Clinical trial NCT06129539: A Study to Assess the Efficacy, Safety, and Pharmacokinetics of Debio 4326 in Pediatric Participants With Central Precocious Puberty (LIBELULA™ Clinical Trial)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Central Precocious Puberty
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2023-11-13
Enrollment: 56
Sex: ALL
Minimum age (years): 5
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
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)
timeFrame: Week 52 in Part A
Secondary outcomes:
measure: Parts A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Serious TEAEs
timeFrame: Up to 104 weeks
measure: Parts A and B: Number of Participants with Clinically Significant Abnormalities in Vital Signs
timeFrame: Up to 104 weeks
measure: Parts A and B: Change From Baseline in Body Weight
timeFrame: Up to 104 weeks
measure: Parts A and B: Change From Baseline in Body Mass Index
timeFrame: Up to 104 weeks
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
timeFrame: Up to 2 hours post-dose on Day 1 in both Parts A and B
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
timeFrame: Up to 2 hours post-dose on Day 1 in both Parts A and B
measure: Parts A and B: Percentage of Participants Who do not Exhibit the Acute-on-Chronic (AOC) Phenomenon
timeFrame: Up to 48 hours post-dose on Day 3 in both Parts A and B
measure: Parts A and B: Percentage of Participants With Stimulated Serum LH ≤5 IU/L
timeFrame: Up to Week 52 in both Parts A and B
measure: Parts A and B: Percentage of Participants With Stimulated Serum LH ≤4 IU/L
timeFrame: Up to Week 52 in both Parts A and B
measure: Parts A and B: Number of Participants With Change in Hormone Levels
timeFrame: Up to Week 52 in both Parts A and B
measure: Parts A and B: Percentage of Girls With Prepubertal Serum Estradiol <20 pg/mL (<73 pmol/L)
timeFrame: Up to Week 52 in both Parts A and B
measure: Parts A and B: Percentage of Boys With Testosterone <30 ng/dL (<1.0 nmol/L)
timeFrame: Up to Week 52 in both Parts A and B
measure: Parts A and B: Change From Baseline in Height-for-Age Z Score
timeFrame: Baseline, up to Week 52 in both Parts A and B
measure: Parts A and B: Number of Participants With Change From Baseline in Growth Velocity
timeFrame: Up to Week 52 in both Parts A and B
measure: Percentage of Participants in Whom the Bone Age/Chronological Age Did Not Rise Relative to Baseline
timeFrame: Part A: Baseline, up to Week 52 in both Parts A and B
measure: Parts A and B: Percentage of Participants Who Achieve Stabilization of Sexual Maturation (Regression or Stabilization Compared to Baseline by Tanner Staging)
timeFrame: Baseline, Weeks 26 and 52 in both Parts A and B
measure: Parts A and B: Percentage of Girls With Regression of Uterine Length (Using Transabdominal Ultrasound)
timeFrame: Weeks 26 and 52 in both Parts A and B
measure: Parts A and B: Percentage of Boys With Absence of Progression of Testis Volumes (Clinical Assessment With Orchidometer)
timeFrame: Weeks 26 and 52 in both Parts A and B
measure: Parts A and B: Plasma Concentration of Triptorelin
timeFrame: Pre-dose and at multiple timepoints post-dose up to 52 weeks in Part A and 64 weeks in Part B
measure: Percentage of Participants With Stimulated Serum LH Levels Greater Than (>)5 IU/L at Post Treatment Visit (PTV)
timeFrame: 64 weeks after the last Debio 4326 injection in Part A or B
measure: Part B: Accumulation Ratio on Maximum Serum Concentration (RacCmax)
timeFrame: At multiple timepoints post-dose up to 48 hours (Day 2) in Part B
measure: Part B: Accumulation Ratio on Serum Concentration at the End of the Dosing Interval (RacCtrough)
timeFrame: At multiple timepoints post-dose up to 52 weeks in Part B
Other outcomes:
Locations:
city: Tucson
country: United States
facility: TMC HealthCare
state: Arizona
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco-Benioff Children's Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado/Children's Hospital Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Wolfson's Children's Hospital
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Health
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H.Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University/Riley Hospital for Children
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Investigational Drug Service, The Children's Hospital of Philadelphia
state: Pennsylvania
city: Columbia
country: United States
facility: Prisma Health Pediatric Endocrinology
state: South Carolina
city: Dallas
country: United States
facility: Research Institute of Dallas
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System
state: Virginia
city: Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Metabolicas (IDIM)
city: Buenos Aires
country: Argentina
facility: Centro Medico Dra Laura Maffei Investigacion Clinica Aplicada
city: Buenos Aires
country: Argentina
facility: Hospital de Niños Dr. Ricardo Gutierrez
city: Córdoba
country: Argentina
facility: Centro Privado de Endocrinología
city: Mar del Plata
country: Argentina
facility: Centro de Investigaciones Medicas Mar del Plata
city: Tucuman
country: Argentina
facility: Clinica Mayo de Urgencias Medicas Cruz Blanca S.R.L
city: Belém
country: Brazil
facility: Hospital Universitário João de Barros Barreto
city: Brasília
country: Brazil
facility: Hospital Da Criança de Brasília Jose Alencar
city: Curitiba
country: Brazil
facility: CETI - Centro de Estudos em Terapias Inovadoras Ltda
city: Fortaleza
country: Brazil
facility: Hospital Universitario Walter Cantidio
city: Lago Sul
country: Brazil
facility: Clínica de Endocrinologia e Metabologia Ltda
city: Porto Alegre
country: Brazil
facility: Nucleo de Pesquisa Clínica do Rio Grande do Sul-NPCRS
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
city: São Paulo
country: Brazil
facility: CPCLIN - Centro de Pesquisas Clínicas Ltda.
city: São Paulo
country: Brazil
facility: Instituto PENSI - Pesquisa e Ensino em Saúde Infantil
city: São Paulo
country: Brazil
facility: CPQuali Pesquisa Clinica
city: São Paulo
country: Brazil
facility: Irmandade Santa Casa de São Paulo
city: Votuporanga
country: Brazil
facility: Integral Pesquisa e Ensino
city: Antofagasta
country: Chile
facility: ENDOMET
city: Santiago
country: Chile
facility: Hospital Clinico San Borja Arriaran (HCSBA)
city: Monterrey
country: Mexico
facility: Christus Latam Hub Center of Excellence and Innovation S C
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization S.C.
city: Puebla
country: Mexico
facility: Hospital Angeles Puebla
Study officials:
affiliation: Debiopharm International SA
name: Study Director
role: STUDY_DIRECTOR
References: