Vosoritide for Selected Genetic Causes of Short Stature (NCT04219007) | Clinical Trial Compass
Active — Not RecruitingPhase 2
Vosoritide for Selected Genetic Causes of Short Stature
United States56 participantsStarted 2020-08-04
Plain-language summary
Short stature can be caused by a number of genetic etiologies, many of which directly affect the growth plate. The FGFR3/CNP pathway is central to growth of the chondrocyte. The study team hypothesizes that patients with selected genetic causes of short stature that interact with this pathway will benefit from treatment with vosoritide, a CNP analog, a selective NPR-B agonist which directly targets the growth plate. This study will enroll patients with short stature in selected genetic categories and will follow them for a 6 month observation period to obtain a baseline growth velocity, safety profile and quality of life assessment. Patients will then be treated with vosoritide for 12 months and will be assessed for safety monitoring and improvement in height outcomes.
Who can participate
Age range3 Years – 10 Years
SexALL
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Inclusion criteria
✓. Parent(s) or guardian(s) are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any research-related procedure. Also, subjects under the age of 18 are willing and able to provide assent (if required) after the nature of the study has been explained and prior to performance of any research-related procedure.
✓. Stated willingness to comply with all study procedures and availability for the duration of the study
✓. Age \>3 years 0 days AND \<10 years 364 days for males, \<9 years 364 days for females
✓. Pre-pubertal defined as Tanner Stage 1 breasts in females and testicular volumes \<3 cc in males. This must be confirmed at the Day 1 visit prior to initiation of vosoritide.
✓. Patient height \<-2.25 SDS. All height SDS values are calculated using the CDC growth charts/data tables (Center for Disease Control and Prevention, 2000).
✓. Patients with pathogenic or likely pathogenic variants in genes known to cause the specific genetic subgroups of short stature listed below are eligible for inclusion in the study. Pathogenicity of variants will be classified as per the American College of Medical Genetics criteria with the exception of ACAN mutations as detailed below (Richards et al., 2015). Documentation of the presence of the variant must be obtained using a lab results report from a CLIA certified laboratory. Classification of the variant's pathogenicity status will be performed by the Children's National study team.
What they're measuring
1
Incidence of Treatment Emergent Adverse Events [Safety and Tolerability]
Timeframe: 12 months
2
Incidence of Symptomatic Hypotension events [Safety and Tolerability]
Timeframe: 12 months
3
Change from Baseline in annualized growth velocity
✓. A heterozygous deletion of the entire gene or of \>1 complete exons of the gene
✓. Any truncating mutation including frameshift, nonsense, splice site mutations within 2 bases of the exon/intron boundary, and start loss variants
Exclusion criteria
✕. Growth plate fusion - Defined as a bone age via the Greulich and Pyle method of 13 years in females and 15 years in males. These patients have limited remaining growth potential.
✕. Concomitant treatment with growth hormone or recombinant IGF-1. Patients may have been previously treated with growth hormone or IGF-1 therapy. If the patient is currently on one of these therapies, they will be required to discontinue treatment in order to begin the baseline observation period for this trial. That decision will be deferred to their treating clinical endocrinologists in conjunction with the patient's guardians. We anticipate that only patients who are having a poor response to their therapy will be interested in enrolling in the current study as there is no rationale for a patient who is receiving growth hormone therapy and having a positive response to enroll in the current study.
✕. Prior treatment with a GnRH analog, aromatase inhibitor or oxandrolone
✕. History of any type of malignancy
✕. Chronic medical condition known to affect growth including but not limited to:
✕. Malnutrition - Defined as a BMI \<5th percentile (CDC growth charts)
✕. Any clinically significant abnormality on screening tests as determined by the principal investigator. Abnormal screening labs may be repeated during the 6 month observation period prior to Day 1. If they return to normal or non-clinically significant deviations per the PI's determination, the subject may proceed with the study.
✕. Known or suspected allergy to trial medication, excipients, or related products