Brief Summary
The primary objective of this study is to evaluate the efficacy of Debio 4326 in suppressing serum luteinizing hormone (LH) to prepubertal levels 52 weeks after the first Debio 4326 injection in pediatric participants with central precocious puberty (CPP).
Brief Title
A Study to Assess the Efficacy, Safety, and Pharmacokinetics of Debio 4326 in Pediatric Participants With Central Precocious Puberty (LIBELULA™ Clinical Trial)
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
+41 21 321 01 11
Central Contact Email
clinicaltrials@debiopharm.com
Completion Date
Completion Date Type
Estimated
Conditions
Central Precocious Puberty
Eligibility Criteria
Inclusion Criteria:
1. Diagnosis of central precocious puberty.
2. Onset of development of sex characteristics (i.e., breast development in girls or testicular enlargement in boys according to the Tanner method) before the age of 8 years in girls and 9 years in boys.
3. Initially, only participants aged (a) 5 to 8 years inclusive (i.e., \<9 years) are eligible. The Sponsor will determine based on the recommendation of the DMC following the interim analysis whether participants aged (b) 2 to 4 years inclusive (i.e., \<5 years) and/or (c) 9 to 10 years inclusive (i.e., \<11 years) may be recruited.
4. Participant to receive at least 1 year of gonadotropin-releasing hormone agonist (GnRHa) therapy from study treatment start.
5. (a) Pre-treated participants: Start of initial GnRHa therapy no later than 18 months after onset of the first signs of CPP.
(b) Treatment-naive participants: Start of Debio 4326 treatment no later than 18 months after onset of the first signs of CPP.
6. (a) Pre-treated participants: Difference between bone age (Greulich and Pyle method) and chronological age of ≥1 year based on historical values at the initiation of the GnRHa therapy.
(b) Treatment-naive participants: Difference between bone age (Greulich and Pyle method) and chronological age of ≥1 year.
7. (a) Pre-treated participants: Pubertal-type LH response (LH ≥6 IU/L) following a GnRH/GnRHa stimulation test, or random non-stimulated serum LH \>0.5 IU/L (if considered local standard of care), based on historical values prior to the initiation of GnRHa therapy.
(b) Treatment-naive participants: Pubertal-type LH response (≥6 IU/L) 30 minutes following a GnRHa \[leuprolide acetate 20 micrograms per kilogram (μg/kg) subcutaneous injection (SC)\] stimulation test before treatment initiation.
8. (a) Pre-treated participants: Clinical evidence of puberty, defined as Tanner Staging ≥2 for breast development for girls and testicular volume ≥4 milliliter (mL) (cubic centimeter \[cc\]) for boys, prior to the initiation of GnRHa therapy.
(b) Treatment-naive participants: Clinical evidence of puberty, defined as Tanner Staging ≥2 for breast development for girls and testicular volume ≥4 mL (cc) for boys.
Exclusion Criteria:
1. Gonadotropin-independent (peripheral) precocious puberty: gonadotropin-independent gonadal or adrenal sex steroid secretion.
2. (a) Pre-treated participants: Non-progressing, isolated premature thelarche prior to the initial GnRHa therapy.
(b) Treatment-naive participants: Non-progressing, isolated premature thelarche.
3. Presence of an unstable intracranial tumor or an intracranial tumor potentially requiring neurosurgery or cerebral irradiation. Participants with hamartomas not requiring surgery are eligible.
4. Any other condition or chronic illness possibly interfering with growth (e.g., renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumor).
5. Other than GnRHa therapy in pre-treated participants, any ongoing treatment with a potential effect on serum levels of gonadotropins or sex steroids, or possibly interfering with growth, opioids, central nervous system \[CNS\] stimulants).
6. Prior or current therapy with medroxyprogesterone acetate, growth hormone, or Insulin-like growth factor-1 (IGF-1).
7. Diagnosis of short stature, i.e., more than 2.25 standard deviations (SD) below the mean height-for-age.
8. Known history of seizures, epilepsy, and/or central nervous system disorders that may have been associated with seizures or convulsions.
9. Prior (within 2 months of study treatment start) or current use of medications that have been associated with seizures or convulsions.
10. Use of anticoagulants (heparin or coumarin derivatives).
Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.
1. Diagnosis of central precocious puberty.
2. Onset of development of sex characteristics (i.e., breast development in girls or testicular enlargement in boys according to the Tanner method) before the age of 8 years in girls and 9 years in boys.
