A Study to Evaluate Leuprolide Acetate 45 mg 6-Month Formulation in Children With Central Precocious Puberty (CPP)

A Phase 3, Multicenter, Open-Label, Two-Part Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Leuprolide Acetate 45 mg 6-Month Depot Formulation in Children With Central Precocious Puberty (CPP)

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 in children who are either naïve to treatment with a gonadotropin-releasing hormone agonist (GnRHa) or who have been previously treated with a GnRHa.

Study Overview

• Status: Completed
• Conditions: Central Precocious Puberty (CPP)
• Intervention / Treatment: Drug: Leuprolide Acetate (LA)

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • Pediatric Endocrine Research Associates /ID# 200131
• United States
  • California
    • Long Beach, California, United States, 90806-1651
      • Pediatric Endocrinology Associates /ID# 200629
    • San Diego, California, United States, 92123
      • Rady Children's Hospital San Diego /ID# 202491
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado /ID# 201645
    • Greenwood Village, Colorado, United States, 80111
      • Pediatric Endocrine Associates /ID# 201089
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Health System /ID# 201331
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Hospital /ID# 201624
  • Georgia
    • Atlanta, Georgia, United States, 30318-2508
      • Van Meter Pediatric Endocrinology /ID# 201688
  • Idaho
    • Idaho Falls, Idaho, United States, 83404-7596
      • Rocky Mountain Diabetes and Osteoporosis Center /ID# 209878
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University /ID# 200526
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Pediatric Endocrine Associates /ID# 202396
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455-1450
      • University of Minnesota /ID# 200508
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Children's Mercy Hospital/ID# 200221
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135-2527
      • University of Oklahoma /ID# 200659
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-2360
      • Penn State Hershey Medical Ctr /ID# 200287
    • Philadelphia, Pennsylvania, United States, 19104-4319
      • Children's Hospital of Philadelphia - Main /ID# 203846
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Med. Center /ID# 212937
  • Washington
    • Tacoma, Washington, United States, 98405
      • Multicare Institute for Research and Innovation /ID# 202188

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children with CPP who are naïve to treatment with a gonadotropin-releasing hormone agonist (GnRHa) (females 2 - 8 years of age, or males 2 - 9 years of age) or who have been on standard GnRHa therapy for at least 6 months (females 2 - 10 years of age, or males 2 - 11 years of age).
• No history of clinically significant medical conditions or any other reason that the investigator determines would make the participant an unsuitable candidate to receive study drug.

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: Leuprolide Acetate (LA); Participants received leuprolide acetate (LA) 45 mg every 6 months administered as an intramuscular injection for up to 144 weeks.	Drug: Leuprolide Acetate (LA); Administered intramuscularly as an injection; Other Names: Lupron Depot

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Suppression of Peak Gonadotropin-releasing Hormone Agonist (GnRHa)-Stimulated Luteinizing Hormone (LH) to Less Than 4 mlU/mL at Week 24	Suppression of GnRHa-stimulated luteinizing hormone (LH) was measured using a peak GnRHa stimulation test, performed using subcutaneous injection with an aqueous formulation of leuprolide acetate at 20 µg/kg. Peak stimulated LH was calculated by taking the maximum LH concentrations measured from blood samples taken at 30 or 60 min following the GnRHa stimulation test. Suppression of GnRHa-stimulated luteinizing hormone is defined as peak stimulated LH less than 4 mIU/mL.	Week 24 (prior to the Week 24 dose); samples for LH measurement were taken 30 and 60 minutes after the stimulation test injection.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Percentage of Participants With Suppression of Peak GnRHa-stimulated LH to Less Than 4 mlU/mL at Weeks 12, 20, 44, and 48	Suppression of GnRHa-stimulated luteinizing hormone (LH) was measured using a peak GnRHa stimulation test, performed using subcutaneous injection with an aqueous formulation of leuprolide acetate at 20 µg/kg. Peak stimulated LH was calculated by taking the maximum LH concentrations measured from blood samples taken at 30 or 60 min following the GnRHa stimulation test. Suppression of GnRHa-stimulated luteinizing hormone is defined as peak stimulated LH less than 4 mIU/mL.	Weeks 12, 20, 44, and 48 (prior to Week 48 dose); samples for LH measurement were taken 30 and 60 minutes after the stimulation test injection.
Part 1: Percentage of Female Participants With Suppression of Basal Estradiol to < 20 pg/mL at Weeks 12, 20, 24, 44, and 48	Estradiol concentrations were measured from blood samples taken at each study visit prior to stimulation testing (and prior to study drug administration at Weeks 24 and 48).	Weeks 12, 20, 24, 44, and 48
Part 1: Percentage of Male Participants With Suppression of Basal Testosterone to < 30 ng/dL at Weeks 12, 20, 24, 44, and 48	Testosterone concentrations were measured from blood samples taken at each study visit prior to stimulation testing (and prior to study drug administration for Weeks 24 and 48).	Weeks 12, 20, 24, 44, and 48
Parts 1 and 2: Percentage of Participants With Suppression of the Physical Signs of Puberty	Breast development in females and testicular volume or genital development in males was assessed using modified Tanner staging, on a scale from Stage 1 (prepubertal) to Stage 5 (adult characteristics). Females: Suppression is defined as regression or no progression of breast development according to modified Tanner staging. Males: Suppression is defined as regression or no progression in testicular volume and genital staging according to modified Tanner staging.	Part 1: Weeks 24 and 48; Part 2: Weeks 72, 96, 120, and 144
Parts 1 and 2: Change From Baseline in Incremental Growth Rate	Growth rate (height in centimeter/year) was calculated both prior to treatment in the study and during the study. For Baseline calculation a historical measurement of height at least 6 months prior to Screening and the Screening value was used.	Part 1: Baseline and Weeks 4, 12, 20, 24, 44, and 48; Part 2: Weeks 72, 96, 120, and 144
Parts 1 and 2: Ratio of Change From Baseline in Bone Age to Change From Baseline in Chronological Age	Bone age was assessed from radiographs of the hand and wrist by a central imaging vendor using the BoneXpert automated system. A ratio less than 1 indicates less advancement of bone age compared to chronological age.	Part 1: Baseline and Weeks 24 and 48; Part 2: Weeks 72, 96, 120, and 144
Part 2: Percentage of Participants With Maintenance of Suppression of GnRHa-stimulated LH (< 4 mlU/mL)	Suppression of GnRHa-stimulated luteinizing hormone (LH) was measured using a peak GnRHa stimulation test, performed using subcutaneous injection with an aqueous formulation of leuprolide acetate at 20 µg/kg. Peak stimulated LH was calculated by taking the maximum LH concentrations measured from blood samples taken at 30 or 60 min following the GnRHa stimulation test. Suppression of GnRHa-stimulated luteinizing hormone is defined as peak stimulated LH less than 4 mIU/mL.	Weeks 72, 96, 120, and 144
Part 2: Percentage of Female Participants With Maintenance of Suppression of Basal Estradiol to < 20 pg/mL	Estradiol concentrations were measured from blood samples taken at each study visit prior to stimulation testing.	Weeks 72, 96, 120, and 144
Part 2: Percentage of Male Participants With Maintenance of Suppression of Basal Testosterone to < 30 ng/dL	Male participants with maintenance of suppression of testosterone to < 30 ng/dL are assessed	Weeks 72, 96, 120, and 144

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2018
• Primary Completion (Actual): May 6, 2021
• Study Completion (Actual): November 29, 2023

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: October 2, 2018
• First Posted (Actual): October 4, 2018

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Central Precocious Puberty (CPP); Leuprolide Acetate (LA)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: M16-904

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

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