Leuprolide for Precocious Puberty

Not currently recruiting at 51 trial locations

Overseen By Yisheng Lee, MD, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Foresee Pharmaceuticals Co., Ltd.

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

Disqualifiers: Peripheral precocious puberty, Intracranial tumor, Diabetes, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug Leuprolide Mesylate, a hormone therapy, is safe and effective for children with central precocious puberty (early puberty due to hormone issues). Participants will receive two injections of the drug, six months apart, to determine its effectiveness in managing their condition. Suitable candidates are children aged 2 to 8 for girls and 2 to 9 for boys, who show early signs of puberty, such as breast development or increased testicle size, and have not started other treatments for this condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are currently using medications associated with seizures or convulsions, you may need to stop them as they are excluded from the trial.

Is there any evidence suggesting that Leuprolide Mesylate is likely to be safe for humans?

Research has shown that Leuprolide Mesylate, a treatment for early puberty, is generally safe. Studies have found that its six-month injection has a safety record similar to other treatments, with manageable and expected side effects. For instance, a long-term study found that Leuprolide Mesylate does not affect body weight or cause early puberty to return later. It can also help children grow taller as adults. Overall, children with early puberty tolerate Leuprolide Mesylate well. ^{1 2 3 4 5}

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

Leuprolide Mesylate is unique because it offers a potentially more convenient dosing schedule for managing central precocious puberty. Unlike standard treatments that often require monthly injections, this new formulation only needs to be administered twice in a year, with doses given six months apart. This can significantly reduce the treatment burden for young patients and their families, making it an exciting advancement in treatment options. Researchers are optimistic that this less frequent dosing will maintain effectiveness while improving patient compliance and quality of life.

What evidence suggests that Leuprolide Mesylate might be an effective treatment for precocious puberty?

Research shows that Leuprolide Mesylate effectively treats early puberty, known as central precocious puberty (CPP). Studies on similar versions, such as the 1-month depot, have demonstrated positive effects on growth and help maintain normal adult height. After treatment, patients typically return to a normal puberty process, and girls often have regular periods by age 12. In this trial, participants will receive a 6-month depot version of Leuprolide, which other studies have found to effectively control hormone levels and growth in children with CPP. Overall, leuprolide treatments have safely managed early puberty symptoms, supporting their use for this condition. ^{3 4 6 7 8}

Who Is on the Research Team?

Bassem Elmankabadi

Principal Investigator

Foresee Pharma

Are You a Good Fit for This Trial?

This trial is for young children with early onset puberty: girls aged 2-8 and boys aged 2-9 who have been diagnosed with central precocious puberty (CPP) within the last year. They should not have had previous treatment for CPP, be able to participate in the study, and have parental consent.

Inclusion Criteria

Signed Institutional Review Board/Independent Ethics Committee (IRB/IEC)-approved informed consent form (ICF) by one or both parents (per IRB/IEC requirements), by the custodial parent(s) or by the legal guardian(s) (if required)

I am willing and able to participate in the study.

I was diagnosed with central precocious puberty less than a year ago and haven't received GnRHa treatment for it.

Exclusion Criteria

I have been treated with medroxyprogesterone, growth hormone, or IGF-1.

You are pregnant, as confirmed by a urine test.

My breast development started early but hasn't progressed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two injections of FP-001 42 mg, six months apart

48 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Leuprolide Mesylate

Trial Overview

The trial tests Leuprolide Mesylate's safety and effectiveness in treating CPP. It involves two subcutaneous injections of the drug given six months apart to see if it can safely delay early puberty symptoms.

How Is the Trial Designed?

Group I: FP-001 42 mg Experimental Treatment 1 Intervention

All subjects will be pediatric patients with central precocious puberty. They will be injected twice with a depot formulation containing 42 mg of Leuprolide. The first dose on day 0 the second dose on week 24 (six months apart).

Leuprolide Mesylate is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Leuprolide Mesylate for:

• Prostate cancer
• Breast cancer
• Endometriosis
• Uterine fibroids
• Central precocious puberty

Approved in European Union as Leuprorelin for:

• Prostate cancer
• Breast cancer
• Endometriosis
• Uterine fibroids
• Central precocious puberty

Approved in Canada as Leuprolide Mesylate for:

• Prostate cancer
• Breast cancer
• Endometriosis
• Uterine fibroids
• Central precocious puberty

Approved in Japan as Leuprorelin for:

• Prostate cancer
• Breast cancer
• Endometriosis
• Uterine fibroids
• Central precocious puberty

Who Is Running the Clinical Trial?

Foresee Pharmaceuticals Co., Ltd.

Lead Sponsor

Trials

15

Recruited

1,200+

Changchun GeneScience Pharmaceuticals Co., Ltd.