3. Initially, only participants aged (a) 5 to 8 years inclusive (i.e., \<9 years) are eligible. The Sponsor will determine based on the recommendation of the DMC following the interim analysis whether participants aged (b) 2 to 4 years inclusive (i.e., \<5 years) and/or (c) 9 to 10 years inclusive (i.e., \<11 years) may be recruited.
4. Participant to receive at least 1 year of gonadotropin-releasing hormone agonist (GnRHa) therapy from study treatment start.
5. (a) Pre-treated participants: Start of initial GnRHa therapy no later than 18 months after onset of the first signs of CPP.
(b) Treatment-naive participants: Start of Debio 4326 treatment no later than 18 months after onset of the first signs of CPP.
6. (a) Pre-treated participants: Difference between bone age (Greulich and Pyle method) and chronological age of ≥1 year based on historical values at the initiation of the GnRHa therapy.
(b) Treatment-naive participants: Difference between bone age (Greulich and Pyle method) and chronological age of ≥1 year.
7. (a) Pre-treated participants: Pubertal-type LH response (LH ≥6 IU/L) following a GnRH/GnRHa stimulation test, or random non-stimulated serum LH \>0.5 IU/L (if considered local standard of care), based on historical values prior to the initiation of GnRHa therapy.
(b) Treatment-naive participants: Pubertal-type LH response (≥6 IU/L) 30 minutes following a GnRHa \[leuprolide acetate 20 micrograms per kilogram (μg/kg) subcutaneous injection (SC)\] stimulation test before treatment initiation.
8. (a) Pre-treated participants: Clinical evidence of puberty, defined as Tanner Staging ≥2 for breast development for girls and testicular volume ≥4 milliliter (mL) (cubic centimeter \[cc\]) for boys, prior to the initiation of GnRHa therapy.
(b) Treatment-naive participants: Clinical evidence of puberty, defined as Tanner Staging ≥2 for breast development for girls and testicular volume ≥4 mL (cc) for boys.
Exclusion Criteria:
1. Gonadotropin-independent (peripheral) precocious puberty: gonadotropin-independent gonadal or adrenal sex steroid secretion.
2. (a) Pre-treated participants: Non-progressing, isolated premature thelarche prior to the initial GnRHa therapy.
(b) Treatment-naive participants: Non-progressing, isolated premature thelarche.
3. Presence of an unstable intracranial tumor or an intracranial tumor potentially requiring neurosurgery or cerebral irradiation. Participants with hamartomas not requiring surgery are eligible.
4. Any other condition or chronic illness possibly interfering with growth (e.g., renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumor).
5. Other than GnRHa therapy in pre-treated participants, any ongoing treatment with a potential effect on serum levels of gonadotropins or sex steroids, or possibly interfering with growth, opioids, central nervous system \[CNS\] stimulants).
6. Prior or current therapy with medroxyprogesterone acetate, growth hormone, or Insulin-like growth factor-1 (IGF-1).
7. Diagnosis of short stature, i.e., more than 2.25 standard deviations (SD) below the mean height-for-age.
8. Known history of seizures, epilepsy, and/or central nervous system disorders that may have been associated with seizures or convulsions.
9. Prior (within 2 months of study treatment start) or current use of medications that have been associated with seizures or convulsions.
10. Use of anticoagulants (heparin or coumarin derivatives).
Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.
Inclusion Criteria
Inclusion Criteria:
1. Diagnosis of central precocious puberty.
2. Onset of development of sex characteristics (i.e., breast development in girls or testicular enlargement in boys according to the Tanner method) before the age of 8 years in girls and 9 years in boys.
3. Initially, only participants aged (a) 5 to 8 years inclusive (i.e., \<9 years) are eligible. The Sponsor will determine based on the recommendation of the DMC following the interim analysis whether participants aged (b) 2 to 4 years inclusive (i.e., \<5 years) and/or (c) 9 to 10 years inclusive (i.e., \<11 years) may be recruited.
4. Participant to receive at least 1 year of gonadotropin-releasing hormone agonist (GnRHa) therapy from study treatment start.
5. (a) Pre-treated participants: Start of initial GnRHa therapy no later than 18 months after onset of the first signs of CPP.
(b) Treatment-naive participants: Start of Debio 4326 treatment no later than 18 months after onset of the first signs of CPP.
6. (a) Pre-treated participants: Difference between bone age (Greulich and Pyle method) and chronological age of ≥1 year based on historical values at the initiation of the GnRHa therapy.
(b) Treatment-naive participants: Difference between bone age (Greulich and Pyle method) and chronological age of ≥1 year.
