Debio 4326 for Precocious Puberty

(LIBELULA Trial)

Not currently recruiting at 54 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Debio 4326 (also known as Triptorelin 12-month formulation) to determine its effectiveness in managing central precocious puberty (CPP), a condition where puberty begins too early in children. The goal is to assess whether Debio 4326 can lower certain hormone levels to prepubertal levels over a year. Children who have shown early signs of puberty, such as breast development in girls or testicular enlargement in boys, may qualify if they have not received treatment for more than a year. As a Phase 3 trial, this study represents the final step before FDA approval, providing an opportunity to access a potentially effective treatment early.

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.

Is there any evidence suggesting that Debio 4326 is likely to be safe for humans?

Research shows that Debio 4326, a once-a-year injection, treats early puberty in children. It is a long-lasting version of the drug triptorelin.

Studies have found that this treatment is generally well-tolerated, with most children not experiencing serious side effects. Researchers have assessed both the drug's effectiveness and safety, monitoring participants for a year after their first injection.

Triptorelin, the main ingredient, is already used in other treatments, providing extensive safety data. Similar studies have shown the drug to be safe, with manageable side effects. Common side effects include redness or swelling at the injection site.

The current trial is in a later stage, indicating more evidence about the treatment's safety. Overall, Debio 4326 appears to be a promising option for children with early puberty. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for precocious puberty?

Debio 4326 is unique because it offers a novel approach to treating precocious puberty with a streamlined treatment schedule. Unlike standard treatments that typically require monthly or quarterly injections, Debio 4326 is administered in just two doses over a year. This extended dosing schedule could improve patient compliance and convenience. Researchers are excited about this treatment as it could simplify the management of precocious puberty, potentially making life easier for both patients and their families.

What evidence suggests that Debio 4326 might be an effective treatment for precocious puberty?

Research shows that Debio 4326, a special version of the drug triptorelin, helps manage central precocious puberty (CPP) by lowering luteinizing hormone (LH) to pre-puberty levels. This hormone plays a key role in triggering early puberty. Previous studies with a similar triptorelin version, administered every three months, successfully lowered LH levels in about 83.8% of children with CPP. In this trial, participants will receive Debio 4326, which aims to achieve the same results with fewer injections, as it lasts for 12 months. This suggests it could effectively and conveniently control early puberty in children. ^{1 2 3 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

Debiopharm International SA

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

Citations

1. childrens.com childrens.com/research-innovation/clinical-trials/stu-2023-1195

Debio 4326-301: An open-label, single-arm, multi-center ... This is an open-label, single-arm, multi-center, Phase 3 study of Debio 4326, a triptorelin acetate 70 mg, 12-month extended-release formulation

2. withpower.com withpower.com/trial/phase-3-puberty-precocious-11-2023-7bd35

Debio 4326 for Precocious Puberty (LIBELULA Trial) Triptorelin pamoate 11.25 mg, given every 3 months, effectively suppresses luteinising hormone (LH) levels in 83.8% of patients with central precocious puberty ...

3. debiopharm.com debiopharm.com/drug-development/press-releases/first-patients-dosed-in-debiopharms-phase-iii-trial-libelula-investigating-debio-4326-a-12-month-triptorelin-formulation-for-children-with-central-precocious-puberty

First Patients Dosed in Debiopharm's Phase III Trial ... Debio 4326 is a unique injectable, biodegradable 12-month extended-release formulation of triptorelin designed to further reduce the frequency of injections ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06129539?term=debio&rank=7

NCT06129539 | A Study to Assess the Efficacy, Safety, and ... 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 ...

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06129539

Debio 4326 in Pediatric Participants With Central ... 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11550251/

A Phase 3, Open-Label, Single-Arm Trial of the Efficacy and ... This phase 3 study assessed the efficacy, safety, and pharmacokinetics of the 6-month prolonged release (PR) formulation in Chinese children ...