A Phase 2 Basket Study of Vosoritide in Children With Turner Syndrome, SHOX Deficiency and Noonan Syndrome With an Inadequate Response to Human Growth Hormone
- Conditions
- Short Stature Homeobox- Containing Gene SHOX DeficiencyNoonan SyndromeTurner Syndrome
- Interventions
- Registration Number
- NCT06668805
- Lead Sponsor
- BioMarin Pharmaceutical
- Brief Summary
The purpose of this basket study in children with Turner syndrome, SHOX deficiency, and Noonan syndrome is to evaluate the effect of 3 doses of vosoritide versus hGH on growth as measured by AGV after 6 months of treatment. The long-term efficacy and safety of vosoritide at the therapeutic dose will be evaluated up to FAH.
- Detailed Description
This is a Phase 2, randomized, active-controlled, multicenter, basket study of vosoritide in children with Turner syndrome, short stature homeobox-containing gene (SHOX) deficiency, or Noonan syndrome who have an inadequate response to human growth hormone (hGH) treatment. The study is intended to characterize the short-term efficacy and safety of 3 dosing regimens of vosoritide versus hGH. The efficacy and safety of the vosoritide therapeutic dose will be further evaluated, with a comparison to hGH after 2 years of treatment, and an analysis of the impact of vosoritide on final adult height (FAH).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 72
- Participants must be ≥ 3 years old, and < 10 years old (females) or < 11 years old (males),at the time of signing the informed consent form
- A genetically confirmed diagnosis of Turner syndrome, SHOX deficiency or Noonan syndrome.
- A height assessment corresponding to a height Z score of ≤ -2.00 SDs in reference to the general population of the same age and sex.
- Tanner Stage 1, at time of signing the ICF.
- Have been receiving continuous hGH for the treatment of short stature associated with their condition for a minimum of 1 year immediately prior to enrollment.
- Are willing to continue on hGH for the Baseline Growth Phase, and for 2 years post randomization if randomized to the hGH arm.
- Inadequate response to prior hGH treatment.
- Participants with Turner syndrome known to have Y-chromosome material unless they have undergone gonadectomy and have fully external female genitalia.
- Diagnosis of systemic disease or condition that may cause short stature other than Turner syndrome, SHOX deficiency, or Noonan syndrome, eg, renal, neoplastic, pulmonary, cardiac, gastrointestinal, immunologic and metabolic disease.
- Bone age advanced beyond chronological age by more than 2 years.
- Congenital heart disease which places the participant at increased risk of an adverse cardiac outcome in the setting of hypotension,
- Have an unstable condition likely to require surgical intervention during the study.
- Evidence of decreased growth velocity (AGV < 1.5 cm/year) as assessed over a period of at least 6 months and growth plate closure assessed using bilateral lower extremity X-rays.
- Previous limb-lengthening surgery, or planned or expected to have limb lengthening surgery during the study period.
- Planned or expected bone-related surgery (ie, surgery involving disruption of bone cortex, excluding tooth extraction), during the study period.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vosoritide Dose 1 - Low Dose Vosoritide Injection Drug: Vosoritide - Dose 1 Injection • Experimental Drug Lyophilized powder for reconstitution Vosoritide Dose 2 - Medium Dose Vosoritide Injection Drug: Vosoritide - Dose 2 Injection • Experimental Drug Lyophilized powder for reconstitution Vosoritide Dose 3- High Dose Vosoritide Injection Drug: Vosoritide Dose 3 Injection • Experimental Drug Lyophilized powder for reconstitution Human Growth Hormone Human Growth Hormone Drug: Human Growth Hormone
- Primary Outcome Measures
Name Time Method Change from baseline in Annualized Growth Velocity (AGV) At 6 months
- Secondary Outcome Measures
Name Time Method Change from baseline in height Z-score At 6 months Change from baseline in height up to Final Adult Height (FAH) Every 6 months through the end of the study, up to 15 years Change from baseline in height Z-score up to FAH Every 6 months through the end of the study, up to 15 years Time vosoritide is present at maximum concentration (Tmax) Every 6 months through the end of the study, up to 15 years Change from baseline in Height 24 months Change in baseline height Z-score 24 months Change in baseline height in AGV 24 months Incidence of treatment-emergent adverse events Until the end of the study, up to 15 years Change from baseline in height At 6 months Change from baseline in lumbar spine bone mineral density (BMD) Z-score Every 12 months through the end of the study, up to 15 years Change from baseline in bone age/chronological age Every 12 months through the end of the study, up to 15 years Change from baseline in total body (less head) BMD Z-score Every 12 months through the end of the study, up to 15 years Maximum vosoritide observed plasma concentration (Cmax) Every 6 months through he end of the study, up to15 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 the 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 the study, up to 15 years Elimination half-life of vosoritide (t½) Every 6 months through the end of the study, up to 15 years Apparent clearance of vosoritide (CL/F) Every 6 months through the end of the study, up to 15 years Apparent volume of distribution of vosoritide (Vz/F) Every 6 months through the end of the study, up to 15 years Change from baseline on bone growth biomarkers Every 6 months through the end of the study, up to 15 years Change from baseline in urine cyclic guanine monophosphate (cGMP) Every 6 months through the end of the study, up to 15 years Change from baseline in serum collagen X marker (CXM) Every 6 months through the end of the study, up to 15 years Change from baseline in total body (less head) bone mineral content (BMC) Every 12 months through the end of the study, up to 15 years Change from baseline in lumbar spine BMC Every 12 months through the end of the study, up to 15 years
Trial Locations
- Locations (13)
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Nemours Children's Hospital, Delaware (Alfred I. Dupont Hospital for Children)
🇺🇸Wilmington, Delaware, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
St. Luke's Children's Endocrinology and Diabetes
🇺🇸Boise, Idaho, United States
Kentucky Children's Hospital
🇺🇸Lexington, Kentucky, United States
New York Medical College
🇺🇸Boston, Massachusetts, United States
M Health Fairview Pediatric Specialty Clinic - Explorer
🇺🇸Minneapolis, Minnesota, United States
Children's Hospital at Montefiore
🇺🇸Bronx, New York, United States
Atrium Health Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
University of Texas Health Science Center at Houston (UT Health)
🇺🇸Houston, Texas, United States
Angers University Hospital Center
🇫🇷Angers, Maine-et-Loire, France
CHU de Toulouse - Hôpital des Enfants
🇫🇷Toulouse, Occitanie, France
Central University Hospital of Asturias
🇪🇸Oviedo, Asturias, Spain