7. (a) Pre-treated participants: Pubertal-type LH response (LH ≥6 IU/L) following a GnRH/GnRHa stimulation test, or random non-stimulated serum LH \>0.5 IU/L (if considered local standard of care), based on historical values prior to the initiation of GnRHa therapy.
(b) Treatment-naive participants: Pubertal-type LH response (≥6 IU/L) 30 minutes following a GnRHa \[leuprolide acetate 20 micrograms per kilogram (μg/kg) subcutaneous injection (SC)\] stimulation test before treatment initiation.
8. (a) Pre-treated participants: Clinical evidence of puberty, defined as Tanner Staging ≥2 for breast development for girls and testicular volume ≥4 milliliter (mL) (cubic centimeter \[cc\]) for boys, prior to the initiation of GnRHa therapy.
(b) Treatment-naive participants: Clinical evidence of puberty, defined as Tanner Staging ≥2 for breast development for girls and testicular volume ≥4 mL (cc) for boys.
inclusion/
1. Diagnosis of central precocious puberty.
2. Onset of development of sex characteristics (i.e., breast development in girls or testicular enlargement in boys according to the Tanner method) before the age of 8 years in girls and 9 years in boys.
3. Initially, only participants aged (a) 5 to 8 years inclusive (i.e., \<9 years) are eligible. The Sponsor will determine based on the recommendation of the DMC following the interim analysis whether participants aged (b) 2 to 4 years inclusive (i.e., \<5 years) and/or (c) 9 to 10 years inclusive (i.e., \<11 years) may be recruited.
4. Participant to receive at least 1 year of gonadotropin-releasing hormone agonist (GnRHa) therapy from study treatment start.
5. (a) Pre-treated participants: Start of initial GnRHa therapy no later than 18 months after onset of the first signs of CPP.
(b) Treatment-naive participants: Start of Debio 4326 treatment no later than 18 months after onset of the first signs of CPP.
6. (a) Pre-treated participants: Difference between bone age (Greulich and Pyle method) and chronological age of ≥1 year based on historical values at the initiation of the GnRHa therapy.
(b) Treatment-naive participants: Difference between bone age (Greulich and Pyle method) and chronological age of ≥1 year.
7. (a) Pre-treated participants: Pubertal-type LH response (LH ≥6 IU/L) following a GnRH/GnRHa stimulation test, or random non-stimulated serum LH \>0.5 IU/L (if considered local standard of care), based on historical values prior to the initiation of GnRHa therapy.
(b) Treatment-naive participants: Pubertal-type LH response (≥6 IU/L) 30 minutes following a GnRHa \[leuprolide acetate 20 micrograms per kilogram (μg/kg) subcutaneous injection (SC)\] stimulation test before treatment initiation.
8. (a) Pre-treated participants: Clinical evidence of puberty, defined as Tanner Staging ≥2 for breast development for girls and testicular volume ≥4 milliliter (mL) (cubic centimeter \[cc\]) for boys, prior to the initiation of GnRHa therapy.
(b) Treatment-naive participants: Clinical evidence of puberty, defined as Tanner Staging ≥2 for breast development for girls and testicular volume ≥4 mL (cc) for boys.
inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
8 Years
Minimum Age
5 Years
NCT Id
NCT06129539
Org Class
Industry
Org Full Name
Debiopharm International SA
Org Study Id
Debio 4326-301
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
LIBELULA™: An Open-label, Single-arm, Multi-center, Phase 3 Study on the Efficacy, Safety, and Pharmacokinetics of Debio 4326, a Triptorelin 12-month Formulation, in Pediatric Participants With Central Precocious Puberty
Primary Outcomes
Outcome Measure
Part A: Percentage of Participants With Suppression of Gonadotropin-Releasing Hormone Agonist Stimulated Serum Luteinizing Hormone (LH) to Less Than or Equal to (≤)5 International Units per Liter (IU/L)
Outcome Time Frame
Week 52 in Part A
Secondary Outcomes
Outcome Time Frame
Up to 104 weeks
Outcome Measure
Parts A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Serious TEAEs
Outcome Time Frame
Up to 104 weeks
Outcome Measure
Parts A and B: Number of Participants with Clinically Significant Abnormalities in Vital Signs
Outcome Time Frame
Up to 104 weeks
Outcome Measure
Parts A and B: Change From Baseline in Body Weight
Outcome Time Frame
Up to 104 weeks
Outcome Measure
Parts A and B: Change From Baseline in Body Mass Index
Outcome Time Frame
Up to 2 hours post-dose on Day 1 in both Parts A and B
Outcome Measure
Parts A and B: Number of Participants With Erythema, Swelling, and Induration at the Injection Site Immediately and 2 Hours After Each Debio 4326 Injection as per Investigator's Assessment
Outcome Time Frame
Up to 2 hours post-dose on Day 1 in both Parts A and B
Outcome Measure
Parts A and B: Number of Participants With Pain at the Injection Site Immediately and 2 Hours After Each Debio 4326 Injection as per Participant's Assessment Using the Wong-Baker FACES® Pain Rating Scale
Outcome Time Frame
Up to 48 hours post-dose on Day 3 in both Parts A and B
Outcome Measure
Parts A and B: Percentage of Participants Who do not Exhibit the Acute-on-Chronic (AOC) Phenomenon
Outcome Time Frame
Up to Week 52 in both Parts A and B
Outcome Measure
Parts A and B: Percentage of Participants With Stimulated Serum LH ≤5 IU/L
Outcome Time Frame
Up to Week 52 in both Parts A and B
Outcome Measure
Parts A and B: Percentage of Participants With Stimulated Serum LH ≤4 IU/L
Outcome Description
The following hormones will be assessed: basal LH, follicle-stimulating hormone (FSH), estradiol, testosterone, GnRHa-stimulated LH, and GnRHa-stimulated FSH.
Outcome Time Frame
Up to Week 52 in both Parts A and B
Outcome Measure
Parts A and B: Number of Participants With Change in Hormone Levels
Outcome Time Frame
Up to Week 52 in both Parts A and B
Outcome Measure
Parts A and B: Percentage of Girls With Prepubertal Serum Estradiol <20 pg/mL (<73 pmol/L)
Outcome Time Frame
Up to Week 52 in both Parts A and B
Outcome Measure
Parts A and B: Percentage of Boys With Testosterone <30 ng/dL (<1.0 nmol/L)
Outcome Time Frame
Baseline, up to Week 52 in both Parts A and B
Outcome Measure
Parts A and B: Change From Baseline in Height-for-Age Z Score
Outcome Time Frame
Up to Week 52 in both Parts A and B
Outcome Measure
Parts A and B: Number of Participants With Change From Baseline in Growth Velocity
Outcome Time Frame
Part A: Baseline, up to Week 52 in both Parts A and B
Outcome Measure
Percentage of Participants in Whom the Bone Age/Chronological Age Did Not Rise Relative to Baseline
Outcome Time Frame
Baseline, Weeks 26 and 52 in both Parts A and B
Outcome Measure
Parts A and B: Percentage of Participants Who Achieve Stabilization of Sexual Maturation (Regression or Stabilization Compared to Baseline by Tanner Staging)
Outcome Time Frame
Weeks 26 and 52 in both Parts A and B
Outcome Measure
Parts A and B: Percentage of Girls With Regression of Uterine Length (Using Transabdominal Ultrasound)
Outcome Time Frame
Weeks 26 and 52 in both Parts A and B
Outcome Measure
Parts A and B: Percentage of Boys With Absence of Progression of Testis Volumes (Clinical Assessment With Orchidometer)
Outcome Description
The pharmacokinetics (PK) of triptorelin will be evaluated in plasma.
Outcome Time Frame
Pre-dose and at multiple timepoints post-dose up to 52 weeks in Part A and 64 weeks in Part B
Outcome Measure
Parts A and B: Plasma Concentration of Triptorelin
Outcome Description
This outcome measure will be analyzed only in participants who stop all hormonal treatment with any GnRHa at end of treatment (EOT).
Outcome Time Frame
64 weeks after the last Debio 4326 injection in Part A or B
Outcome Measure
Percentage of Participants With Stimulated Serum LH Levels Greater Than (>)5 IU/L at Post Treatment Visit (PTV)
Outcome Time Frame
At multiple timepoints post-dose up to 48 hours (Day 2) in Part B
Outcome Measure
Part B: Accumulation Ratio on Maximum Serum Concentration (RacCmax)
Outcome Time Frame
At multiple timepoints post-dose up to 52 weeks in Part B
Outcome Measure
Part B: Accumulation Ratio on Serum Concentration at the End of the Dosing Interval (RacCtrough)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
8
Minimum Age Number (converted to Years and rounded down)
5
Investigators
Investigator Type
Principal Investigator
Investigator Name
Laurie Cohen
Investigator Email
lacohen@montefiore.org