Idiopathic Short Stature
Conditions
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)(hGH; only in the United States), 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. A Treatment Completion visit will occur approximately 4 weeks after the last administration of investigational product. Participants who discontinue study treatment after ≥13 weeks of exposure may remain in the study and complete follow-up assessments per the protocol schedule (including annual and periodic assessments through End of Study). If a participant discontinues treatment and declines further participation, they will be asked to return for a final Treatment Completion and End of Study visit approximately 4 weeks after the last injection. Safety monitoring includes regular clinical and imaging assessments, including hip and lower-extremity evaluations, monitoring for hypotension, fractures, and slipped capital femoral epiphysis, with oversight by an independent Data Monitoring Committee An independent Data Monitoring Committee will periodically review safety data and may recommend treatment discontinuation based on predefined safety signals
Interventions
Experimental Drug Lyophilized powder for reconstitution
Commercial product containing somatotropin
DRUGPlacebo
Lyophilized powder for reconstitution
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 11 Years
Healthy volunteers
No
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. If participant is ≥ 5 years at Screening,must be Tanner Stage I to be eligible for enrollment and randomization3. Historic stimulation test result with serum or plasma GH level greater than 10 μg/L or serum IGF-1 in the normal range for age (≥ -1.00 SDs and ≤+2.00 SDs). 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), ACAN deficiency. 2. Previous treatment with a growth promoting agent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in Annualized Growth Velocity (AGV) | At 6 months |
| Change from baseline in height | At 4 years |
| Change from baseline in height Z-score | At 4 years |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events | Until the end of the study, up to 15 years |
| Change from baseline in Height Z-score (average stature reference) | At 6 months |
| Change from baseline in height | Every 6 months through the end of study, up to 15 years |
| Change from baseline in height Z score | Every 6 months through the end of study, up to 15 years |
| Change from baseline at prespecified timepoints in urine cyclic guanine monophosphate (cGMP) | Every 6 months through the end of study, up to 15 years |
| Change from baseline at pre-specified timepoints in serum collagen X marker (CXM) | Every 6 months through the end of study, up to 15 years |
| Change from baseline in bone age minus chronological age at pre-specified timepoints | Every 6 months through the end of study, up to 15 years |
| Change from baseline in whole body (less head) bone mineral density (BMD) Z-score | Every 6 months through the end of study, up to 15 years |
| Change from baseline in lumbar spine BMD Z-score | Every 6 months through the end of study, up to 15 years |
| Change from baseline in total body (less head) bone mineral content (BMC) | Every 6 months through the end of study, up to 15 years |
| Change from baseline in lumbar spine BMC | Every 6 months through the end of study, up to 15 years |
| Maximum concentration (Cmax) of vosoritide in plasma | Every 6 months through the end of study, up to 15 years |
| Area under the plasma vosoritide concentration time-curve from time 0 to infinity (AUC0-∞) | Every 6 months through the end of study, up to 15 years |
| Area under the plasma vosoritide concentration time-curve from time 0 to the last measurable concentration (AUC0-t) | Every 6 months through the end of study, up to 15 years |
| Elimination half-life of vosoritide (t½) | Every 6 months through the end of study, up to 15 years |
| Apparent clearance of vosoritide | Every 6 months through the end of study, up to 15 years |
| Apparent volume of distribution of vosoritide based upon the terminal phase (Vz/F) | Every 6 months through the end of study, up to 15 years |
| Time vosoritide is present at maximum concentration (Tmax) | Every 6 months through the end of study, up to 15 years |
Countries
Australia, France, Germany, Italy, South Korea, United States
Contacts
CONTACTTrial Specialist
STUDY_DIRECTORMedical Director MD
BioMarin Pharmaceutical
Outcome results
None listed