Efficacy, Safety, and Pharmacokinetics of Leuprolide Mesylate in Subjects With Central Precocious Puberty

An Open-label, Single Arm, Multicenter, Phase III Study on the Efficacy, Safety, and Pharmacokinetics of FP-001 42 mg Controlled Release in Patients With Central (Gonadotropin-Dependent) Precocious Puberty (Casppian Study)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Puberty; Precocious, Central
• Intervention / Treatment: Drug: Leuprolide Mesylate, Subcutaneous injection of 42 mg Leuprolide

Detailed Description

This is a multi-center, open-label, single-arm study. All subjects will be pediatric patients with central precocious puberty judged to be candidates for GnRH (gonadotropin releasing hormone) analog therapy, and all will receive two injections of FP-001 42 mg six-month apart in an unblinded fashion.

• Study Type: Interventional
• Enrollment (Estimated): 93
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Children's Hospital, Capital Medical University
  • Shanghai, China
    • Children's Hospital of Shanghai
  • Shanghai, China
    • Children's Hospital of Fudan University
  • Shanghai, China
    • Shanghai Children's Medical Center
  • Tianjin, China
    • Tianjin Medical University General Hospital
  • Anhui
    • Hefei, Anhui, China
      • The Second Hospital of Anhui Medical University
  • Chaoyang District
    • Beijing, Chaoyang District, China
      • Children's Hospital affiliated to Capital Institute of Pediatrics
  • Fujian
    • Xiamen, Fujian, China
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
    • Guangzhou, Guangdong, China
      • The Third Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China
      • Pearl River Hospital, Southern Medical University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College of HUST
    • Wuhan, Hubei, China
      • Wuhan Children's Hospital, Tongji Medical College of HUST
  • Hunan
    • Changsha, Hunan, China
      • Hunan Children's Hospital
  • Jiangsu
    • Suzhou, Jiangsu, China
      • Children's Hospital of Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Jiangxi Provincial Children's Hospital
  • Jilin
    • Changchun, Jilin, China
      • The First Bethune Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China
      • Shengjing Hospital of China Medical University
  • Shanxi
    • Taiyuan, Shanxi, China
      • Children's Hospital of Shanxi
  • Sichuan
    • Chengdu, Sichuan, China
      • Chengdu Women's and Children's Central Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The Children's Hospital, Zhejiang University School of Medicine
    • Jiaxing, Zhejiang, China
      • The First Hospital of Jiaxing Affiliated Hospital of Jiaxing University
    • Ningbo, Zhejiang, China
      • Ningbo Women & Children's Hospital
• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • University Pediatric Hospital
• Taiwan
  • Changhua, Taiwan, 50006
    • Changhua Christian Hospital
  • Kaohsiung City, Taiwan, 704302
    • Chang Gung Memorial Hospital-Kaohsiung Branch
  • Taichung, Taiwan
    • China Medical University Hospital
  • Tainan City, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 104217
    • Mackay Memorial Hospital
  • Taoyuan, Taiwan, 333423
    • LinKou Chang-Gung Memorial Hospital (CGMH-LK)
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Arizona University
  • California
    • San Diego, California, United States, 92123
      • Rady Children's Hospital- San Diego
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Health Center
    • St. Petersburg, Florida, United States, 33701
      • Johns Hopkins - All Children's Hospital
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Clinical Research
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Fort Worth, Texas, United States, 76104
      • Cook Children's
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Virginia University
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 9 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Females aged 2 to 8 years (inclusive) or males aged 2 to 9 years (inclusive).
2. Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have not received prior GnRHa treatment for CPP.
3. Pubertal-type LH response at 60 minutes post GnRHa stimulation test before treatment initiation > 5 mIU/mL.
4. Clinical evidence of puberty, defined as Tanner stage ≥ 2 for breast development in females or testicular volume ≥ 4 mL in males.
5. Willing and able to participate in the study.
6. Difference between bone age (Greulich and Pyle method) and chronological age ≥ 1 year.
7. Bone age < 13 years for girls and < 14 years for boys.
8. 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).
9. Signed Assent by patients as per IRB/IEC requirements.

Exclusion Criteria:

1. Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion. This includes true CPP triggered by other conditions, such as congenital adrenal hyperplasia.
2. Prior or current GnRH treatment for CPP.
3. Non-progressing isolated premature thelarche.
4. Presence of an unstable intracranial tumor or an intracranial tumor requiring neurosurgery or cerebral irradiation. Patients with hamartomas or adenomas not requiring surgery are eligible.
5. Any other condition, chronic illness or treatment that, in the opinion of the Investigator, may interfere with growth or other study endpoints (e.g., chronic steroid use [except mild topical steroids], renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumor).
6. Prior or current therapy with medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1).
7. Major medical or psychiatric illness that could interfere with study visits.
8. Diagnosis of short stature (i.e., 2.25 standard deviations (SD) below the mean height for age).
9. Positive urine pregnancy test.
10. Known hypersensitivity to GnRH or related compounds.
11. Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the patients to participate in the study.
12. Any other condition(s) which could significantly interfere with Protocol compliance.
13. Treatment with an investigational product within 5 half-lives of that product in prior clinical studies before the baseline visit (Day 0).
14. Known history of seizures, epilepsy, and/or central nervous system disorders that may be associated with seizures or convulsions.
15. Prior (within 6 months of Baseline (Day 0)) or current use of medications that, per Investigator opinion, have been associated with seizures or convulsions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FP-001 42 mg; 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).	Drug: Leuprolide Mesylate, Subcutaneous injection of 42 mg Leuprolide; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Leuprolide Mesylate (FP-001 42 mg)	The percentage of patients with serum LH concentrations < 4 mIU/mL 60 minutes following an abbreviated GnRHa stimulation test at Visit 6 (Week 24).	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of FP-001 42 mg on bone age progression	Evaluate the changes in bone age progression from the baseline to Weeks 24 and 48 using centralized analysis of wrist x-ray	24 and 48 weeks
Effect of FP-001 42 mg on growth rate	Evaluate the changes in growth rate and bone age advancement relative to chronological age from baseline to end of study using height in meters	48 weeks
Effect of FP-001 42 mg on physical signs of puberty	Evaluate the change in physical signs of puberty as measure by Tanner stages from baseline to end of study	48 weeks
Effect of FP-001 42 mg on suppression of physical signs of puberty	Evaluate the percentage of patients with suppression of physical signs of puberty	48 weeks
Acute-On-Chronic (AOC) phenomenon of serum testosterone and LH	Evaluate The proportion of subjects exhibiting "acute-on-chronic" phenomenon (i.e., related to the second dose of FP-001 42 mg)	48 weeks

Collaborators and Investigators

• Sponsor: Foresee Pharmaceuticals Co., Ltd.
• Collaborators: QPS Holdings LLC; Changchun GeneScience Pharmaceutical Co., Ltd.
• Investigators: Study Director: Bassem Elmankabadi, Foresee Pharma

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2023
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: August 4, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 9, 2022

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Gonadotropin-Releasing Hormone; Leuprolide
• Other Study ID Numbers: FP-001-CP-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No