Clinical trial NCT06382155: A Phase 2 Study of Vosoritide in Children with Idiopathic Short Stature
Official title: A Phase 2, Randomized, Controlled, Multicenter Study of Vosoritide in Children with Idiopathic Short Stature
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Idiopathic Short Stature
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2024-04-24
Enrollment: 100
Sex: ALL
Minimum age (years): 3
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate i) the effect of multiple doses of vosoritide and ii) the effect of the therapeutic dose of vosoritide compared to human growth hormone (hGH), in children with idiopathic short stature (ISS).

Detailed description: Following a minimum 6 month observational period in which baseline growth is assessed, participants in the vosoritide and placebo groups will complete a minimum of 6 months of randomized treatment (maximum of 6 months of placebo treatment), followed by open-label treatment with vosoritide until they reach near-final adult height, or at least 16 years of age for females or 18 years of age for males, whichever comes later. Participants randomized to the hGH group will receive open-label hGH for a minimum of 4 years.

Eligibility criteria: Key Inclusion Criteria:

1. Height assessment corresponding to a height Z-score of ≤ -2.25 SDs in reference to the general population of the same age and sex, as calculated using the Centers for Disease Control and Prevention (CDC) growth charts
2. Tanner Stage 1, at time of signing the ICF (unless too young to stage).

Key Exclusions:

1. Known chromosomal imbalance or genetic variant causing short stature syndrome, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, Turner syndrome, disproportionate skeletal dysplasias, abnormal SHOX gene analysis, or Rasopathy (including Noonan syndrome)
2. Previous treatment with a growth promoting agent

Primary outcomes:
measure: Change from baseline in Annualized Growth Velocity (AGV)
timeFrame: At 6 months
measure: Change from baseline in height
timeFrame: At 4 years
measure: Change from baseline in height Z-score
timeFrame: At 4 years
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: Until the end of the study, up to 15 years
measure: Change from baseline in AGV Z-score (average stature reference)
timeFrame: At 6 months
measure: Change from baseline in height
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Change from baseline in height Z score
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Change from baseline at prespecified timepoints in urine cyclic guanine monophosphate (cGMP)
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Change from baseline at pre-specified timepoints in serum collagen X marker (CXM)
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Change from baseline in bone age minus chronological age at pre-specified timepoints
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Change from baseline in total body (less head) bone mineral density (BMD) Z-score
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Change from baseline in lumbar spine BMD Z-score
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Change from baseline in total body (less head) bone mineral content (BMC)
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Change from baseline in lumbar spine BMC
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Maximum concentration (Cmax) of vosoritide in plasma
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Area under the plasma vosoritide concentration time-curve from time 0 to infinity (AUC0-∞)
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Area under the plasma vosoritide concentration time-curve from time 0 to the last measurable concentration (AUC0-t)
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Elimination half-life of vosoritide (t½)
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Apparent clearance of vosoritide
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Apparent volume of distribution of vosoritide based upon the terminal phase (Vz/F)
timeFrame: Every 6 months through the end of study, up to 15 years
measure: Time vosoritide is present at maximum concentration (Tmax)
timeFrame: Every 6 months through the end of study, up to 15 years
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Center Of Excellence in Diabetes and Endocrinology
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation (LA BioMed)
state: California
city: Pensacola
country: United States
facility: Nemours Children's Health System - Corporate Headquarters
state: Florida
city: Columbus
country: United States
facility: Centricity Research
state: Georgia
city: Boise
country: United States
facility: St. Luke's Children's Endocrinology
state: Idaho
city: Idaho Falls
country: United States
facility: Rocky Mountain Clinical Research - Idaho Falls
state: Idaho
city: Bronx
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: Buffalo
country: United States
facility: UBMD Pediatrics
state: New York
Study officials:
affiliation: BioMarin Pharmaceutical
name: Medical Director MD
role: STUDY_DIRECTOR
References: