Clinical trial NCT02452931: Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty
Official title: An Open-label, Single Arm, Multicenter Study on the Efficacy, Safety, and Pharmacokinetics of Leuprolide Acetate 45 mg for Injectable Suspension Controlled Release in Subjects With Central (Gonadotropin-Dependent) Precocious Puberty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Precocious Puberty, Central
Lead sponsor: Tolmar Inc.
Sponsor class: INDUSTRY
First posted: 2015-05-25
Enrollment: 64
Sex: ALL
Minimum age (years): 2
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study determines the effectiveness of leuprolide acetate 45 mg for injectable suspension for treatment of children with Central Precocious Puberty.

Detailed description: Leuprolide acetate is a GnRH agonist that inhibits pituitary gonadotropin secretion by binding to the GnRH receptors and blocking downstream hormone synthesis. The steady decrease in hormone synthesis (LH and FSH) leads to a suppression of testicular and ovarian steroidogenesis. In children with CPP, this steady decrease in hormone synthesis disrupts the progression of puberty.

Eligibility criteria: Inclusion Criteria:

* Females age 2 to 8 years (inclusive) or males age 2 to 9 years (inclusive)
* Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have not received prior GnRH agonist treatment for CPP
* Pubertal-type LH response following an abbreviated GnRHa stimulation test before treatment initiation
* Clinical evidence of puberty, defined as Tanner stage ≥ 2 for breast development in females or testicular volume ≥ 4 mL in males
* Difference between bone age (Greulich and Pyle method) and chronological age ≥ 1 year

Exclusion Criteria:

* Gonadotropin-independent (peripheral) precocious puberty
* Prior or current GnRH treatment for CPP
* Prior or current therapy with medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1)
* Diagnosis of short stature (ie, 2.25 standard deviations (SD) below the mean height for age)
* Known history of seizures, epilepsy, and/or central nervous system disorders that may be associated with seizures or convulsions
* Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study

Primary outcomes:
measure: Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months.
timeFrame: 6 months
Secondary outcomes:
measure: Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels.
timeFrame: Week 12, Week 24, Week 36, and Week 48
measure: Changes in Height Velocity (Growth Rate)
timeFrame: Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
measure: Bone Age Ratio to Chronological Age at Time of Measurement
timeFrame: Week 24 and Week 48
measure: Percent Change From Baseline in Height
timeFrame: Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
measure: Tanner Scores: Boys - Development of External Genitalia
timeFrame: Baseline, Week 12, Week 24, Week 36, and Week 48
measure: Tanner Scores: Boys - Development of External Genitalia (Change From Baseline)
timeFrame: Week 12, Week 24, Week 36, and Week 48
measure: Tanner Scores: Boys and Girls - Pubic Hair
timeFrame: Baseline, Week 12, Week 24, Week 36, and Week 48
measure: Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline)
timeFrame: Week 12, Week 24, Week 36, and Week 48
measure: Tanner Scores: Girls - Breast Development
timeFrame: Baseline, Week 12, Week 24, Week 36, and Week 48
measure: Tanner Scores: Girls - Breast Development (Change From Baseline)
timeFrame: Week 12, Week 24, Week 36, and Week 48
Other outcomes:
measure: Height
timeFrame: Screening, Baseline, Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
measure: Bone Age
timeFrame: Baseline, Week 24, and Week 48
measure: Bone Age Progression
timeFrame: Week 24 and Week 48
measure: Bone Age Ratio to Chronological Age at Time of Measurement (Percent Change From Baseline)
timeFrame: Week 24 and Week 48
measure: Bone Age Ratio to Chronological Age at Start of Study (Percent Change From Baseline)
timeFrame: Week 24 and Week 48
measure: Bone Age Ratio to Chronological Age at Start of Study
timeFrame: Baseline, Week 24, and Week 48
measure: GnRH Antagonist Evaluation
timeFrame: Week 2, Week 4, Week 12, Week 20, Week 24, Week 26, Week 36, Week 44, and Week 48
measure: Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels.
timeFrame: Week 12, Week 24, Week 36, and Week 48
measure: Changes in the Ratio of LH/FSH
timeFrame: Screening (Pre&Post GnRHa Stim Test), Baseline (0,1,4,6 hours Post-Injection), Week 4, Week 12 (Pre&Post GnRHa Stim Test), Week 20, Week 24 (Pre&Post GnRHa Stim Test), Week 36 (Pre&Post GnRHa Stim Test), Week 44, and Week 48 (Pre&Post GnRHa Stim Test)
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Hollywood
country: United States
facility: Joe DiMaggio Children's Hospital
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center, Endocrine
state: Ohio
city: Tulsa
country: United States
facility: University of Oklahoma College of Medicine
state: Oklahoma
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research and Innovation
state: Washington
city: Buenos Aires
country: Argentina
facility: Hospital de Ninos
city: Calgary
country: Canada
facility: University of Calgary, Alberta Children's Hospital
state: Alberta
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile
state: Metropolitana
city: Santiago
country: Chile
facility: Instituto de Investigaciones Materno Infantil (IDIMI)
state: Metropolitana
city: Antofagasta
country: Chile
facility: Hospital Regional de Antofagasta Leonardo Guzman
state: Second Region
city: Monterrey
country: Mexico
facility: Hospital Unversitario "Dr. Jose Eleuterio Gonzalez"
state: Nuevo Leon
city: Durango
country: Mexico
facility: Instituto de Investigaciones Aplicadas a la Neurociencia, A.C.
city: Auckland
country: New Zealand
facility: The Liggins Institute, University of Auckland
Study officials:
affiliation: orphan reach USA, LLC
name: Peggy Schorr
role: STUDY_DIRECTOR
References:
citation: Klein KO, Freire A, Gryngarten MG, Kletter GB, Benson M, Miller BS, Dajani TS, Eugster EA, Mauras N. Phase 3 Trial of a Small-volume Subcutaneous 6-Month Duration Leuprolide Acetate Treatment for Central Precocious Puberty. J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3660-71. doi: 10.1210/clinem/dgaa479.