Debio 4326 for Precocious Puberty

(LIBELULA Trial)

Recruiting at 50 trial locations

Overseen By Simona Ispas-Jouron

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Debiopharm International SA

Must be taking: GnRHa therapy

Must not be taking: Medroxyprogesterone, Growth hormone, IGF-1

Disqualifiers: Peripheral precocious puberty, Intracranial tumor, Diabetes, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

56 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing an injectable medication called Debio 4326. It is aimed at children who start puberty too early and are already receiving another treatment. The goal is to lower a hormone that triggers puberty, helping to delay its onset.

Will I have to stop taking my current medications?

The trial requires participants to be on GnRHa therapy, but you cannot be on other treatments that affect hormone levels or growth. If you're taking medications like medroxyprogesterone acetate, growth hormone, or IGF-1, you would need to stop those before joining the trial.

What data supports the effectiveness of the drug Debio 4326 for treating precocious puberty?

Research shows that triptorelin, a component of Debio 4326, is effective in treating central precocious puberty (CPP) by helping manage early puberty and improve final adult height. Studies have demonstrated its efficacy in various formulations, including 3-month and 6-month versions, for managing CPP. ^{1 2 3 4 5}

Is Debio 4326 (Triptorelin) safe for treating precocious puberty?

Research on Triptorelin, including various formulations, shows it is generally safe for treating central precocious puberty in children. Studies have reported effective suppression of puberty-related hormones with manageable side effects. ^{1 3 6 7 8}

How is the drug Debio 4326 different from other treatments for precocious puberty?

Debio 4326, a 12-month formulation of triptorelin, is unique because it reduces the frequency of injections needed for treating precocious puberty, offering greater convenience compared to the more common 1-, 3-, and 6-month formulations. ^{1 2 3 6 9}

Research Team

Study Director

Principal Investigator

Debiopharm International SA

Eligibility Criteria

This trial is for children diagnosed with central precocious puberty (CPP) who are already on hormone therapy. It's open to kids aged 5-8, and possibly older or younger after an interim review. They should have started puberty early—before age 8 in girls and 9 in boys—and begun treatment within 18 months of these first signs.

Inclusion Criteria

I developed early signs of puberty before age 8 (if girl) or 9 (if boy).

I am between 5 and 8 years old.

I will be on hormone therapy for at least 1 year starting now.

Exclusion Criteria

My early breast development has not worsened before starting hormone therapy.

I have a brain tumor that might need surgery or radiation.

I am currently on treatment that could affect my hormone levels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive the first injection of Debio 4326

52 weeks

Multiple visits for monitoring hormone levels and pharmacokinetics

Treatment Part B

Participants receive the second injection of Debio 4326

52 weeks

Multiple visits for monitoring hormone levels and pharmacokinetics

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Post Treatment Visit (PTV) for final assessments

Treatment Details

Interventions

• Debio 4326

Trial Overview The study tests Debio 4326's ability to maintain low levels of a puberty-related hormone over a year in kids treated for CPP. The goal is to see if this drug can effectively keep the signs of early puberty under control when used alongside standard hormone therapy.

Participant Groups

Group I: Debio 4326 Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Debiopharm International SA

Lead Sponsor

Trials

53

Recruited

7,300+

Findings from Research

Triptorelin 3.75 mg administered every 6 weeks effectively improved final adult height in girls with idiopathic central precocious puberty, with final heights exceeding target heights by an average of 1.51 cm for those treated with triptorelin alone and 4.86 cm for those receiving triptorelin with growth hormone.

The combination of triptorelin and recombinant human growth hormone resulted in greater height gains, while maintaining a stable body mass index and restoring ovarian function post-treatment, with no significant side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty. Liang, Y., Wei, H., Li, J., et al.[2022]

In a meta-analysis of 153 children with central precocious puberty, triptorelin 11.25 mg effectively suppressed luteinising hormone (LH) levels in 87.6% of participants at 3 months and 92.8% at 6 months, indicating strong efficacy in hormone regulation.

The treatment also successfully suppressed other hormones, with 86.7% of children showing reduced follicle-stimulating hormone (FSH), 97.1% showing reduced oestradiol in girls, and 72.7% showing reduced testosterone in boys at the 3-month mark, demonstrating its effectiveness in managing CPP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-Analysis of Paediatric Patients with Central Precocious Puberty Treated with Intramuscular Triptorelin 11.25 mg 3-Month Prolonged-Release Formulation . Durand, A., Tauber, M., Patel, B., et al.[2019]

Triptorelin pamoate 11.25 mg, given every 3 months, effectively suppresses luteinising hormone (LH) levels in 83.8% of patients with central precocious puberty (CPP) after 3 months, indicating its efficacy in managing this condition.

