A Study to Assess the Efficacy, Safety, and Pharmacokinetics of Debio 4326 in Pediatric Participants With Central Precocious Puberty (LIBELULA™ Clinical Trial)
- Registration Number
- NCT06129539
- Lead Sponsor
- Debiopharm International SA
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 56
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Diagnosis of central precocious puberty.
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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.
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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.
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Participant to receive at least 1 year of gonadotropin-releasing hormone agonist (GnRHa) therapy from study treatment start.
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(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.
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(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.
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(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.
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(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.
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Gonadotropin-independent (peripheral) precocious puberty: gonadotropin-independent gonadal or adrenal sex steroid secretion.
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(a) Pre-treated participants: Non-progressing, isolated premature thelarche prior to the initial GnRHa therapy.
(b) Treatment-naive participants: Non-progressing, isolated premature thelarche.
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Presence of an unstable intracranial tumor or an intracranial tumor potentially requiring neurosurgery or cerebral irradiation. Participants with hamartomas not requiring surgery are eligible.
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Any other condition or chronic illness possibly interfering with growth (e.g., renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumor).
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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).
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Prior or current therapy with medroxyprogesterone acetate, growth hormone, or Insulin-like growth factor-1 (IGF-1).
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Diagnosis of short stature, i.e., more than 2.25 standard deviations (SD) below the mean height-for-age.
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Known history of seizures, epilepsy, and/or central nervous system disorders that may have been associated with seizures or convulsions.
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Prior (within 2 months of study treatment start) or current use of medications that have been associated with seizures or convulsions.
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Use of anticoagulants (heparin or coumarin derivatives).
Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Debio 4326 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 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 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: Change From Baseline in Body Mass Index Up to 104 weeks 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: Plasma Concentration of Triptorelin Pre-dose and at multiple timepoints post-dose up to 52 weeks in Part A and 64 weeks in Part B The pharmacokinetics (PK) of triptorelin will be evaluated in plasma.
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 Absence of Progression of Testis Volumes (Clinical Assessment With Orchidometer) Weeks 26 and 52 in both Parts A and B Percentage of Participants With Stimulated Serum LH Levels Greater Than (>)5 IU/L at Post Treatment Visit (PTV) 64 weeks after the last Debio 4326 injection in Part A or B This outcome measure will be analyzed only in participants who stop all hormonal treatment with any GnRHa at end of treatment (EOT).
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: 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: 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: 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: 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: 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 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 ≤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 Up to Week 52 in both Parts A and B The following hormones will be assessed: basal LH, follicle-stimulating hormone (FSH), estradiol, testosterone, GnRHa-stimulated LH, and GnRHa-stimulated FSH.
Related Research Topics
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Trial Locations
- Locations (44)
Hospital Universitario Walter Cantidio
🇧🇷Fortaleza, Brazil
Clínica de Endocrinologia e Metabologia Ltda
🇧🇷Lago Sul, Brazil
ENDOMET
🇨🇱Antofagasta, Chile
TMC HealthCare
🇺🇸Tucson, Arizona, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
University of California San Francisco-Benioff Children's Hospital
🇺🇸San Francisco, California, United States
University of Colorado/Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Wolfson's Children's Hospital
🇺🇸Jacksonville, Florida, United States
Nemours Children's Health
🇺🇸Pensacola, Florida, United States
Atlanta Diabetes Associates
🇺🇸Atlanta, Georgia, United States
Ann and Robert H.Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Indiana University/Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Children's Hospital at Montefiore
🇺🇸New York, New York, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Investigational Drug Service, The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Prisma Health Pediatric Endocrinology
🇺🇸Columbia, South Carolina, United States
Research Institute of Dallas
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Virginia Commonwealth University Health System
🇺🇸Richmond, Virginia, United States
Instituto de Investigaciones Metabolicas (IDIM)
🇦🇷Buenos Aires, Argentina
Centro Medico Dra Laura Maffei Investigacion Clinica Aplicada
🇦🇷Buenos Aires, Argentina
Hospital de Niños Dr. Ricardo Gutierrez
🇦🇷Buenos Aires, Argentina
Centro Privado de Endocrinología
🇦🇷Córdoba, Argentina
Centro de Investigaciones Medicas Mar del Plata
🇦🇷Mar del Plata, Argentina
Clinica Mayo de Urgencias Medicas Cruz Blanca S.R.L
🇦🇷Tucuman, Argentina
Hospital Universitário João de Barros Barreto
🇧🇷Belém, Brazil
Hospital Da Criança de Brasília Jose Alencar
🇧🇷Brasília, Brazil
CETI - Centro de Estudos em Terapias Inovadoras Ltda
🇧🇷Curitiba, Brazil
Nucleo de Pesquisa Clínica do Rio Grande do Sul-NPCRS
🇧🇷Porto Alegre, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto
🇧🇷São José do Rio Preto, Brazil
CPCLIN - Centro de Pesquisas Clínicas Ltda.
🇧🇷São Paulo, Brazil
Instituto PENSI - Pesquisa e Ensino em Saúde Infantil
🇧🇷São Paulo, Brazil
CPQuali Pesquisa Clinica
🇧🇷São Paulo, Brazil
Irmandade Santa Casa de São Paulo
🇧🇷São Paulo, Brazil
Integral Pesquisa e Ensino
🇧🇷Votuporanga, Brazil
Hospital Clinico San Borja Arriaran (HCSBA)
🇨🇱Santiago, Chile
Christus Latam Hub Center of Excellence and Innovation S C
🇲🇽Monterrey, Mexico
Oaxaca Site Management Organization S.C.
🇲🇽Oaxaca, Mexico
Hospital Angeles Puebla
🇲🇽Puebla, Mexico