Industry Sponsor

Trials

47

Recruited

15,400+

QPS

Collaborator

Trials

4

Recruited

250+

QPS Holdings LLC

Industry Sponsor

Trials

10

Recruited

750+

Changchun GeneScience Pharmaceutical Co., Ltd.

Industry Sponsor

Trials

72

Recruited

18,700+

Dr. Lei Jin

Changchun GeneScience Pharmaceutical Co., Ltd.

Chief Executive Officer

PhD

Dr. Yuanfeng Xia

Changchun GeneScience Pharmaceutical Co., Ltd.

Chief Medical Officer

MD

GeneScience Pharmaceuticals Co., Ltd.

Industry Sponsor

Trials

47

Recruited

15,400+

Published Research Related to This Trial

The new 0.5% loteprednol etabonate (LE) gel formulation demonstrated prolonged retention on the ocular surface, with detectable LE levels in human tear fluid for up to 24 hours after a single dose.

In rabbits, LE reached maximum concentrations quickly in ocular tissues, indicating effective delivery to the eye, while systemic absorption was minimal, showing low plasma levels and no detectable LE after 4 hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged exposure to loteprednol etabonate in human tear fluid and rabbit ocular tissues following topical ocular administration of Lotemax gel, 0.5%. Glogowski, S., Lowe, E., Siou-Mermet, R., et al.[2015]

The new 3-month depot formulation of leuprolide acetate (Luphere 3M Depot) demonstrated a high encapsulation efficiency of 94.7% and a delayed release profile similar to the existing Lucrin Depot, indicating effective drug delivery.

In a study involving 20 prostate cancer patients, both Luphere 3M and Lucrin Depot were well tolerated with no serious adverse effects, showing comparable safety and pharmacokinetics between the two formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative in vitro release and clinical pharmacokinetics of leuprolide from Luphere 3M Depot, a 3-month release formulation of leuprolide acetate. Park, S., Kim, DH., Kim, Y., et al.[2017]

In a study of 54 girls with central precocious puberty, monthly injections of leuprolide acetate (3.75 mg) effectively suppressed luteinizing hormone (LH) levels in 96.3% of participants after 24 weeks, indicating strong efficacy in managing hormone levels.

The treatment also significantly reduced the ratio of bone age to chronological age and improved Tanner stage ratings, demonstrating both safety and effectiveness in slowing physical development associated with precocious puberty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter clinical trial of leuprolide acetate depot (Luphere depot 3.75 mg) for efficacy and safety in girls with central precocious puberty. Kim, YJ., Lee, HS., Lee, YJ., et al.[2022]

Loteprednol etabonate (LE) ophthalmic gel 0.5% maintains consistent drug concentrations regardless of whether the bottle is shaken before use, achieving a mean concentration of 102% of the declared amount over a 2-week period.

In contrast, both Prednisolone acetate suspensions showed significant variability in drug concentrations when not shaken, which could lead to under- or overdosing, potentially affecting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose uniformity of loteprednol etabonate ophthalmic gel (0.5%) compared with branded and generic prednisolone acetate ophthalmic suspension (1%). Marlowe, ZT., Davio, SR.[2021]

In a study involving 243 prostate cancer patients, the 1- and 3-month leuprorelin acetate depot formulations significantly reduced prostate-specific antigen levels by 95% and testosterone levels by 94% after a median follow-up of 132 days, indicating strong efficacy in managing advanced prostate cancer.

The treatment was well tolerated, with 90% of physicians rating the overall safety and tolerability as good or excellent, despite 37.86% of patients experiencing some treatment-emergent adverse events, primarily related to injection sites and hot flushes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of 1- and 3-month leuprorelin acetate depot formulations (Eligard(®)/Depo-Eligard(®)) for advanced prostate cancer in daily practice: a Belgian prospective non-interventional study. Braeckman, J., Michielsen, D.[2021]

In a 36-month study involving 72 children with central precocious puberty, leuprolide acetate 3-month depot (11.25 mg and 30 mg) effectively maintained suppression of luteinizing hormone (LH) levels, indicating continued efficacy in managing CPP.

The safety profile of leuprolide acetate remained acceptable over the long term, with no serious adverse events leading to discontinuation, and the most common side effect being mild injection site pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

36-month treatment experience of two doses of leuprolide acetate 3-month depot for children with central precocious puberty. Lee, PA., Klein, K., Mauras, N., et al.[2019]

In a study involving 105 children undergoing cataract surgery, loteprednol etabonate (LE) gel 0.5% was found to be as effective as prednisolone acetate (PA) 1% in reducing inflammation post-surgery, with no significant differences in inflammation scores observed.

Both treatments were safe, with no significant side effects or increases in intraocular pressure, indicating that LE gel 0.5% is a viable alternative to PA 1% for managing inflammation in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loteprednol etabonate gel 0.5% vs prednisolone acetate suspension 1% for the treatment of inflammation after cataract surgery in children. Vittitow, JL., Williams, JI.[2021]

In a study involving 54 subjects with central precocious puberty (CPP), all doses of leuprolide acetate effectively suppressed puberty over a 2-year period, indicating its efficacy as a treatment.

The 11.25 mg 3-month depot formulation resulted in higher levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) compared to the other doses, suggesting that higher dosing may be necessary for optimal hormonal control in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of 1- and 3-month depot leuprolide doses in the treatment of central precocious puberty. Fuld, K., Chi, C., Neely, EK.[2013]

In a study involving 21 healthy dogs, loteprednol etabonate (LE) ophthalmic drops caused significantly less suppression of cortisol levels compared to prednisolone acetate (PA) after 2 weeks of treatment, indicating a safer profile for the hypothalamic-pituitary-adrenal axis.

The results suggest that LE may be a preferable option for patients needing topical steroids, as it minimizes systemic glucocorticoid effects, making it suitable for cases where adrenocortical suppression should be avoided.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of ophthalmic loteprednol etabonate and prednisolone acetate effects on adrenocortical response to ACTH in dogs. Kline, KE., Walton, SA., Specht, AJ., et al.[2022]

Loteprednol etabonate ophthalmic gel 0.38% is effective in significantly reducing ocular inflammation and pain after cataract surgery, with complete resolution observed in more patients compared to a placebo by day 8, and pain relief noted as early as day 3.

The gel formulation has a lower incidence of treatment-related ocular adverse events (less than 1%) and does not significantly affect intraocular pressure or visual acuity, making it a safe option for post-operative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38%: A Review in Post-Operative Inflammation and Pain Following Ocular Surgery. Kang, C., Keam, SJ., Shirley, M., et al.[2021]

In a 96-week study involving 167 premenopausal women with hormone receptor-positive breast cancer, the 6-month depot formulation of leuprorelin acetate (TAP-144-SR 6M) demonstrated non-inferiority to the 3-month formulation (TAP-144-SR 3M) in suppressing serum estradiol levels, achieving suppression rates of 97.6% and 96.4%, respectively.

Both formulations were well tolerated, with common side effects like hot flushes and mild injection site reactions, all of which were of ≤Grade 2 severity, indicating a favorable safety profile for both treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of leuprorelin acetate 6-month depot, TAP-144-SR (6M), in combination with tamoxifen in postoperative, premenopausal patients with hormone receptor-positive breast cancer: a phase III, randomized, open-label, parallel-group comparative study. Kurebayashi, J., Toyama, T., Sumino, S., et al.[2022]

Citations

1.

frontiersin.org

frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1390674/full

Effectiveness of leuprolide acetate administered monthly ...

Conclusion: The 3-monthly treatment showed greater hormonal and growth suppression effects, but there was no significant difference in PAH ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3159140/

Efficacy of Leuprolide Acetate 1-Month Depot for Central ...

Treatment of CPP with leuprolide acetate 1-month depot had beneficial effects on growth rate and preservation of AH.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3062984/

Leuprolide Acetate 1-Month Depot for Central Precocious ...

During posttreatment follow-up (3.5 ± 2.2 years), all patients achieved a pubertal hormonal response within 1 year and menses were reported in all females ≥12 ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03695237

NCT03695237 | A Study to Evaluate Leuprolide Acetate 45 ...

The primary objective of the study is to assess the safety and efficacy of a leuprolide acetate (LA) 45 mg 6-month depot formulation for the treatment of CPP ...

5.

mdpi.com

mdpi.com/2227-9067/12/6/712

Long-Term Efficacy and Safety of Leuprorelin Treatment in ...

Conclusions: Leuprorelin treatment does not affect BMI or the onset of menstrual puberty in the long term, but has positive effects on adult height for children ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10274571/

Efficacy and Safety of Leuprolide Acetate 6-Month Depot for ...

Six-month intramuscular LA depot demonstrated 48-week efficacy with a safety profile consistent with other GnRH agonist formulations.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00667446

Safety Extension Study Of Leuprolide Acetate (Lupron ...

The purpose of this extension study is to determine if leuprolide acetate (11.25 mg and 30 mg) is safe in treating children with Central Precocious Puberty over ...

8.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37334213/

Efficacy and Safety of Leuprolide Acetate 6-Month Depot ...

Six-month intramuscular LA depot demonstrated 48-week efficacy with a safety profile consistent with other GnRH agonist formulations.