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).
Brief Title
A Phase 2 Study of Vosoritide in Children with Idiopathic Short Stature
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
+1 415.475.5852
Central Contact Email
medinfo@bmrn.com
Completion Date
Completion Date Type
Estimated
Conditions
Idiopathic Short Stature
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
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
Inclusion 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
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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
10 Years
Minimum Age
3 Years
NCT Id
NCT06382155
Org Class
Industry
Org Full Name
BioMarin Pharmaceutical
Org Study Id
111-210
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 2, Randomized, Controlled, Multicenter Study of Vosoritide in Children with Idiopathic Short Stature
Primary Outcomes
Outcome Measure
Change from baseline in Annualized Growth Velocity (AGV)
Outcome Time Frame
At 6 months
Outcome Measure
Change from baseline in height
Outcome Time Frame
At 4 years
Outcome Measure
Change from baseline in height Z-score
Outcome Time Frame
At 4 years
Secondary Outcomes
Outcome Time Frame
Until the end of the study, up to 15 years
Outcome Measure
Incidence of treatment-emergent adverse events
Outcome Time Frame
At 6 months
Outcome Measure
Change from baseline in AGV Z-score (average stature reference)
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Change from baseline in height
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Change from baseline in height Z score
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Change from baseline at prespecified timepoints in urine cyclic guanine monophosphate (cGMP)
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Change from baseline at pre-specified timepoints in serum collagen X marker (CXM)
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Change from baseline in bone age minus chronological age at pre-specified timepoints
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Change from baseline in total body (less head) bone mineral density (BMD) Z-score
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Change from baseline in lumbar spine BMD Z-score
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Change from baseline in total body (less head) bone mineral content (BMC)
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Change from baseline in lumbar spine BMC
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Maximum concentration (Cmax) of vosoritide in plasma
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Area under the plasma vosoritide concentration time-curve from time 0 to infinity (AUC0-∞)
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Area under the plasma vosoritide concentration time-curve from time 0 to the last measurable concentration (AUC0-t)
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Elimination half-life of vosoritide (t½)
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Apparent clearance of vosoritide
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Apparent volume of distribution of vosoritide based upon the terminal phase (Vz/F)
Outcome Time Frame
Every 6 months through the end of study, up to 15 years
Outcome Measure
Time vosoritide is present at maximum concentration (Tmax)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
10
Minimum Age Number (converted to Years and rounded down)
3
Investigators
Investigator Type
Principal Investigator
Investigator Name
Laurie Cohen
Investigator Email
lacohen@montefiore.org