25 mg | Percentage of Participants With Tanner Stage Regression or No Progression at Week 24 | No Tanner Stage Progression | 64.56 percentage of participants |