The treatment is well-tolerated, with mild to moderate adverse events that resolved without lasting effects, showing a safety profile comparable to triptorelin acetate, based on a study involving 37 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 6-Month Trial of the Efficacy and Safety of Triptorelin Pamoate (11.25 mg) Every 3 Months in Children with Precocious Puberty: A Retrospective Comparison with Triptorelin Acetate. Zenaty, D., Blumberg, J., Liyanage, N., et al.[2018]

Treatment with the GnRH agonist triptorelin in children with central precocious puberty (CPP) significantly increased final height, with an average increase from a predicted height of 158.2 cm to a final height of 161.6 cm after treatment.

The study involved 36 children (31 girls and 5 boys) treated for an average of 3.4 years, and it was found that starting height was the most important factor influencing final height, while bone age at treatment cessation negatively affected growth outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final height in central precocious puberty after long term treatment with a slow release GnRH agonist. Oostdijk, W., Rikken, B., Schreuder, S., et al.[2022]

In a phase III study involving 44 treatment-naïve children with central precocious puberty (CPP), the 6-month formulation of triptorelin effectively suppressed luteinizing hormone (LH) levels to pre-pubertal levels in 93.2% of patients by month 6, with sustained suppression through month 12.

The study reported no unexpected drug-related adverse events, indicating that the triptorelin 6-month formulation is both safe and well-tolerated, potentially improving treatment compliance due to its extended injection interval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty. Klein, K., Yang, J., Aisenberg, J., et al.[2019]

The 6-month formulation of triptorelin effectively suppressed hormone levels in children with central precocious puberty (CPP), stabilizing the pituitary-gonadal axis without any observed adverse effects during the treatment period.

Treatment with the 6-month triptorelin formulation led to an increase in predicted adult height (PAH), indicating its efficacy in managing CPP and suggesting a potential shift towards long-acting treatments for greater convenience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of 6-month triptorelin formulation on predicted adult height and basal gonadotropin levels in patients with central precocious puberty. Yoo, E., Kim, S., Jung, HL., et al.[2023]

In a study of seven children with central precocious puberty, both subcutaneous (DDsc) and intramuscular (DDim) formulations of triptorelin effectively suppressed hormone levels and slowed bone maturation over a 6-month period, demonstrating their efficacy in treating CPP.

The subcutaneous formulation (DDsc) was found to be more acceptable to patients, with five out of seven children preferring it due to less fear of injections, while parents rated it equal or better than the intramuscular version in terms of treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the subcutaneous reformulated triptorelin depot in children with central precocious puberty. Partsch, CJ., von Büren, E., Brand, M., et al.[2019]

In a 12-month study involving 32 Chinese children with central precocious puberty (CPP), the 3-month formulation of triptorelin effectively suppressed luteinizing hormone (LH) levels to prepubertal levels in nearly all participants (100% at month 3, 93.5% at months 6 and 12).

The triptorelin treatment was well tolerated, showing a similar efficacy and safety profile to previous studies in non-Chinese populations, making it a viable treatment option for CPP in Chinese children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Triptorelin 3-Month Formulation in Chinese Children with Central Precocious Puberty: A Phase 3, Open-Label, Single-Arm Study. Luo, X., Zhang, C., Yang, Y., et al.[2023]

In a study of 106 girls with central precocious puberty (CPP), the 3-month triptorelin depot was found to be as effective as the 1-month depot in suppressing hormone levels and inhibiting bone maturation.

Both the 3-month and 1-month triptorelin treatments resulted in similar rates of suppressed luteinizing hormone (LH) levels after 6 months and 1 year, indicating that the longer-acting formulation is a viable option for managing CPP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Triptorelin 3-Month Depot Compared to 1-Month Depot for the Treatment of Korean Girls with Central Precocious Puberty in Single Tertiary Center. Chung, LY., Kang, E., Nam, HK., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Meta-Analysis of Paediatric Patients with Central Precocious Puberty Treated with Intramuscular Triptorelin 11.25 mg 3-Month Prolonged-Release Formulation . [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A 6-Month Trial of the Efficacy and Safety of Triptorelin Pamoate (11.25 mg) Every 3 Months in Children with Precocious Puberty: A Retrospective Comparison with Triptorelin Acetate. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Final height in central precocious puberty after long term treatment with a slow release GnRH agonist. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of 6-month triptorelin formulation on predicted adult height and basal gonadotropin levels in patients with central precocious puberty. [2023]

7. Norway pubmed.ncbi.nlm.nih.gov

Efficacy of the subcutaneous reformulated triptorelin depot in children with central precocious puberty. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Triptorelin 3-Month Formulation in Chinese Children with Central Precocious Puberty: A Phase 3, Open-Label, Single-Arm Study. [2023]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy of Triptorelin 3-Month Depot Compared to 1-Month Depot for the Treatment of Korean Girls with Central Precocious Puberty in Single Tertiary Center. [2021]