Leuprolide for Precocious Puberty

Recruiting at 41 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

93 Participants Needed

Trial Summary

What is the purpose of this trial?

The study will evaluate if Leuprolide Mesylate is safe and effective in the treatment of subjects with central (gonadotropin-dependent) precocious puberty, when administered as two injections six months apart.

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.

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

Research shows that leuprolide acetate, a form of the drug, is effective and safe for treating children with central precocious puberty, as demonstrated in studies with both short-term and long-term treatment experiences. ^{1 2 3 4 5}

Is leuprolide safe for treating precocious puberty?

Leuprolide has been shown to be generally safe in humans, with studies indicating it is well tolerated in both children with precocious puberty and adults with prostate cancer. No serious adverse effects were observed in these studies. ^{1 2 3 4 6}

How is the drug Leuprolide Mesylate unique in treating precocious puberty?

Leuprolide Mesylate is unique because it works by suppressing the hormones that trigger early puberty, effectively delaying its onset. It is administered as an injection, which can be more convenient for maintaining consistent hormone levels compared to daily oral medications. ^{7 8 9 10 11}

Research Team

Susan Whitaker

Principal Investigator

Foresee Pharma

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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]

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 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]

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 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]

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]

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]

References

1. England 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. [2017]

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

36-month treatment experience of two doses of leuprolide acetate 3-month depot for children with central precocious puberty. [2019]

3. Korea (South) 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. [2022]

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

A randomized trial of 1- and 3-month depot leuprolide doses in the treatment of central precocious puberty. [2013]

5. Japan 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. [2022]

6. Poland 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. [2021]

7. United States 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. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38%: A Review in Post-Operative Inflammation and Pain Following Ocular Surgery. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Comparison of ophthalmic loteprednol etabonate and prednisolone acetate effects on adrenocortical response to ACTH in dogs. [2022]

10. United States 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%. [2015]

11. New Zealand pubmed.ncbi.nlm.nih.gov

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