A Study to Assess the Efficacy, Safety, and Pharmacokinetics of Debio 4326 in Pediatric Participants With Central Precocious Puberty (LIBELULA™ Clinical Trial) (LIBELULA)

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Central Precocious Puberty
• Intervention / Treatment: Drug: Debio 4326

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1012AAR
    • Instituto de Investigaciones Metabolicas (IDIM)
  • Buenos Aires, Argentina, C1425AGC
    • Centro Medico Dra Laura Maffei Investigacion Clinica Aplicada
  • Mar del Plata, Argentina, B7600FYK
    • Centro de Investigaciones Medicas Mar Del Plata
  • San Miguel de Tucumán, Argentina, T4000
    • Clínica Mayo de Urgencias Médicas Cruz Blanca S.R.L
• Brazil
  • Brasília, Brazil, 70684-831
    • Hospital Da Criança de Brasília Jose Alencar
  • Fortaleza, Brazil, 60430-270
    • Hospital Universitario Walter Cantidio
  • Lago Sul, Brazil, 71625175
    • Clínica de Endocrinologia e Metabologia Ltda
  • Porto Alegre, Brazil, 90430-001
    • Nucleo de Pesquisa Clínica do Rio Grande do Sul-NPCRS
  • São Paulo, Brazil, 01228000
    • CPQuali Pesquisa Clínica
  • São Paulo, Brazil, REG1 01222-020
    • Irmandade Santa Casa de São Paulo
  • Votuporanga, Brazil, 15501-405
    • INTEGRAL Pesquisa e Ensino
• Chile
  • Antofagasta, Chile, 1271987
    • ENDOMET
  • Santiago, Chile, 8360160
    • Hospital Clinico San Borja Arriaran (HCSBA)
• Mexico
  • Monterrey, Mexico, 64060
    • Christus Latam Hub Center of Excellence and Innovation S C
• United States
  • California
    • San Diego, California, United States, 92123
      • Rady Children's Hospital - San Diego
    • San Francisco, California, United States, 94143
      • University of California San Francisco-Benioff Children's Hospital
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Prisma Health Pediatric Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Debio 4326; Participants will receive the first injection of Debio 4326, on Day 1 in Part A followed by a second injection 52 weeks later in Part B of the study.	Drug: Debio 4326; Administered as an intramuscular (IM) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)	Week 52 in Part A

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Serious TEAEs		Up to 104 weeks
Parts A and B: Number of Participants with Clinically Significant Abnormalities in Vital Signs		Up to 104 weeks
Parts A and B: Change From Baseline in Body Weight		Up to 104 weeks
Parts A and B: Change From Baseline in Body Mass Index		Up to 104 weeks
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		Up to 2 hours post-dose on Day 1 in both Parts A and B
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		Up to 2 hours post-dose on Day 1 in both Parts A and B
Parts A and B: Percentage of Participants Who do not Exhibit the Acute-on-Chronic (AOC) Phenomenon		Up to 48 hours post-dose on Day 3 in both Parts A and B
Parts A and B: Percentage of Participants With Stimulated Serum LH ≤5 IU/L		Up to Week 52 in both Parts A and B
Parts A and B: Percentage of Participants With Stimulated Serum LH ≤4 IU/L		Up to Week 52 in both Parts A and B
Parts A and B: Number of Participants With Change in Hormone Levels	The following hormones will be assessed: basal LH, follicle-stimulating hormone (FSH), estradiol, testosterone, GnRHa-stimulated LH, and GnRHa-stimulated FSH.	Up to Week 52 in both Parts A and B
Parts A and B: Percentage of Girls With Prepubertal Serum Estradiol <20 pg/mL (<73 pmol/L)		Up to Week 52 in both Parts A and B
Parts A and B: Percentage of Boys With Testosterone <30 ng/dL (<1.0 nmol/L)		Up to Week 52 in both Parts A and B
Parts A and B: Change From Baseline in Height-for-Age Z Score		Baseline, up to Week 52 in both Parts A and B
Parts A and B: Number of Participants With Change From Baseline in Growth Velocity		Up to Week 52 in both Parts A and B
Percentage of Participants in Whom the Bone Age/Chronological Age Did Not Rise Relative to Baseline		Part A: Baseline, up to Week 52 in both Parts A and B
Parts A and B: Percentage of Participants Who Achieve Stabilization of Sexual Maturation (Regression or Stabilization Compared to Baseline by Tanner Staging)		Baseline, Weeks 26 and 52 in both Parts A and B
Parts A and B: Percentage of Girls With Regression of Uterine Length (Using Transabdominal Ultrasound)		Weeks 26 and 52 in both Parts A and B
Parts A and B: Percentage of Boys With Absence of Progression of Testis Volumes (Clinical Assessment With Orchidometer)		Weeks 26 and 52 in both Parts A and B
Parts A and B: Plasma Concentration of Triptorelin	The pharmacokinetics (PK) of triptorelin will be evaluated in plasma.	Pre-dose and at multiple timepoints post-dose up to 52 weeks in Part A and 64 weeks in Part B
Percentage of Participants With Stimulated Serum LH Levels Greater Than (>)5 IU/L at Post Treatment Visit (PTV)	This outcome measure will be analyzed only in participants who stop all hormonal treatment with any GnRHa at end of treatment (EOT).	64 weeks after the last Debio 4326 injection in Part A or B
Part B: Accumulation Ratio on Maximum Serum Concentration (RacCmax)		At multiple timepoints post-dose up to 48 hours (Day 2) in Part B
Part B: Accumulation Ratio on Serum Concentration at the End of the Dosing Interval (RacCtrough)		At multiple timepoints post-dose up to 52 weeks in Part B

Collaborators and Investigators

• Sponsor: Debiopharm International SA
• Investigators: Study Director: Study Director, Debiopharm International SA

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: November 8, 2023
• First Submitted That Met QC Criteria: November 8, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious
• Other Study ID Numbers: Debio 4326-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No