A Phase 2 Study of Vosoritide in Children With Idiopathic Short Stature

BioMarin Pharmaceutical

Status and phase: Enrolling; Phase 2

Conditions: Idiopathic Short Stature

Treatments: Drug: Human Growth Hormone; Drug: Placebo; Drug: Vosoritide Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT06382155

111-210

Details and patient eligibility

About

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).

Full 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

Enrollment: 100 estimated patients

Sex: All

Ages: 3 to 11 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100 participants in 5 patient groups, including a placebo group

Vosoritide Dose 1 - Low Dose

Experimental group

Description:

Vosoritide Dose 1 daily injection

Treatment:

Drug: Vosoritide Injection

Vosoritide Dose 2 - Medium Dose

Experimental group

Description:

Vosoritide Dose 2 daily injection

Treatment:

Drug: Vosoritide Injection

Vosoritide Dose 3 - High Dose

Experimental group

Description:

Vosoritide Dose 3 daily injection

Treatment:

Drug: Vosoritide Injection

Placebo

Placebo Comparator group

Description:

Placebo daily injection

Treatment:

Drug: Placebo

Human Growth Hormone

Active Comparator group

Description:

hGH daily injection (US only)

Treatment:

Drug: Human Growth Hormone